THE EFFECT OF LUMBAR SPINAL MANIPULATION UPON LOCAL … · iii Abstract Introduction: The mechanism for pain relief associated with spinal manipulation (SM) is not well understood

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This thesis is presented for the Honours degree in Science (Chiropractic) at Murdoch

University

THE EFFECT OF LUMBAR SPINAL MANIPULATION UPON LOCAL AND REMOTE

DEEP AND SUPERFICIAL PAIN PERCEPTION

Student Researcher

Dr Sasha Louise Dorron

B.Sc (Chiro), B.Chiro, PostgradCertBusAdmin (MasterClass)

Primary Supervisor

Dr Barrett Losco

Chiropractic Discipline, School of Health Professions, Murdoch University

Co-Supervisors

Professor Peter Drummond

Psychology Discipline, School of Psychology and Exercise Science, Murdoch University

Associate Professor Bruce Walker

Head of Chiropractic Discipline, School of Health Professions, Murdoch University

Submitted

November 2015

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I declare this thesis is my own account of my research and contains as its main content, work which

has not been previously submitted for a degree at any tertiary educational institution.

Dr Sasha Louise Dorron

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Abstract

Introduction: The mechanism for pain relief associated with spinal manipulation (SM) is not well

understood. Cervical SM decreases pressure sensitivity in the cervical spine and upper limb for at

least 10 minutes. Lumbar spine studies to date have demonstrated no effect.

Objectives: To determine whether lumbar SM has an effect on pressure pain threshold (PPT) and

pinprick sensitivity (PPS) at local and remote locations, the duration of any change, and whether

changes are related to the side of SM.

Methods: 34 asymptomatic participants, mean age 22.56 years (SD 3.99), were randomised to

receive a lumbar SM on the right or left side. PPT and PPS were measured bilaterally at the calf,

lumbar spine, scapula, and forehead at baseline, immediately post-SM, and after 10, 20, and 30

minutes. Effects of SM on PPT and PPS were investigated in repeated-measures ANOVAs.

Results: Calf and lumbar spine PPT increased bilaterally at 10, 20 and 30 minutes (7.2 - 11.8%

changes). PPS decreased in all locations at various times (9.8 – 22.5% changes). For the calf and

lumbar spine, increases in PPT tended to be greater on the side of SM compared to contralaterally,

although this varied over the follow-up period. Throughout the experiment, the left lumbar spine and

calf were more sensitive to pressure than the right, whereas the right calf and forehead were more

sensitive to pinprick than the left.

Conclusion: Lumbar SM appears to reduce pressure sensitivity locally and in the lower limb for at

least 30 minutes. These findings contradict prior lumbar spine studies, but are consistent with

cervical spine studies. The observed changes in pressure sensitivity may reflect local spinal or

complex supraspinal analgesic mechanisms. Pinprick sensitivity was reduced globally, and likely

represents a non-specific effect. However, a lack of control/sham limits the strength of the

conclusions.

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Table of Contents

1. Introduction .............................................................................................................................. 1

1.1. Topic and Purpose ....................................................................................................................... 2

1.2. Background on Spinal Manipulation ........................................................................................... 3

1.2.1. Force Time Characteristics of Spinal Manipulation ............................................................ 3

1.2.2. Clinical Application of Spinal Manipulation ........................................................................ 4

1.2.3. The Cavitation Phenomenon .............................................................................................. 4

1.3. Spinal Manipulation and Hypoalgesia ......................................................................................... 5

1.3.1. Pressure Pain Threshold ...................................................................................................... 7

1.3.1.1. Local Effects ................................................................................................................ 7

1.3.1.2. Remote Effects .......................................................................................................... 10

1.3.1.3. Sham-Controlled Studies .......................................................................................... 13

1.3.1.4. Asymmetric Effects ................................................................................................... 19

1.3.1.5. Other Factors ............................................................................................................ 19

1.3.2. Pinprick Sensitivity ............................................................................................................ 21

1.3.3. Thermal, Chemical, and Electrical Stimuli ......................................................................... 21

1.3.4. Biomechanical Factors ...................................................................................................... 22

1.3.5. Neurophysiological Factors ............................................................................................... 24

1.3.6. Biochemical Factors .......................................................................................................... 25

1.3.6.1. β-endorphins ............................................................................................................. 25

1.3.6.2. Substance P ............................................................................................................... 25

1.3.6.3. Cortisol ...................................................................................................................... 26

1.3.6.4. Other Biochemicals ................................................................................................... 27

1.3.7. Theories for Post-Manipulation Hypoalgesia.................................................................... 28

1.3.7.1. Descending Inhibitory Pain Control Theory .............................................................. 28

1.3.7.2. Pain Gate Theory....................................................................................................... 31

1.3.7.3. Altered Spinal Cord Dorsal Horn Excitability ............................................................ 31

1.3.7.4. Placebo and Psychosocial Factors ............................................................................. 32

1.4. State of the Literature ............................................................................................................... 32

2. Methods ................................................................................................................................. 33

2.1. Power Calculation ..................................................................................................................... 34

2.2. Participant Recruitment ............................................................................................................ 34

2.3. Randomisation .......................................................................................................................... 35

2.4. Procedure .................................................................................................................................. 35

2.5. Pressure Pain Threshold ............................................................................................................ 37

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2.6. Pinprick Sensitivity ..................................................................................................................... 38

2.7. Spinal Manipulation ................................................................................................................... 38

2.8. Data Analysis .............................................................................................................................. 39

3. Results ................................................................................................................................... 40

3.1. Algometer Standardisation ........................................................................................................ 40

3.2. Pain Sensitivity Results............................................................................................................... 40

3.2.1. Calf Pressure Pain Threshold ............................................................................................. 43

3.2.2. Lumbar Spine Pressure Pain Threshold ............................................................................. 45

3.2.3. Scapula Pressure Pain Threshold ....................................................................................... 47

3.2.4. Forehead Pressure Pain Threshold .................................................................................... 49

3.2.5. Calf Pinprick Sensitivity ...................................................................................................... 52

3.2.6. Lumbar Spine Pinprick Sensitivity ...................................................................................... 53

3.2.7. Scapula Pinprick Sensitivity................................................................................................ 55

3.2.8. Forehead Pinprick Sensitivity ............................................................................................. 56

3.2.9. Ipsilateral vs. Contralateral Changes ................................................................................. 58

4. Discussion .............................................................................................................................. 64

4.1. Baseline Characteristics ............................................................................................................. 64

4.2. Pressure Pain Threshold ............................................................................................................ 65

4.3. Pinprick Sensitivity ..................................................................................................................... 68

4.4. Interpretation ............................................................................................................................ 68

4.5. Limitations ................................................................................................................................. 71

5. Conclusion .............................................................................................................................. 72

References ............................................................................................................................. 74

Appendix A – Participant Checklist and Medical History Questionnaire .................................... 83

Appendix B – Information Letter ............................................................................................. 84

Appendix C – Consent Form .................................................................................................... 86

Appendix D – Shapiro-Wilk tests for Normality Results ............................................................ 87

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Acknowledgements

Firstly, I would like to express my sincere gratitude to my primary supervisor Dr Barrett Losco. His

continuous support, guidance, and patience have been priceless. Even amongst his very busy

schedule, he always had time for my unsolicited visits and endless questions. I could not have

imagined having a better advisor and mentor to ease me into the daunting world of research.

I would also like to sincerely thank my co-supervisor Professor Peter Drummond, for his willingness

to venture into something of a new area of study and his excellent statistics knowledge. His patience

in helping me learn the ins and outs of the stats was invaluable, as were his comments and attention

to detail.

I cannot forget my final co-supervisor Associate Professor Bruce Walker. A huge thanks go to him for

guiding me through many of the broader research concepts, giving me a good foundation for future

research. At times I struggled to see the forest for the trees, and he helped a great deal in widening

my perspective.

My thanks also go to Dr Norman Stomski and Dr Jeffrey Hebert for their help and advice in the

complicated world of statistics, to Dr Amanda Meyer and my dear friend Amy for their support in the

recruitment drive, and to Dr Gareth Calvert for being an understanding boss over the last two years.

Last but not least, a huge thank you to my fiancée Sam, my family, and my friends. For your

continuing support through this journey and in my grand plans for the future. For keeping me

grounded, coaxing me away from the keyboard, and making me laugh through it all. This would not

have been possible without you.

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List of Abbreviations

Abbreviations used in the following text are:

HVLA = high-velocity, low-amplitude

LBP = lower back pain

L-SM = group 2, receiving left L5-S1 spinal manipulation

MDC = minimum detectable change

NRS = numerical rating scale

PAG = periaqueductal gray

PPT = pressure pain threshold

PPS = pinprick sensitivity

R-SM = group 1, receiving right L5-S1 spinal manipulation

SM = spinal manipulation

SD = standard deviation

TSS = temporal sensory summation

Vertebral segments are described using the following paradigm:

C1 = first cervical vertebra (of seven)

T1 = first thoracic vertebra (of twelve)

L1 = first lumbar vertebra (of five)

C0-C1 = joint between occiput and first cervical vertebra

C5-C6 = joint between fifth and sixth cervical vertebrae

L5-S1 = joint between fifth lumbar vertebra and sacrum

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1. Introduction

Spinal manipulation (SM) is a manual therapy technique which is used within a number of health

care professions, particularly by chiropractors as well as osteopaths and physiotherapists

(Hurwitz 2012). It is primarily used in the treatment of musculoskeletal disorders including non-

specific lower back pain (LBP) and neck pain, among others. Current evidence supports the use

of SM in these scenarios, showing that it may be helpful in managing spinal pain and some types

of headache (Bronfort et al. 2012; Bryans et al. 2011; Giles and Muller 2003; Goertz et al. 2012;

Gross et al. 2010; Schneider et al. 2015). There is however a lack of evidence to explain the

physiological mechanism behind any positive clinical outcomes such as pain reduction. In

particular, this study is interested in further characterising hypoalgesia, or decreased pain

sensitivity, following SM. Gaining a better understanding of any hypoalgesia associated with SM

may improve its clinical application, allowing for practitioners to make better choices with

regard to when and where to apply SM.

Since SM is typically a regular component of the care delivered by a chiropractor (French et al.

2013), the topic of how SM exerts its clinical effects is a key area of research that could help

modernise the role of chiropractic in the health care arena. By facilitating greater understanding

of this technique the usefulness of SM may be better understood and applied with specificity

and improved clinical outcomes.

Improving our understanding of SM is an important area. LBP, for example, represents a

significant economic burden in Australia (Walker, Muller, and Grant 2003) and affects on

average 38% of people globally at some time (Hoy et al. 2012). Most cases of LBP are “non-

specific” or “mechanical” and thus conservative or non-invasive treatment options are most

appropriate (Cohen, Argoff, and Carragee 2009). Research into these conservative options,

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which includes SM, is of paramount importance in enabling health care providers to address

significant health concerns such as LBP from an evidence-based perspective.

1.1. Topic and Purpose

This study aims to investigate the effects of lumbar SM on local and remote pain sensitivity for

30 minutes following SM, as well as whether the effects are dependent on the side of SM.

The objective is to help fill significant gaps in our present knowledge surrounding the underlying

pain-relieving mechanisms of this modality. Specifically, the lumbar spine remains an area that

is understudied, with conflicting findings between the lumbar and cervical regions. The present

study will also investigate whether remote effects of SM on pain sensitivity are related to the

site of manipulation, or are global. The duration of changes to pain sensitivity following SM

beyond five to ten minutes is also a poorly studied topic, and thus this study will measure

changes up to 30 minutes following SM. The duration of changes to pain sensitivity is important

when considering the clinical value of SM.

In addition, it is unknown whether the effects of SM on pain sensitivity are dependent on which

side the SM is applied to. A greater understanding of this relationship may contribute to the

targeted use of SM in a clinical setting.

A novel measure of superficial pain sensitivity will be assessed alongside a more commonly

studied measure of deep pain sensitivity to enhance our understanding of the relationship

between SM and pain sensitivity.

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1.2. Background on Spinal Manipulation

There is significant variety in the specific SM techniques used by practitioners (Bergmann 2005).

High-velocity low-amplitude (HVLA) SM techniques are the most commonly utilised by

chiropractors, and involve a “quick thrust carried through a short distance” to a specific spinal

joint, using the practitioner’s hands (Bergmann 2005). Other techniques may variably utilise low-

force or non-thrust methods, or are delivered using instruments or other devices to assist

(Bergmann 2005). The bulk of the literature surrounding SM uses HVLA techniques, as does the

present study. As such, all future references to SM will refer specifically to HVLA SM, unless

specified.

It is theorised that the neurophysiological and clinical effects of different techniques may vary

(Bergmann 2005), though our understanding is limited at present. HVLA SM has unique

characteristics in terms of the forces applied to the spine, and the time over which these forces

are delivered. These are known as the force-time characteristics, and are discussed in section

1.2.1. The cavitation phenomenon frequently associated with SM is also discussed in section

1.2.3.

1.2.1. Force-Time Characteristics of Spinal Manipulation

An HVLA SM procedure has a distinct force-

time profile. It consists of a preload phase

followed by a rapid thrust phase where the

applied forces increase to a peak, which then

fall again after the thrust is completed

(Herzog 2010) (see Figure 1.1). In a review of

the topic by Herzog (2010), it is concluded

that preload and peak forces vary significantly by region. Peak forces are on average 400

Figure 1.1. HVLA spinal manipulation force-time characteristics.

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newtons in the lumbosacral region (Herzog 2010). There is also significant inter-practitioner

variation (Herzog 2010). Thrust times also vary, with lumbosacral HVLA SM thrusts being on

average 150 milliseconds (from the beginning of the thrust to the time of peak force) (Herzog

2010). Thus the mechanical stimulus applied to the spine during an HVLA SM varies depending

on the region and the practitioner.

1.2.2. Clinical Application of Spinal Manipulation

In a clinical setting, SM is typically performed on a suspected ‘dysfunctional’ spinal joint

(Bergmann and Peterson 2011). ‘Dysfunctional’ spinal joints are identified clinically using a

variety of patient history and physical examination factors (Walker and Buchbinder 1997). It is

anecdotally held that SM can restore the ‘dysfunctional’ segment to ‘normal’ (Bergmann and

Peterson 2011). It has however been shown that the identification of a ‘dysfunctional’ spinal

joint has quite poor inter-rater reliability (French, Green, and Forbes 2000).

In the following discussion, specific spinal vertebrae or joints will be described using the method

most commonly employed in chiropractic practice. “C1” would denote the first of seven cervical

vertebra, while “T1” and “L1” would denote the first (of twelve) thoracic and first (of five) lumbar

vertebrae respectively. “C5-C6” then describes specifically the joint between the fifth and sixth

cervical vertebrae. “C0” refers to the occiput (having a joint with the first cervical vertebra), and

“S1” refers to the sacrum.

1.2.3. The Cavitation Phenomenon

HVLA SM techniques are often associated with a ‘cracking’ or ‘popping’ noise heard by patients

and practitioners, called an audible release or cavitation (Bergmann 2005). This phenomenon is

believed to represent the sudden formation and collapse of a gas bubble within a facet joint

capsule following an SM procedure, as a result of altered intra-articular pressure (Bergmann

2005). This cavitation does not typically occur with non-HVLA techniques, but is sometimes

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heard during mobilisation procedures (Bergmann and Peterson 2011). It is unclear if the

occurrence of a cavitation is necessary to elicit clinical or physiological changes, but clinically it

is often used as a marker of the ‘success’ or ‘non-success’ of a SM procedure (Bergmann and

Peterson 2011). Most studies to date have found no difference in a variety of clinical or

physiological outcomes, whether a cavitation did or did not occur during a SM procedure

(Bialosky et al. 2010; Cleland et al. 2007; Flynn, Childs, and Fritz 2006; Flynn et al. 2003; Herzog

et al. 1995; Sillevis and Cleland 2011; Teodorczyk-Injeyan et al. 2008). Some studies have

however noted that an HVLA SM procedure that elicited a cavitation showed unique mechanical

properties or effects compared to procedures that did not elicit a cavitation (Cramer et al. 2012;

Gál et al. 1995). This suggests that SM procedures that elicit a cavitation may differ in their

mechanical effect on facet joints, but appear not to influence outcomes.

Several studies have revealed that HVLA SM may not be particularly accurate when comparing

where force is delivered and where cavitations occur, with around 50% accuracy depending on

the region of the spine (Dunning et al. 2013; Ross, Bereznick, and McGill 2004). We can surmise

from this that HVLA SM affects multiple facet joints in the broad vicinity around the target

segment (Cramer et al. 2011; Dunning et al. 2013; Ross, Bereznick, and McGill 2004).

1.3. Spinal Manipulation and Hypoalgesia

The majority of the literature investigating SM and hypoalgesia uses pressure pain threshold

(PPT) as the primary outcome measure. PPT is a form of experimentally-induced pain, and

represents the force required for mechanical pressure to elicit a nociceptive sensation.

Nociceptive signals are generated in response to potentially harmful stimuli (Mendell 2014).

Pinprick sensitivity (PPS) is another form of experimentally-induced pain, where a sharp stimulus

is applied to the skin and the resulting sensation subjectively measured.

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The nociceptive stimulus when measuring

PPT is generated by activating Aδ (small

diameter, thinly myelinated) and C (small

diameter, unmyelinated) sensory fibres

(Curatolo, Petersen-Felix, and Arendt-

Nielsen 2000; Julius and Basbaum 2001).

PPS is thought to be elicited through

stimulation of Aδ-fibres only (Curatolo,

Petersen-Felix, and Arendt-Nielsen 2000).

The afferent signals travel to lamina I and

V in the dorsal horn of the spinal cord and

ascend within the spinothalamic tract (Blumenfeld 2010) (see Figure 1.2). PPT (when measured

with a 1cm2 probe) appears to reflect sensitivity to deep mechanical stimulus, while PPS is a

measure of more superficial sensitivity (Takahashi et al. 2005).

There are a number of potentially confounding variables that affect pain sensitivity. It appears

that anxiety causes increased sensitivity to experimentally-induced pain, termed anxiety-

induced hyperalgesia (Martenson, Cetas, and Heinricher 2009; Rhudy and Meagher 2000). There

is a moderate to strong body of evidence to suggest that females have lower PPT compared to

males, while the effects of gender on PPS do not appear to have been studied (Fillingim et al.

2009; Racine et al. 2012). Many studies have also investigated the effects of the menstrual cycle

on experimental pain. The studies are conflicting, and at present no conclusion can be made

with regard to how PPT or PPS might be affected by the menstrual cycle (Fillingim et al. 2009;

Racine et al. 2012).

Figure 1.2. C-fibre and Aδ-fibre pathways.

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1.3.1. Pressure Pain Threshold

A recent systematic review by Coronado et al. (2012) included a meta-analysis on the effects of

SM on PPT. It was found that SM appeared to significantly increase PPT at sites remote to the

site of SM (the remote sites under investigation varied with each study), with an overall

favourable effect on increasing PPT compared to other interventions. The data from ten studies

was included in this meta-analysis, and the authors highlighted the paucity of quality literature

in this area. As such it is still a valuable area for future research. Seven further studies

investigating SM and PPT were identified which have been published in the interim (de Oliveira

et al. 2013; Fernández-Carnero, Cleland, and Arbizu 2011; Gay et al. 2014; Molina-Ortega et al.

2014; Orakifar et al. 2012; Packer et al. 2014; Srbely et al. 2013), and another which was

excluded from the review by Coronado et al. (2012) based on methodological factors (Suter and

McMorland 2002). It should be kept in mind that an increase in PPT represents a decrease in

pain sensitivity; an increased PPT means the participant was able tolerate more pressure before

feeling pain.

1.3.1.1. Local Effects

This section focuses on the effects of SM on PPT at locations within close anatomical vicinity

(local) to the site receiving SM, with the studies under discussion summarised in Table 1.1.

An early study with participants with chronic mechanical neck pain found that cervical SM

increased PPT at cervical paraspinal tender points when compared to cervical mobilisation,

measured five minutes after intervention (Vernon et al. 1990). The small sample size (N=9) limits

this study. More recently, Fernández-de-las-Peñas et al. (2008) studied asymptomatic

participants and found that cervical facet PPT increased following C7-T1 SM at five minutes,

which occurred bilaterally and was independent of the participant’s dominant side. This was in

comparison to a sham manipulative procedure, though each group only contained ten

participants. They also noted that male participants experienced greater increases in PPT than

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females. Molina-Ortega et al. (2014) demonstrated that C5-C6 SM in an asymptomatic

population lead to a significant immediate increase in PPT at the cervical musculature (and the

lateral elbow but not the calf), when compared with T4 SM and sham cervical SM. These changes

were not sustained at two hours, and again there were only ten participants per group. In a

study by Suter and McMorland (2002) in which all of the chronic neck pain participants received

C5-C6 or C6-C7 SM, PPT was noted to increase significantly in the cervical musculature

immediately post-SM. The study, however, lacks a comparator intervention or sham and thus

should be interpreted with caution. Maduro de Camargo et al. (2011) found that C5-C6 SM in

participants with mechanical neck pain resulted in increased PPT at the C5 spinous process and

the deltoid muscle, but not the upper trapezius muscle, compared to quiet rest. A study on

asymptomatic participants by Ruiz-Saez et al. (2007) found that upper trapezius muscle trigger

point PPT was increased five and ten minutes after a C3-C4 SM, when compared to sham SM.

Also in asymptomatic participants, Hamilton, Boswell, and Fryer (2007) found that bilateral C0-

C1 SM elicited a significant within-group increase in PPT at the midline suboccipital region at five

minutes but not at 30 minutes post-intervention. However, there were no significant differences

when compared to suboccipital muscle stretch and a sham manual technique. Fryer, Carub, and

Mclver (2004) compared upper thoracic SM to upper thoracic mobilisation and sham laser

acupuncture, in an asymptomatic population. The SM and mobilisation groups both showed an

immediate significant within-group increase in thoracic PPT. The mobilisation group, but not the

SM group, reached significance compared to the sham group. The study population was drawn

from osteopathic students thus a participant expectancy effect may have occurred, and a small

placebo effect was noted.

A study by Cote, Mior, and Vernon (1994) looked at PPT in a chronic LBP population following

lumbar SM compared to mobilisation. No significant changes in PPT were found in any location

(lumbar, sacroiliac or gluteal regions) immediately, 15 minutes or 30 minutes post-intervention,

compared to baseline and to mobilisation. Thomson, Haig, and Mansfield (2009) also

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investigated the effects of lumbar SM compared to mobilisation and sham laser acupuncture in

an asymptomatic population. PPT at the ‘most tender’ lumbar spinous process showed no

significant changes pre- and immediately post-intervention within any group or between groups.

There are several potential limitations with this study; as PPT appears to represent a measure

of deep pressure sensitivity (as discussed in section 1.3), PPT measured at a spinous process (a

bony landmark) may not provide reliable results due to the relative absence of deep soft tissue.

Difficulty with the algometer slipping off the spinous process has also been reported (Frank,

McLaughlin, and Vaughan 2013). The study also recruited participants from an osteopathic

student and teacher group, thus it may be subject to participant expectancy effects. A novel

study by de Oliveira et al. (2013) compared lumbar SM to upper thoracic SM in a chronic LBP

population. PPT was measured at the lumbar paraspinal and tibialis anterior muscles, with

lumbar PPT increasing significantly in the thoracic SM group only. It was noted by the authors

that the absolute change in PPT was small and may represent chance or measurement error.

Subjective pain intensity, however, decreased significantly in both groups. In a population of

asymptomatic females, Orakifar et al. (2012) found no changes to PPT at the sacroiliac joint

immediately or up to 15 minutes after sacroiliac joint SM. There was no comparison or placebo

group, and combined with the all-female participants mean these results should be interpreted

cautiously. In an interesting study by Gay et al. (2014), asymptomatic participants completed an

exercise protocol designed to induce LBP, and were then randomised to receive lumbar SM,

mobilisation, or therapeutic touch. There were no significant changes to PPT in any group when

tested at the lumbar paraspinal muscles, or the upper and lower limb. There was a statistically

significant decrease in pain intensity in all groups, which might represent the natural history of

exercise-induced LBP.

The above studies provide reasonable evidence that cervical SM leads to increases in local PPT.

In addition to the systematic review by Coronado et al. (2012), two further studies (as discussed)

support this conclusion (Molina-Ortega et al. 2014; Suter and McMorland 2002). The thoracic

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spine remains significantly under-studied, with only a single article finding that thoracic SM led

to increased local PPT. In the lumbar spine, the evidence from all identified studies indicates

that lumbar or lumbosacral SM does not lead to any changes in local PPT, though there are few

studies and they tend to be of poor quality. Given the differences in findings between the

cervical and lumbar regions, further studies are warranted to investigate if these apparent

differences are accurate, and why this might be so.

1.3.1.2. Remote Effects

This section focuses on the effects of SM on PPT at locations remote to or separate from the site

receiving SM. See Table 1.2 for a summary of these studies. The neurological relationship

between the site receiving SM and the site/s where PPT is measured are described in each case,

in order to note whether there is a direct neurological link between the two. For example, a

direct or ‘segmental’ link is considered present if spinal nerve roots at or close to the site of SM

innervate structures at the site where PPT is measured (e.g. skin or muscle). This is potentially

important when considering the mechanism behind post-SM hypoalgesia, and whether any

hypoalgesia is regional or global.

The study by Maduro de Camargo et al. (2011) found that C5-C6 SM in mechanical neck pain

participants led to an increase in PPT at the C5 spinous process and deltoid muscle bilaterally at

five minutes, compared to control, though no significant changes in PPT at the upper trapezius

muscle were found. Both the deltoid and upper trapezius muscles are segmentally linked the

C5-C6 region. Srbely et al. (2013) compared PPT findings following bilateral C5-C6 SM or sham

cervical SM at myofascial trigger points in the right infraspinatus muscles (segmentally linked via

the C5 and C6 nerve roots) and gluteus medius muscles (segmentally unrelated). Significant

increases in PPT were observed for at least 15 minutes at the infraspinatus muscle after SM

compared to sham, with no changes in gluteus medius PPT.

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Two studies with similar protocols measured changes in PPT at the lateral epicondyle (within

the C6 dermatome) immediately before and after C5-C6 level SM, compared to sham/control.

One recruited asymptomatic participants (Fernández-de-las-Peñas et al. 2007), and the other

used participants with lateral epicondylalgia (lateral elbow pain) (Fernández-Carnero,

Fernández-de-las-Peñas, and Cleland 2008), each employing a cross-over design with 15 and 10

participants respectively. Both found significant bilateral increases in PPT at the lateral

epicondyle in the SM groups compared to sham/control. Another very similar study by

Fernández-Carnero, Cleland, and Arbizu (2011) compared the effects of C5-C6 SM to mid-

thoracic SM on PPT over the lateral epicondyle (segmentally linked to the cervical but not mid-

thoracic spine), in 18 participants with lateral epicondylalgia. Cervical SM was found to

significantly increase PPT bilaterally while thoracic SM did not. The study by Molina-Ortega et

al. (2014) noted that PPT in the cervical spine and lateral elbow (segmentally linked to C5 and

C6) increased, but there was no change at the tibialis anterior muscle (segmentally unrelated to

the cervical or thoracic spine). This was following C5-C6 SM in asymptomatic participants, when

compared to upper thoracic SM and sham.

Bishop, Beneciuk, and George (2011) studied changes to PPT in the web spaces of the first and

second fingers, and first and second toes, following upper thoracic SM in an asymptomatic

population. No significant differences in PPT were identified at either location in the SM group,

compared to a cervical exercise group and control. The lower limb testing site is segmentally

unrelated to the upper thoracic spine. The upper limb testing site is situated within the C6

dermatome, and is anatomically overlying the first dorsal interosseus and adductor pollicis

muscles (though this was not specifically identified), which are innervated by the C8 and T1

nerve roots. The thoracic manipulation technique used was a supine manoeuvre that was

theorised by Bishop, Beneciuk, and George (2011) to affect the upper thoracic and lower cervical

regions. It is possible, however, that the technique exerted its main effect below these levels.

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The study by de Oliveira et al. (2013) found no change to PPT at the tibialis anterior muscle

following lumbar SM (segmentally linked via the L5 nerve root). Gay et al. (2014) demonstrated

no changes to PPT in the lumbar spine, or the web spaces of the first and second fingers

(segmentally unrelated), and first and second toes (segmentally related via L5 and S1 nerve

roots), after lumbar SM, mobilisation or therapeutic touch in participants with exercise-induced

LBP. Subjective pain intensity did improve in all groups.

Interestingly, a study by Oliveira-Campelo et al. (2010) found that C0-C1 SM in asymptomatic

individuals led to increases in PPT in the masseter muscles compared to both soft tissue therapy

and control. Significant increases in PPT at the temporalis muscles occurred in both the SM and

soft tissue therapy groups compared to control. This is further supported by the findings of

Mansilla-Ferragut et al. (2009), where increases in PPT over the sphenoid bone bilaterally were

observed five minutes following bilateral C0-C1 SM, in a female population with mechanical neck

pain. It was speculated that this effect is mediated by the trigemino-cervical nucleus caudalis,

which extends into the upper cervical spinal cord (Blumenfeld 2010). A study by Packer et al.

(2014) investigated PPT in the masseter and temporalis muscles and at the temporomandibular

joint, as well as subjective pain intensity, in female participants with temporomandibular

disorders. Participants received a single session of upper thoracic SM. No significant changes to

PPT or pain intensity were observed, which may be explained by the absence of a direct

segmental link between the upper thoracic spine and trigeminal nerve.

The studies investigating cervical SM support the conclusions of Coronado et al. (2012), including

three since the review (Fernández-Carnero, Cleland, and Arbizu 2011; Molina-Ortega et al. 2014;

Srbely et al. 2013). There appears to be moderate evidence of at least a short term increase in

PPT in locations with a segmental neurological link to the site of cervical SM (the upper limb and

jaw/head). The conclusions from two lumbar spine studies suggest that lumbar SM does not

lead to a segmental change in PPT (i.e. in the lower limb). Just as for local hypoalgesia, the topic

13

of remote hypoalgesia following lumbar SM is significantly understudied. Considering the

conflicting evidence with the cervical spine, further research to clarify this topic is important. No

studies were identified that suggest SM might have a non-segmental or global effect on PPT.

1.3.1.3. Sham-Controlled Studies

When considering just the sham-controlled studies, there is significant support for a mechanical

hypoalgesic effect in the cervical spine and upper limb following cervical SM over sham

(Fernández-Carnero, Fernández-de-las-Peñas, and Cleland 2008; Fernández-de-las-Peñas et al.

2008; Fernández-de-las-Peñas et al. 2007; Molina-Ortega et al. 2014; Ruiz-Saez et al. 2007;

Srbely et al. 2013). Only a single study found an increase in cervical spine PPT in all groups

including cervical SM and sham (Hamilton, Boswell, and Fryer 2007). Mansilla-Ferragut et al.

(2009) demonstrated an increase in PPT over the sphenoid bone after cervical SM but not sham,

and Packer et al. (2014) found no change in PPT at the jaw after thoracic SM compared to sham.

One study noted local mechanical hypoalgesia in the thoracic spine following thoracic SM but

not sham, though the effect appeared to be equivalent to or less than after thoracic mobilisation

(Fryer, Carub, and Mclver 2004). Two studies in the lumbar region indicate the absence of a local

or remote mechanical hypoalgesic effect following lumbar SM, mobilisation and sham (Gay et

al. 2014; Thomson, Haig, and Mansfield 2009).

Overall, it appears that a mechanical hypoalgesic effect occurs in the cervical spine and upper

limb, and possibly the head, following cervical SM, and may occur in the thoracic spine after

thoracic SM. The lumbar spine or lower limb does not appear to develop mechanical hypoalgesia

in response to lumbar SM.

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Table 1.1. Summary of studies for local effects of spinal manipulation on PPT.

Reference Participants Intervention/s Outcome Measures Main Findings

(Vernon et al. 1990) N=9 (6 male) Chronic mechanical neck pain, mean age 38yrs

Participants randomised to either: 1) Cervical HVLA SM 2) Cervical mobilisation

PPT bilaterally at cervical paraspinal muscles. Measured baseline and 5min post-intervention.

Significant increase in PPT bilaterally in the SM group compared to mobilisation.

(Fernández-de-las-Peñas et al. 2008)

N=30 (13 male) Asymptomatic, right-hand dominant, mean age 26yrs

Participants randomised to one of: 1) Right C7-T1 HVLA SM 2) Left C7-T1 HVLA SM 3) Sham, simulated C7-T1 SM without tension or thrust

PPT bilaterally at C5-C6 joint. Measured baseline and 5min post-intervention.

Significant increase in PPT bilaterally in both SM groups compared to sham.

(Molina-Ortega et al. 2014)

N=30 (16 male) Asymptomatic, mean age 25.8-29.8yrs

Participants randomised to one of: 1) Right or left C5-C6 HVLA SM 2) T4 HVLA SM 3) Sham, simulated C5-C6 SM without tension or thrust

PPT bilaterally at the C5-C6 joint, lateral epicondyle, and tibialis anterior muscles. Serum substance P and nitric oxide concentrations. Measured baseline, and immediately and 2hrs post-intervention.

Significant increase in PPT bilaterally at C5-C6 and lateral epicondyle in cervical SM group immediately but not at 2hrs, compared to other groups. No change to tibialis anterior PPT. Significant increase in substance P in cervical SM group compared to other groups.

(Suter and McMorland 2002)

N=16 (2 male) Chronic neck pain, mean age 33.8yrs

All participants received: 1) Right or left C5-C6 or C6-C7 HVLA SM

PPT bilaterally at upper trapezius, sternocleidomastoid and mid-cervical muscles. Cervical range of motion, subjective pain intensity, and biceps muscle inhibition and force. Measured baseline and immediately post-intervention.

Significant increase in PPT at all sites. Significant increase in range of motion. Significant bilateral decrease in biceps muscle inhibition and increase in force.

(Maduro de Camargo et al. 2011)

N=37 (21 male) Mechanical neck pain, mean age 30yrs

Participants randomised to either: 1) Right-sided C5-C6 HVLA SM 2) Control, sitting, 2min of quiet rest

PPT bilaterally at upper trapezius and deltoid muscles, and C5 spinous process. Electromyographic data of deltoid muscles during different contractions. Measured baseline and 5min post-intervention.

Significant increase in PPT at deltoid and C5 spinous process in the SM group only. Significant increase in EMG amplitude and fatigue resistance in deltoid muscle during 30sec isometric contraction.

(Ruiz-Saez et al. 2007) N=72 (27 male) MTrPs in upper trapezius and C3-C4 facet joint dysfunction, mean age 31yrs

Participants randomised to either: 1) Right or left C3-C4 HVLA SM 2) Sham, simulated C3-C4 SM without tension or thrust

PPT at upper trapezius muscle MTrP on the side of SM. Measured baseline, and at 1min, 5min, and 10min post-intervention.

Trend toward increase in PPT in SM group only at all time points, not statistically significant. Significant decrease in PPT in sham group at 5min and 10min.

15


(Hamilton, Boswell, and Fryer 2007)

N=90 (29 male) Asymptomatic, mean age 23yrs

Participants randomised to one of: 1) Bilateral C0-C1 HVLA SM 2) Bilateral muscle-energy technique suboccipital muscle stretch 3) Sham, ‘subtle positioning of the upper neck’, held for 30sec, no ‘barrier was engaged’

PPT at midline suboccipital region. Measured baseline, and at 5min and 30min post-intervention.

Significant increase in PPT across entire cohort, no significant between-group differences.

(Fryer, Carub, and Mclver 2004)

N=96 (39 male) Asymptomatic, osteopathic students, age 19-34yrs

Participants randomised to one of: 1) HVLA SM to ‘most tender’ thoracic joint 2) 30sec extension mobilisation to ‘most tender’ thoracic joint 3) Sham, simulated laser acupuncture to ‘most tender’ thoracic joint

PPT at ‘most tender’ thoracic spinous process. Measured baseline and immediately post-intervention.

Significant increase in PPT in both experimental groups pre- and post- intervention. Significant increase in PPT in the mobilisation group, but not the SM group, compared to sham.

(Cote, Mior, and Vernon 1994)

N=39 (6 male) Chronic mechanical LBP, mean age 31yrs

Participants randomised to either: 1) Lumbar SM 2) Supine lumbar mobilisation

PPT at the ipsilateral lumbar paraspinal muscles, gluteal muscle and sacroiliac joint. Measured baseline, and immediately, 15min, and 30min post-intervention.

No significant changes to PPT in either group.

(Thomson, Haig, and Mansfield 2009)

N=50 (29 male) Asymptomatic, osteopathic college students/staff, mean age 27yrs

Participants randomised to one of: 1) Right-sided HVLA SM to ‘most tender’ lumbar joint 2) 30sec right-sided mobilisation to ‘most tender’ lumbar joint 3) Sham, 30sec simulated laser acupuncture to ‘most tender’ lumbar joint

PPT at the ‘most tender’ lumbar spinous process. Measured baseline and immediately post-intervention.

No significant changes to PPT in any group.

(de Oliveira et al. 2013) N=148 (39 male) Chronic non-specific LBP, mean age 46yrs

Participants randomised to either: 1) Upper thoracic HVLA SM 2) Lumbar HVLA SM

PPT bilaterally at the L3 and L5 paraspinal muscles and tibialis anterior muscle. Subjective pain intensity. Measured baseline and immediately post-intervention.

Significant increase in PPT at all lumbar levels within the thoracic SM group only, but no significant between-group differences. Pain intensity decreased significantly in both groups.

(Orakifar et al. 2012) N=20 (0 male) Asymptomatic, age 18-30yrs

All participants received: 1) Right-sided sacroiliac joint HVLA SM

PPT at the posterior superior iliac spine. Hoffman reflex at the tibial nerve. Measured baseline, and at 1min, 5min, 10min and 15min post-intervention.

No significant change to PPT. Significant transient attenuation of Hoffman reflex.

16


(Gay et al. 2014) N=24 (17 male) Asymptomatic, mean age 21.6yrs

Participants completed exercise protocol to induce LBP, then randomised to receive one of: 1) Lumbar HVLA SM 2) Lumbar mobilisation 3) Therapeutic touch to the lumbosacral region

PPT bilaterally at the L1, L5, and S2 paraspinal muscles, and at the dorsal web space of 1st and 2nd fingers and 1st and 2nd toes. Brain functional connectivity using MRI. Subjective pain intensity. Measured baseline and immediately post-intervention.

No significant changes to PPT occurred in any group. Various significant changes in functional connectivity occurred. Significant decrease in subjective pain intensity in all groups.

Abbreviations: HVLA = high-velocity low-amplitude, LBP = lower back pain, PPT = pressure pain threshold, SM = spinal manipulation.

Table 1.2. Summary of studies for remote effects of spinal manipulation on PPT.


(Maduro de Camargo et al. 2011)


Participants randomised to either: 1) Right-sided C5-C6 HVLA SM 2) Control, sitting, 2min of quiet rest

PPT bilaterally at upper trapezius and deltoid muscles, and C5 spinous process. Electromyographic data of deltoid muscles during different contractions. Measured baseline and 5min post-intervention.

Significant increase in PPT at deltoid and C5 spinous process in the SM group only. Significant increase in EMG amplitude and fatigue resistance in deltoid muscle during 30sec isometric contraction.

(Srbely et al. 2013) N=36 (19 male) MTrPs in right infra-spinatus and gluteus medius muscles, mean age 28yrs

Participants randomised to either: 1) Bilateral C5-C6 HVLA SM 2) Sham, simulated C5-C6 SM with similar pre-load forces but inert thrust

PPT at right infraspinatus and gluteus medius muscle MTrPs. Measured baseline, and at 1min, 5min, 10min, and 15min post-intervention.

Significant increase in PPT at the infraspinatus muscle in the SM group compared to the gluteus medius muscle and to sham.

(Fernández-de-las-Peñas et al. 2007)

N=15 (7 male) Asymptomatic, mean age 21yrs

Participants received each, on 3 separate days >48hrs apart: 1) Right or left C5-C6 HVLA SM 2) Placebo, simulated C5-C6 SM without tension or thrust 3) Control, active cervical lateral flexion and rotation (no therapist contact)

PPT bilaterally at the lateral epicondyle. Measured baseline and 5min post-intervention.

Significant increase in PPT at both elbows in the SM group compared to placebo and control groups.

17


(Fernández-Carnero, Fernández-de-las-Peñas, and Cleland 2008)

N=10 (5 male) Right-sided lateral elbow pain, mean age 42yrs

Participants received each, on 2 separate days >48hrs apart: 1) Right-sided C5-C6 HVLA SM 2) Manual contact intervention, simulated C5-C6 SM without tension or thrust

PPT bilaterally at the lateral epicondyle. Hot and cold pain thresholds bilaterally at the lateral epicondyle. Pain-free grip force on the symptomatic side and maximum grip force on the unaffected side. Measured baseline and 5min post-intervention.

Significant increase in PPT bilaterally in the SM group compared to manual contact. No significant changes for hot or cold pain thresholds. Significant increase in pain-free grip force in the SM group compared to manual contact.

(Fernández-Carnero, Cleland, and Arbizu 2011)

N=18 (8 male) Right-sided lateral elbow pain, mean age 44.8yrs

Participants randomised to either: 1) Right-sided C5-C6 HVLA SM 2) HVLA SM to the T5-T8 region

PPT bilaterally at the lateral epicondyle. Pain-free grip strength on symptomatic side and maximum voluntary grip strength on the unaffected side. Measured baseline and 5min post-intervention.

Significant increase in PPT bilaterally in the cervical SM group compared to thoracic SM. Significant increase in pain-free grip strength in both groups.

(Molina-Ortega et al. 2014)

N=30 (16 male) Asymptomatic, mean age 25.8-29.8yrs

Participants randomised to one of: 1) Right or left C5-C6 HVLA SM 2) T4 HVLA SM 3) Control, simulated C5-C6 SM without tension or thrust

PPT bilaterally at the C5-C6 joint, lateral epicondyle, and tibialis anterior muscles. Serum substance P and nitric oxide concentrations. Measured baseline, and immediately and 2hrs post-intervention.

Significant increase in PPT bilaterally at C5-C6 and lateral epicondyle in cervical SM group immediately but not at 2hrs, compared to other groups. No change to tibialis anterior PPT. Significant increase in substance P in cervical SM group compared to other groups.

(Bishop, Beneciuk, and George 2011)

N=90 (24 male) Asymptomatic, mean age 22.9yrs

Participants randomised to one of: 1) HVLA SM to upper thoracic region 2) ‘Chin tuck’ cervical exercise 3) Control, supine, 5min quiet rest

PPT bilaterally at dorsal web space of 1st and 2nd fingers and 1st and 2nd toes. Thermal ‘first pain’ sensitivity bilaterally at the anterior forearm and posterior upper calf. Temporal sensory summation bilaterally at the thenar eminence and dorsal foot. Measured baseline and immediately post-intervention.

PPT increased significantly within all groups. No significant changes in PPT between groups. No significant changes in thermal ‘first pain’ between groups. Significant decrease in temporal sensory summation in the SM group compared to the exercise and control groups.

(de Oliveira et al. 2013) N=148 (39 male) Chronic non-specific LBP, mean age 46yrs

Participants randomised to either: 1) Upper thoracic HVLA SM 2) Lumbar HVLA SM

PPT bilaterally at the L3 and L5 paraspinal muscles and tibialis anterior muscle. Subjective pain intensity. Measured baseline and immediately post-intervention.

Significant increase in PPT at all lumbar levels within the thoracic SM group only, but no significant between-group differences. Pain intensity decreased significantly in both groups.

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(Gay et al. 2014) N=24 (17 male) Asymptomatic, mean age 21.6yrs

Participants completed exercise protocol to induce LBP, then randomised to receive one of: 1) Lumbar HVLA SM 2) Lumbar mobilisation 3) Therapeutic touch to the lumbosacral region

PPT bilaterally at the L1, L5, and S2 paraspinal muscles, and at the dorsal web space of 1st and 2nd fingers and 1st and 2nd toes. Brain functional connectivity using MRI. Subjective pain intensity. Measured baseline and immediately post-intervention.

No significant changes to PPT occurred in any group. Various significant changes in functional connectivity occurred. Statistically significant decrease in subjective pain intensity in all groups.

(Oliveira-Campelo et al. 2010)

N=122 (31 male) MTrPs in the masseter muscle, mean age 20yrs

Participants randomised to one of: 1) Bilateral C0-C1 HVLA SM 2) Soft tissue therapy to suboccipital muscles 3) Control, supine, 2min quiet rest

PPT bilaterally at MTrPs in the masseter and temporalis muscles. Active mouth opening in millimetres. Measured baseline and 2min post-intervention.

Significant increase in PPT at masseter muscles in SM group compared to soft tissue therapy and control. Significant increase in PPT at temporalis muscles in SM and soft tissue therapy groups compared to control. Significant increase in active mouth opening in SM group compared to others.

(Mansilla-Ferragut et al. 2009)


Participants randomised to either: 1) Bilateral C0-C1 HVLA SM 2) Placebo, simulated C0-C1 SM with full passive cervical rotation

PPT bilaterally at the sphenoid bone. Pain-free maximal mouth opening in millimetres. Measured baseline and 5min post-intervention.

Statistically significant increase in PPT and in maximal mouth opening in the SM group compared to placebo.

(Packer et al. 2014) N=32 (0 male) Temporomandibular pain and neck pain, mean age 23.5-26yrs

Participants randomised to either: 1) T1 HVLA SM 2) Placebo, simulated T1 SM without tension or thrust

PPT bilaterally at masseter and temporalis muscles and the temporomandibular joint. Subjective pain intensity. Measured baseline, immediately post-intervention, and 48-72hrs post-intervention.

No statistically significant changes seen in either group for any outcome measure.

Abbreviations: HVLA = high-velocity low-amplitude, LBP = lower back pain, PPT = pressure pain threshold SM = spinal manipulation.

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1.3.1.4. Asymmetric Effects

A limited number of studies specifically investigate whether SM causes changes to PPT that are

bilateral, asymmetrical, or unilateral. Each of the studies found increases in PPT were bilateral

(Fernández-Carnero, Cleland, and Arbizu 2011; Fernández-Carnero, Fernández-de-las-Peñas,

and Cleland 2008; Fernández-de-las-Peñas et al. 2008; Fernández-de-las-Peñas et al. 2007;

Maduro de Camargo et al. 2011). Three of these studies found that PPT increased more on the

ipsilateral side following right cervical SM, though all participants were right-hand dominant

(Fernández-Carnero, Cleland, and Arbizu 2011; Fernández-Carnero, Fernández-de-las-Peñas,

and Cleland 2008; Maduro de Camargo et al. 2011). Fernández-de-las-Peñas et al. (2008) and

Fernández-de-las-Peñas et al. (2007) found that right PPT increased more than left in right-hand

dominant participants, regardless of which side of the cervical spine was manipulated. The

evidence thus suggests that SM affects PPT bilaterally, but there may be asymmetry related to

the participant’s dominant side, the side of SM, or another unknown factor. No studies have

directly compared right- to left-hand dominant participants. As these articles involve only

cervical SM, no assumptions can be made about whether such effects also occur in the lumbar

spine.

1.3.1.5. Other Factors

Overall, the duration of changes in PPT remains unclear. Few studies assessed short-term PPT

changes beyond ten minutes. One found increases in PPT that were present at five minutes but

not at 30 minutes (Hamilton, Boswell, and Fryer 2007), and another found changes that

persisted to 15 minutes but did not measure beyond this (Srbely et al. 2013). Another study

identified PPT changes immediately but not two hours post-SM (Molina-Ortega et al. 2014).

Three further studies measured beyond ten minutes, but failed to find changes in PPT at any

time point (Cote, Mior, and Vernon 1994; Orakifar et al. 2012; Packer et al. 2014). The study by

Schiller (2001) applied up to six interventions of thoracic SM over a three week period, in

participants with mechanical thoracic spine pain. It was found that PPT in the thoracic spine (the

20

specific location is not identified) increased at the final treatment and at follow-up one month

later compared to baseline, but not compared to sham ultrasound. However, the study is at risk

of committing type II error (falsely accepting a null hypothesis) due to low power. Shearar,

Colloca, and White (2005) compared four sessions of sacroiliac joint HVLA SM or mechanical

sacroiliac joint SM over two weeks in a population with sacroiliac joint syndrome. PPT at the

sacroiliac joints showed no changes in either group when measured before the third treatment

visit, or at the follow-up visit within one week of the final treatment. Any short-term changes in

PPT would have been missed. A variety of subjective measures improved significantly in both

groups. Thus we have no clear evidence regarding how long changes in PPT might last for, and

there is a definite need to investigate this systematically.

Based on the current literature, it is unclear if the magnitude or duration of PPT changes are

dose related as this specific relationship does not appear to have been studied. Importantly, the

clinical implications of the observed increases in PPT following SM is limited at this stage as no

studies correlate changes in PPT to changes in clinical outcomes. However, it is tempting to

hypothesise that mechanisms that result in increases in PPT may cause part or all of the

subjective pain relief associated with SM. This relationship needs further investigation.

The studies discussed variably use asymptomatic or symptomatic populations. No literature was

identified comparing the effects of SM on PPT between asymptomatic and symptomatic

populations. It is possible that there are differences in the responses of these two groups based

on pain sensitisation mechanisms and is an area for future research.

The majority of the above studies use the occurrence of a cavitation during the SM procedure

as an indicator of success. If a cavitation is not heard, a second attempt is typically performed.

As discussed in section 1.2.3, it appears that a cavitation is not a necessary element of a

successful SM procedure.

21

1.3.2. Pinprick Sensitivity

No studies were identified that assessed changes to PPS following SM. As such this is a novel

and potentially valuable topic for future research.

1.3.3. Thermal, Chemical, and Electrical Pain Stimuli

There are a number of studies that assess other measures of pain sensitivity following SM,

including thermal, chemical and electrical stimulus thresholds, summarised by Coronado et al.

(2012). This topic also lacks robustness in the literature.

The effect of SM on thermal sensitivity has been investigated in a few studies. An immediate

reduction in thermal sensitivity has been observed in the leg but not the arm following lumbar

HVLA SM in LBP (Bialosky et al. 2009b) and asymptomatic (Bialosky et al. 2008; George et al.

2006) participants, when compared to exercise interventions. The same has also been observed

in both the upper and lower limb immediately following upper thoracic HVLA SM but not

exercise or rest in 90 healthy individuals (Bishop, Beneciuk, and George 2011). All four of these

studies specifically found that temporal sensory summation (TSS) was reduced, thought to be

mediated by C-fibre pathways, but found no changes to thermal pain thresholds, thought to be

mediated by Aδ-fibre pathways (Anderson et al. 2013; Weiss et al. 2008). TSS is believed to

represent a measure of the wind-up phenomenon, where repetitive nociceptive stimulation

leads to excitation of the dorsal horn, which may be involved in central sensitisation (Anderson

et al. 2013). The findings of Fernández-Carnero, Fernández-de-las-Peñas, and Cleland (2008) are

in line with this pattern, showing no change to thermal pain thresholds following cervical HVLA

SM in participants with lateral epicondylalgia. TSS was not tested in this study. As increased TSS

has been observed in several chronic pain conditions compared to healthy populations

(Anderson et al. 2013), the finding that TSS appears to be reduced following SM has implications

for the treatment of chronic pain conditions that deserve investigation. Only one of the above

studies looked at TSS in a symptomatic population, LBP sufferers with an average symptom

22

duration of 222 weeks (Bialosky et al. 2009b). Future research in this area should investigate

different populations, and whether there is a correlation between changes to TSS and clinical

outcomes following SM.

Other experimental pain stimuli have also been investigated. Mohammadian et al. (2004) is the

only study identified which has taken a preliminary look at chemically-induced pain, using

capsaicin cream on the forearm. The group that received cervical SM exhibited immediate

reductions in the size of the area (which was exposed to capsaicin cream) experiencing allodynia,

or pain in response to a stimulus that should not be painful, and hyperalgesia, an excessive pain

response, as well as the intensity of spontaneous pain compared to the control group. In

addition, an increase in electrical pain tolerance has been noted in a population of 50

chiropractic students, for ten minutes following thoracic SM, compared to controls (Terrett and

Vernon 1984).

These studies provide preliminary evidence that SM not only results in mechanical hypoalgesia,

but possibly also hypoalgesia to thermal, chemical and electrical stimuli. More research in this

area is needed.

1.3.4. Biomechanical Factors

SM is essentially a mechanical impulse applied to the spine, with resulting biomechanical effects

on the body (Triano 2005). Thus it is generally accepted that part of the therapeutic benefit of

SM arises from the biomechanical impact (Triano 2005). Our understanding to date of the

biomechanical impacts of SM is limited, but forms an important element in our understanding

of how SM achieves clinical results.

It has been found that both HVLA and mechanical SM result in significant displacement or

translation of the spinal segment being targeted, as well as of the adjacent segments (Colloca,

23

Keller, and Gunzburg 2004; Colloca et al. 2006; Gál et al. 1994a, b, 1997; Keller, Colloca, and

Gunzburg 2003). Several studies using mechanical SM also found that this vertebral

displacement was temporally related to the initiation of action potentials, recorded in the dorsal

horn of the targeted segment (Colloca, Keller, and Gunzburg 2003, 2004; Colloca et al. 2000).

It has been hypothesised that stretch of the facet joint capsule and surrounding structures

occurs during a SM procedure (Pickar 2002). We know that facet joint capsules are innervated

with a variety of low- and high-threshold mechanoreceptors and some nociceptors, and that

capsule stretch within the physiologic range stimulates mechanoreceptors (Lu et al. 2005;

McLain and Raiszadeh 1995). Beyond the physiologic range nociceptive signals become

prevalent (Lu et al. 2005; McLain and Raiszadeh 1995). It has been documented in human

cadaver studies that mechanical lumbar SM does strain the facet joint capsule at the site and

distal to the site of manipulation (Ianuzzi and Khalsa 2005a, b). The capsule strain does not

exceed that noted during normal physiological movements, though the particular characteristics

of the strain and loading that occur during SM are suggested to trigger novel, non-physiologic

afferent stimulation (Ianuzzi and Khalsa 2005a). A study using a feline model found that different

directions of SM loading produced somewhat unique responses in lumbar facet capsule

mechanoreceptors, lending strength to this theory (Pickar and McLain 1995). Further studies in

feline models have shown that muscle spindle responses occur following mechanical SM, and

that the responses to rapid loading (like those during HVLA SM) are greater than responses

during slower loading (Pickar and Kang 2006; Pickar et al. 2007). This was further characterised

in humans, with the finding that faster thrust speeds led to greater thoracic paraspinal muscle

electromyographic activity (Pagé et al. 2014). This evidence supports the notion that facet

capsule and paraspinal muscle stretch does occur during SM, and that the mechanical

characteristics of SM may lead to unique afferent signals. This unique input to the nervous

system may help to account for some of the clinical and physiological effects associated with

SM, including hypoalgesia.

24

1.3.5. Neurophysiological Factors

A variety of studies have investigated the effects of SM on neurophysiology by specifically

observing changes to central nervous system functions and processing. This is a broad area, and

the research at present is very limited in scope and applicability, but is highly interesting

nonetheless.

Reed et al. (2014) found, in rats which received mechanical lumbar SM, that a higher thrust

magnitude resulted in an increase in the threshold of nociceptive lateral thalamic neurons to

mechanical stimuli (i.e. decreased sensitivity). A smaller-magnitude thrust resulted in no change.

The lateral thalamic nuclei are responsible for relaying and integrating sensory information as it

ascends to the cortex and other regions of the brain (Patestas and Gartner 2006). It also appears

to have a relationship with descending pain control circuits, as discussed in section 1.3.7.1. Thus

it is interesting to consider that a sufficient mechanical stimulus to the spine may affect the

sensitivity of nociception processing in the thalamus. This warrants further research in human

subjects, and may help in our currently limited understanding of how SM results in hypoalgesia.

There is some early experimental evidence that suggests SM could possibly have an effect on

aspects of central pain and the processing and integration of sensory information. A variety of

intra- and inter-hemispheric changes to functional connectivity between regions of the brain

involved in pain processing have been observed following lumbar SM, mobilisation, and

therapeutic touch interventions (Gay et al. 2014). Some changes were unique to each

intervention, while others were common to all groups and may represent natural history or

effects shared by the three manual therapies. This study was previously described as it also

measured PPT and pain scores; PPT did not change in any group but pain scores improved in all

groups. It is suggested by the authors that the intervention-dependent changes to functional

connectivity may help elucidate the mechanisms of pain relief associated with the interventions,

though this is highly speculative.

25

1.3.6. Biochemical Factors

In an attempt to determine the mechanism behind the hypoalgesia associated with SM, the

effects of SM on various pain-related biochemicals have been investigated.

1.3.6.1. -endorphins

A number of studies have measured changes to serum -endorphin levels following SM. -

endorphins are endogenous opioids with a potent pain-relieving function, acting to inhibit

peripheral somatosensory fibres, among other roles (Hartwig 1991). The studies show mixed

results, with Christian et al. (1988) and Sanders et al. (1990) reporting no changes to -endorphin

levels in symptomatic and asymptomatic populations following SM and compared to sham. In

contrast, Vernon et al. (1986) noted a small (8%) but significant increase in -endorphin levels

five minutes but not 10 or 30 minutes after cervical SM, compared to sham and control groups.

However there are concerns about the assay techniques used in each study, which bring into

question their results. The current studies on this topic are of insufficient quality to make any

conclusions regarding the effect of SM on serum -endorphin levels, so it remains unclear

whether the opioid system contributes to the hypoalgesia observed following SM. It may be that

HVLA SM does not stimulate the release of -endorphins, that the three studies to date have

failed to detect a change, or that serum -endorphins are an inappropriate measure. There are

similarly conflicting results from studies on other forms of manual therapy, reviewed by Bender

et al. (2007).

1.3.6.2. Substance P

Substance P is mainly involved in the transmission of slow nociceptive signals from peripheral

neurons to the dorsal horn (Snijdelaar et al. 2000; Todd 2010). Four studies have looked at

plasma substance P levels following SM. In a subset of participants studied by Brennan et al.

(1991), there were no significant changes to substance P levels in the group who received

thoracic SM group compared to sham SM. There was an increasing trend, but nine of the 30

26

participants had levels below the detection limit of the assay technique, so the remaining data

was underpowered (Brennan et al. 1991). Another subset in the same study compared SM to

baseline only, and found a statistically significant increase in substance P at 15 minutes post-SM

(Brennan et al. 1991). Brennan et al. (1992) also studied a subset of 30 participants, of whom

nine subjects’ blood samples could not be used due to technical difficulties, and found a

statistically significant increase in the levels of substance P 15 minutes after a thoracic SM,

though it is not stated if the data loss affected the statistical power of this finding. Teodorczyk-

Injeyan, Injeyan, and Ruegg (2006) compared thoracic SM to a ‘sham’ thoracic SM involving a

thrust but not eliciting a cavitation, and to venipuncture control. They investigated a variety of

biochemicals, measuring them 20 minutes and two hours after intervention. No significant

changes in substance P levels were noted in any group. Finally, Molina-Ortega et al. (2014)

demonstrated that serum substance P levels increased significantly immediately and two hours

after cervical SM but not thoracic SM and sham cervical SM, in an asymptomatic population. The

thoracic SM group did show a trend toward an increase, but with only ten participants per group,

there may have been insufficient power. Although generally accepted as having a pro-

nociceptive role, some have suggested substance P can also be involved in hypoalgesia (Molina-

Ortega et al. 2014). Given that Molina-Ortega et al. (2014) found a positive correlation between

substance P levels and PPT, this may be plausible. The significance of this is, however, uncertain,

and given that the four studies above show conflicting results it is perhaps unlikely that

substance P plays a significant role in post-SM hypoalgesia.

1.3.6.3. Cortisol

Salivary and serum cortisol levels have been investigated as a marker of stress responses to SM

in both symptomatic and asymptomatic populations. Four studies failed to find any significant

changes to cortisol levels immediately or at up to 5 weeks post-intervention (Christian et al.

1988; Padayachy et al. 2010; Tuchin 1998; Whelan et al. 2002). One study found cortisol levels

were significantly increased immediately but not 30 minutes after cervical HVLA SM in

27

asymptomatic participants compared to thoracic HVLA SM and control (Plaza-Manzano et al.

2014). It is conceivable that anxiety in anticipation of receiving SM, especially in naïve

participants, may affect cortisol levels, which could explain the short-lived change in cortisol

found in one study. Cortisol release is primarily stimulated by adrenocorticotropic hormone

(ACTH) via the hypothalamic-pituitary-adrenal axis (Tsigos and Chrousos 2002). In agreement

with the apparent lack of changes to cortisol following SM, Christian et al. (1988) also observed

no overall changes to the levels of ACTH following SM in the useable data they collected (almost

half of subjects had ACTH levels below the minimum detection level of the assay). It appears

unlikely that cortisol is involved in SM-induced hypoalgesia.

1.3.6.4. Other Biochemicals

In the study by Plaza-Manzano et al. (2014) serum levels of neurotensin, oxytocin, and orexin A

were observed following cervical or thoracic HVLA SM in asymptomatic subjects. Levels of

neurotensin and oxytocin were significantly increased in participants immediately after SM

compared to controls, but this did not persist at two hours post-intervention. Orexin A levels

remained unchanged. Each of the hormones investigated are known to have an analgesic role

in the body. Neurotensin’s analgesic function is independent of the opioid system, but can also

cause hyperalgesia in lower concentrations (St-Gelais, Jomphe, and Trudeau 2006). Oxytocin-

induced analgesia may involve direct stimulation of GABAergic spinal interneurons to inhibit Aδ-

and C-fibres, or indirectly through the endogenous opioid system (Millan 2002; Rash, Aguirre-

Camacho, and Campbell 2014). It is also plausible that the mood-enhancing and stress-reducing

effects of oxytocin contribute to its analgesic effect (Rash, Aguirre-Camacho, and Campbell

2014). Orexin A has a non-opioid analgesic mechanism and also potentially interplays with the

opioid system (Chiou et al. 2010). Nitric oxide is another chemical that is involved in nociception,

investigated by Molina-Ortega et al. (2014). Serum nitric oxide levels did not change following

either cervical SM, thoracic SM, or sham.

28

1.3.7. Theories for Post-Manipulation Hypoalgesia

Several theories may help to explain post-SM hypoalgesia (Bialosky et al. 2009a; Potter,

McCarthy, and Oldham 2005):

1. Activation of descending inhibitory pain control mechanisms

2. Activation of the pain gate mechanism

3. Altered spinal cord dorsal horn excitability

4. The placebo effect and psychosocial factors

1.3.7.1. Descending Inhibitory Pain Control Theory

A prominent theory is that SM produces activation of descending pain inhibition pathways.

Preliminary evidence suggests this may be mediated by serotonergic and noradrenergic, but not

opioidergic or GABAergic, pathways.

The descending pain pathways are highly complex, may inhibit or facilitate nociceptive signals,

and involve a variety of neurotransmitters including opioids, GABA, serotonin, and

noradrenaline (Millan 2002). Of particular relevance is the periaqueductal gray (PAG), situated

within the mesencephalon of the brainstem. It has been demonstrated that specific activation

of the PAG (particularly the dorsal portion) can result in mechanical hypoalgesia, altered

sympathetic tone and motor facilitation (Bandler and Shipley 1994, Benarroch 2012). The PAG

is activated in response to direct nociceptive and non-nociceptive inputs from the spinal cord,

and from a variety of supraspinal inputs (Benarroch 2012). It has projections to two areas of the

brainstem known to play an important role in descending pain modulation, the rostral ventral

medulla and dorsolateral pons (Benarroch 2012). Neurons from these areas modulate

nociceptive signals from dorsal horn neurons using serotonin and noradrenaline respectively

(Benarroch 2012, Millan 2002). This is simplistically illustrated in Figure 1.3. Additionally,

autonomic regions in the spinal cord receive significant innervation from related serotonergic

and noradrenergic descending pathways (Millan 2002).

29

Skyba et al. (2003) found that serotonergic and

noradrenergic inhibitory pathways were at least

partly responsible for the hypoalgesia following

knee mobilisation in rats, but opioids and GABA

did not appear to be involved. It is, however,

unclear whether joint mobilisation under

anaesthesia, in rodents, induces similar

biochemical changes to SM and thus these

results cannot be extrapolated to SM. Similar

human studies are limited, with three finding

that opioids are not involved in generating the

hypoalgesia following elbow mobilisation

(Paungmali et al. 2004), or spinal manual

therapy (by Vicenzino et al. 2000 and Zusman et

al. 1989, cited in Paungmali et al. 2004).

Alongside the mechanical hypoalgesia, altered autonomic tone has been observed following SM

in various studies. Decreased blood pressure and altered heart rate variability (predominantly

increased parasympathetic activity) has been noted (Mangum, Partna, and Vavrek 2012, Shafiq,

McGregor, and Murphy 2014, Win et al. 2015). Decreased skin blood flow, decreased skin

temperature, and increased skin conductance, following mobilisation has also been

demonstrated (Chu et al. 2014).

Skyba et al. (2003) postulate that afferent mechanical stimulation from joint manipulation

stimulates the PAG, which in turn activates the descending serotonergic and noradrenergic

pathways to inhibit nociceptive stimuli at the dorsal horn and alter autonomic output. This could

theoretically cause the observed post-manipulation hypoalgesia.

Figure 1.3. Serotonergic and noradrenergic

descending pain control pathways.

30

There is also some animal-model evidence that SM may alter pain processing in the lateral

thalamus (Reed et al. 2014). Since the PAG and thalamus have direct connections and exhibit a

reciprocal relationship related to pain modulation (Wu et al. 2014), it is postulated that SM may

affect pain processing in the thalamus via the PAG (Reed et al. 2014).

PAG-mediated hypoalgesia has been noted to primarily inhibit dorsal horn neurons relaying C-

fibre stimuli but not Aδ-fibre stimuli (Benarroch 2012). As highlighted in section 1.3, PPT

activates both C-fibres and Aδ-fibres, and thus would be expected to change following activation

of the PAG, while PPS stimulates only Aδ-fibres and thus would not be expected to change. It

has also been shown that SM elicits a reduction in TSS (see section 1.3.3), which is again

mediated by C-fibres, though thermal pain thresholds, mediated by Aδ-fibres, do not change.

We must also consider other biochemical research (see section 1.3.6). There is conflicting

evidence regarding serum β-endorphin (an opioid) levels following SM, though neurotensin and

oxytocin serum levels may increase. The release of oxytocin in the brainstem is modulated by

serotonergic and noradrenergic pathways, though its hypoalgesic effect is dependent upon

GABA and opioids in the dorsal horn (Millan 2002). Neurotensin, with its dual non-opioid hyper-

and hypo-algesic roles, is not well understood though is known to interplay with the

serotonergic system (Millan 2002; St-Gelais, Jomphe, and Trudeau 2006).

At present, early evidence from animal models and human studies, as well as basic science

research, fail to refute, and even support, the proposed serotonergic and noradrenergic

descending inhibitory pain control theory for post-SM hypoalgesia. More human studies to

determine if this is actually the case would be highly valuable and it is a promising direction for

future research.

31

1.3.7.2. Pain Gate Theory

The pain gate mechanism proposes that the transmission of nociceptive afferent impulses via

the dorsal horn can be inhibited by stimulating large-diameter fibres carrying non-nociceptive

afferent signals (muscle spindles, joint and cutaneous mechanoreceptors), essentially closing

the ‘gate’ and preventing nociceptive stimuli from reaching the brain (Melzack and Wall 1965).

Though details of the theory have altered over time with new research, this basic tenet is still

largely valid (Mendell 2014). It has been proposed that SM may activate the pain gate by

stimulating non-nociceptive receptors through muscle and/or facet joint stretch to generate

hypoalgesia (Potter, McCarthy, and Oldham 2005). No experimental research was identified to

support or refute this theory, though it is known (as discussed in section 1.3.4) that SM does

stimulate large-fibre mechanical afferent fibres that would be expected to activate the pain gain

mechanism. The pain gate is only a temporary mechanism to decrease transmission of

nociceptive signals while a concurrent non-nociceptive signal is being applied, so this is unlikely

to explain hypoalgesia that lasts beyond the actual treatment.

1.3.7.3. Altered Spinal Cord Dorsal Horn Excitability

Alteration of the excitability of neurons in the dorsal horn of the spinal cord (responsible for the

transmission of sensory information) in response to mechanical input has also been proposed

as a mechanism to explain post-SM hypoalgesia (Bialosky et al. 2009a). This primarily relates to

the findings of reduced TSS following SM (see section 1.3.3), which is considered to represent

reduced excitability of dorsal horn neurons (Anderson et al. 2013). This altered excitability could

theoretically affect transmission of nociceptive signals to the central nervous system and thus

mediate decreased pain sensitivity (Bishop, Beneciuk, and George 2011).

32

1.3.7.4. Placebo and Psychosocial Factors

The placebo effect is well known to occur with many interventions, and it is suggested by Potter,

McCarthy, and Oldham (2005) that SM is particularly susceptible to producing it. Maigne and

Vautravers (2003) discussed why:

A feeling that the vertebra has been returned to its normal position, a perception that

the cracking sound indicates effectiveness, and the manual contact preceding the

manipulation all contribute to the placebo effect. ... Finally, patients may perceive the

explanations supplied by SMT [spinal manipulative therapy] practitioners as more

satisfactory than those given by physicians [44].

Given that pain is a highly subjective experience, it is highly plausible that the placebo effect

may account for at least some of the hypoalgesia observed following SM. In addition,

expectation and other psychosocial factors such as fear can be involved (Bialosky et al. 2009a).

The current sham-controlled studies agree in finding greater hypoalgesia following SM than

sham (see section 1.3.1.3), which is encouraging for a real effect. It is however known to be

difficult to truly blind participants to manual therapies (Kawchuk, Haugen, and Fritz 2009).

1.4. State of the Literature

At present, there are significant gaps in our understanding of hypoalgesia following SM. We can

say with confidence that cervical SM leads to at least short term hypoalgesia. It appears that this

hypoalgesia is both local and remote, most likely only in locations with a direct neurological

connection to the site receiving SM. Thoracic SM may also produce hypoalgesia, while lumbar

SM seems not to alter local or remote pain sensitivity based on weaker evidence. The reason for

the conflicting findings between the cervical and lumbar spine remains unexplored. In addition,

research into the duration of hypoalgesia (particularly beyond 10 minutes), asymmetry, a dose-

response relationship, and differences between various populations (e.g. chronic pain vs.

33

asymptomatic) are scarce and no conclusions can be made in these areas. All of this research is

based upon PPT, and PPS remains unstudied in relation to SM. SM probably reduces TSS, and

maybe reduces chemical and electrical pain sensitivity as well.

Multiple theories for this hypoalgesia exist, and the explanation is likely complex and a

combination of factors (Bialosky et al. 2009a). Descending inhibitory pain control mechanisms,

pain gait mechanisms, altered spinal cord dorsal horn excitability, placebo and psychosocial

factors may each be involved.

The present study aims to add to the limited body of research looking at the effect of lumbar

SM on local and remote hypoalgesia to help clarify whether any effect occurs, if any effect is

local or remote, and if remote, whether it is segmental or non-segmental in nature. This study

also sets out to explore some of the current gaps by following pain sensitivity for 30 minutes,

longer than the majority of studies, and investigating any asymmetry in hypoalgesia.

As such, the research questions under investigation are:

1) Does lumbar SM affect pain sensitivity (deep and superficial) at local and remote

locations?

2) Do changes last for at least 30 minutes?

3) Are any changes related to the side of manipulation (i.e. bilateral symmetric or

asymmetric)?

2. Methods

This study followed a single-blind randomised parallel trial design. It was registered with the

Australian New Zealand Clinical Trials Registry (registration number: ACTRN12614000682640,

available at www.anzctr.org.au/ACTRN12614000682640.aspx).

34

2.1. Power Calculation

G*Power 3.1 software (University of Düsseldorf, Germany) was used for a power analysis. A

sample of 34 participants and an estimated effect size of 0.4 provides 80% power to detect a

significant difference for within and between group changes in PPT and PPS. The sample size

was limited by the time available to complete the study, thus the large effect size of 0.4 satisfied

80% power and maintained an achievable sample size.

2.2. Participant Recruitment

Participants were recruited from the student population at Murdoch University through oral

announcements during classes, flyers around the Murdoch University Campus, and the general

public via personal contacts of the first investigator.

Participants were required to be between 18 and 45 years of age, and were precluded from the

study if any of the following exclusion criteria were met:

1. Current chronic pain condition

2. Current acute or sub-acute LBP

3. Existing contraindication/s to lumbar spinal manipulation (WHO 2005), which included:

Lumbar spine fracture/dislocation, lumbar instability, lumbar intervertebral disc

or other injury, or lumbar spine surgery.

Spinal infection, spine or spinal cord tumour, rheumatologic disease,

neurological disease, lower limb neurologic symptoms, bleeding disorder, anti-

coagulant therapy, recent onset severe headache, recent infection, generalised

hypermobility, or low bone density.

4. Qualified chiropractor or student in 4th or 5th year of chiropractic university degree

5. Taken pain-relieving medication in the previous 24 hours

6. Had alcohol within the previous 12 hours

35

Upon commencement of data collection, chiropractic students at all stages of study were

excluded from participation in the interest of reducing expectancy bias among participants.

Significant difficulty in recruiting participants led to a change in the exclusion criteria, allowing

chiropractic students in their 1st, 2nd and 3rd year of study to participate. These students had yet

to receive formal lectures on the neurological effects of spinal manipulation, and thus presumed

to be less likely to introduce expectancy bias.

2.3. Randomisation

Participants were randomly assigned to group 1 or 2. Group 1 received the intervention on the

right, while group 2 received the intervention on the left. A randomisation list consisting of equal

numbers of 1s and 2s was created using the GraphPad random number generator (available at

www.graphpad.com/quickcalcs/randomN1/), and placed in sequentially numbered, opaque,

sealed envelopes by the second investigator (providing the intervention). The second

investigator used these envelopes to allocate participants to their groups immediately prior to

the intervention. Due to the nature of the intervention, participants were unable to be blinded.

2.4. Procedure

Data was collected in a designated research room at the Murdoch University campus. The

participant completed a relevant medical history form (Appendix A) to ensure eligibility, and was

then provided with an Information Letter to read (Appendix B) followed by informed consent

(Appendix C). The participants’ dominant hand was also recorded. The participant was

requested to wear appropriate clothing on the day, to allow access to the areas under

investigation. If clothing prevented access to the skin at these sites, the participant was asked

to don a clean clinical examination gown for the duration of the study.

The following points were then marked bilaterally on the participant’s skin with a non-

permanent marker by the first investigator (Figure 2.1):

36

2cm lateral and inferior to the root

of the spine of the scapula, over the

infraspinatus muscle,

2cm lateral to the L5 spinous

process, over the lumbar

paraspinal muscles,

Half way down the medial head of

the gastrocnemius muscle, and

The frontal eminence of the frontal

bone.

The scapular site was chosen as an easily

accessible remote location that has no neurological connection with the region of the spine

receiving manipulation. The lumbar site is local, being directly adjacent to the site of

manipulation. The gastrocnemius site was chosen as it is innervated by L5/S1, thus is

segmentally related to the site of manipulation. The frontal eminence site was chosen as it is

remote and lies within the cranial nerve distribution. These were chosen to allow us to

determine whether any effects of lumbar spinal manipulation were purely local, segmental, or

centrally driven.

The PPT and PPS measures were taken by the first investigator, at the above locations. The

procedure for measuring PPT and PPS was explained to the participant, and baseline

measurements taken at the eight sites. The intervention was then applied to the participant by

the second investigator, while the first investigator left the room (thus blinded to the side of

intervention). PPT and PPS were then measured by the first investigator at each site immediately

after the intervention, and at 10 minutes, 20 minutes and 30 minutes post-intervention. The

participant was then free to leave.

Figure 2.1. Testing sites.

37

2.5. Pressure Pain Threshold

PPT was measured using a Wagner FDIX pressure

algometer with a 1cm2 rubber probe. This was

standardised and calibrated against a Kistler force

plate prior to taking outcome measures. The

participant was instructed on the procedure, and

asked to say “Yes” when the sensation of pressure

from the algometer first changed to pain. The

algometer was placed perpendicular to the skin and

increasing pressure applied at a rate of 500g/s until the participant said “Yes”, at which point

the investigator removed the algometer and the maximum was pressure recorded (Figure 2.2).

This technique was described and validated by Fischer (1987). Two practice measurements on

the back of the hand were performed first, to ensure the participant understood the procedure.

Actual measurements were performed three times at each site, following a circuit to allow

sufficient rest time between measures at each site. The participant lay prone, having the first

measure at the gastrocnemius, lumbar and infraspinatus sites on each side (left then right) taken

in succession. The participant was then asked to lay supine to take the first forehead

measurements. This was repeated twice more to achieve a total of three measures per site. This

method was validated by Bisset, Evans, and Tuttle (2015). The average of the second and third

measures was used for analysis, found to be reliable by Lacourt, Houtveen, and van Doornen

(2012). The cut-off point was set at 10kg/cm2 for the forehead and infraspinatus sites (Lacourt,

Houtveen, and van Doornen 2012), and at 12.5kg/cm2 for the lumbar and gastrocnemius sites

as this was the upper measurement limit of the algometer. If the pressure reached this value

without the participant saying “Yes”, the cut off value was taken as the value for that

measurement and no further pressure applied.

Figure 2.2. Wagner algometer.

38

2.6. Pinprick Sensitivity

PPS was measured by determining

the intensity of a pinprick

sensation, using the Neuropen

(Owen Mumford 2014) with

Neurotips™ (Figure 2.3). This device

is designed to consistently exert 40g of force when the Neurotip™ is pressed into the skin (Owen

Mumford 2014), though no reliability studies exist. An 11-point Numerical Rating Scale (NRS)

was used where 0 = not sharp, and 10 = extremely sharp, as used previously in an experimental

trial (Vo and Drummond 2013). The Neurotip™ was placed perpendicular to the skin and pressed

in until the guiding markers on the Neuropen were aligned, maintained for one second and then

the Neurotip™ removed. The participant was asked to verbally report the severity of the

sharpness using the NRS. Two practice measurements on the muscle bulk at the base of the

thumb were performed first. Actual measurements were performed once at each site,

immediately following the completion of all PPT measures. A new Neurotip™ was used for each

participant, with used tips being discarded into a sealable sharps container.

2.7. Spinal Manipulation

HVLA SM was applied to the L5-S1 spinal segment. A technique commonly used by chiropractors,

referred to as the hypothenar mammillary push (Bergmann and Peterson 2011, 253-254), was

used (Figure 2.4). The second

investigator (with 15 years of

clinical and academic experience)

applied the SM with the participant

in the side-lying position, taking a

contact upon the L5 mamillary

process on the appropriate side of

Figure 2.3. Neuropen with semi-sharp tip.

Figure 2.4. Right-sided L5 spinal manipulation technique.

39

the participant, based on their randomisation. For example, if the participant was randomised

to group 1, they were asked to lie on their left-hand side and the SM was applied to the right

side of the lumbar spine. The success of the procedure was subjectively determined by the

investigator, and not based upon the occurrence of a cavitation which seems to be unimportant

(see section 1.2.3).

2.8. Data Analysis

The algometer used in this study was standardised against a standard Kistler force plate prior to

collecting data. Pearson’s coefficient of correlation (two-tailed) and the mean of the differences

was determined using SPSS version 23.

Pain sensitivity data was entered into and analysed using the statistical package SPSS Version

23. The data was checked for implausabilities and outliers, and five random samples were

examined for data entry errors. A repeated measures analysis of variance was conducted for

PPT and for PPS, at each location (calf, lumbar spine, scapula, and forehead). Each had factors

of Time (baseline, immediately after intervention, 10min, 20min and 30min), Side

(measurement taken on right or left side of the body), and Group (participants received either

right lumbar SM [R-SM] or left lumbar SM [L-SM]). Simple contrasts between baseline and each

subsequent time point were included in the analyses to investigate effects of the intervention

at each time point. Further interactions were investigated using paired t-tests. Mean PPT or PPS

values and standard deviations (SD) are reported for each significant interaction. Effect sizes are

reported in the form of partial Eta squared (ηP2), where ≥0.10, ≥0.25, and ≥0.50 are considered

to represent small, moderate and large effect sizes respectively (Richardson 2011).

40

3. Results

3.1. Algometer Standardisation

The Wagner FDIX algometer was standardised against a Kistler Force Plate prior to data

collection. The correlation was 0.99, which is significant at the p = 0.01 level (2-tailed). The line

of best fit had a slope of y = 0.11+0.97*x (Figure 3.1). There is however, a mean difference in the

readings between the two instruments of 0.30kg/cm2 (SD 0.10). It was determined that the

Wagner algometer was a reliable and valid instrument for the purposes of this study.

Kistler vs. Wagner pressure correlation

Kistler force plate measurement (kg/cm2)

0 1 2 3 4 5 6 7 8 9 10

Wa

gn

er

alg

om

ete

r m

ea

su

rem

en

t (k

g/c

m2)

1

2

3

4

5

6

7

8

9

10

Figure 3.1. Correlation between Wagner algometer and Kistler force plate pressure measurements.

3.2. Pain Sensitivity Results

In total, 34 participants (20 male) completed data collection and were included in analysis

(Figure 3.2), with an average age of 22.56 years (SD 3.99, range 18 - 36 years). Data was collected

between October 2014 and June 2015, and recruitment ended when 34 participants had

successfully completed data collection. Baseline characteristics of the participants are reported

in Table 3.1. No harms were reported during or after the follow-up period.

41

Figure 3.2. Flow diagram of trial, investigating right vs. left lumbar spinal manipulation for pressure

pain threshold and pinprick sensitivity.

Table 3.1. Baseline characteristics.

R-SM L-SM

Actual difference

(% difference)

Gender 8 female, 9 male 6 female, 11 male -

Age (mean age in years) 22.59 (SD 3.10) 22.53 (SD 4.81) 0.06 (0.27)

Dominant hand 11 right, 6 left 16 right, 1 left -

Calf PPT (kg/cm2) 5.10 (SD 2.23) 4.48 (SD 1.87) 0.62 (12.16)

Lumbar Spine PPT (kg/cm2) 7.12 (SD 2.88) 5.89 (SD 2.64) 1.23 (17.28)

Scapula PPT (kg/cm2) 5.05 (SD 1.89) 4.13 (SD 1.85) 0.92 (18.22)

Forehead PPT (kg/cm2) 2.83 (SD 0.96) 2.38 (SD 0.95) 0.45 (15.90)

Calf PPS (0-10 scale) 4.12 (SD 2.18) 5.12 (SD 2.36) 1.00 (19.53)

Lumbar Spine PPS (0-10 scale) 4.32 (SD 1.60) 5.26 (SD 2.14) 0.94 (17.87)

Scapula PPS (0-10 scale) 3.24 (SD 1.69) 4.53 (SD 2.01) 1.29 (28.48)

Forehead PPS (0-10 scale) 4.35 (SD 1.79) 5.26 (SD 2.35) 0.91 (17.30)

Abbreviations: SD = standard deviation, PPT = pressure pain threshold, PPS = pinprick sensitivity.

42

Two cells had missing data, the first due to an algometer error and the second due to a recording

error. These two missing values were Left Scapula PPT at Baseline for participant six, and Right

Lumbar PPT Immediately after Intervention for participant 19. For participants with complete

data, the second and third PPT measures at the specific location and time point were averaged

to arrive at a given cell’s value, with the first PPT measure remaining unused. Since the cells of

interest were missing the second and third, respectively, of their PPT measures, the data for

those cells were imputed by substituting just the remaining third or second measure

respectively, into the cell. This imputed value was decided to be most appropriate as t-tests

revealed that the means of the second and third PPT measures in each participant were very

similar (Table 3.2). The differences in the means between the first and second, and first and third

measures were non-significant in participant 6 (but with a greater mean difference than second

vs. third), and significantly different in participant 19. Thus it was concluded that imputing the

data in this conservative manner as described above was likely to give the closest estimate of

the true value.

Table 3.2. Comparison of first, second and third PPT measures in participants with missing data.

p-value (mean PPT difference in kg/cm2)

Participant 6

scapula

Participant 19

lumbar spine

First vs. second .172 (0.636) .013* (1.43)

Second vs. third .846 (-0.05) .729 (-0.18)

First vs. third .279 (0.30) .026* (1.26)

Abbreviations: PPT = pressure pain threshold, * = p ≤ .05.

The Shapiro-Wilk test for normality indicated numerous deviations from a normal distribution

(see Appendix D). The repeated measures ANOVA is generally considered to be fairly robust to

deviations from normality, unless the deviations are extreme or the sample size particularly low

(Norman and Streiner 2008). Visual inspection of the data’s histograms and Q-Q plots revealed

only mild to moderate deviations from a normal distribution. Thus it was concluded that the

repeated measures ANOVA was an appropriate test to use for this data.

43

3.2.1. Calf Pressure Pain Threshold

There was a significant main effect for Time (p = .034 [with Greenhouse-Geisser correction])

with a weak effect size (ηP2 = .09). Post-hoc tests revealed a trend that approached statistical

significance between calf PPT at baseline and 10min, and significant differences between

baseline and 20min, and baseline and 30min, each with weak effect sizes. There was no

significant difference between baseline and immediately after SM. These data indicate an

increase in calf PPT over time, which was significant at 20min and 30min, of 9.6% and 9.0%

respectively (Table 3.3 and Figure 3.3).

Table 3.3. Mean calf PPT at baseline, immediately after intervention, and at 10, 20, and 30 minutes.

Mean calf PPT, kg/cm2

Actual difference

compared to Baseline in

kg/cm2 (% difference)

p-value for difference

compared to Baseline

Baseline 4.79 (SD 2.05) - -

Immediate 5.05 (SD 2.23) 0.26 (5.4%) .111 (ηP2 .08)

10min 5.14 (SD 2.18) 0.35 (7.3%) .053 (ηP2 .11)

20min 5.25 (SD 2.17) 0.46 (9.6%) .017* (ηP2 .17)

30min 5.22 (SD 2.00) 0.43 (9.0%) .027* (ηP2 .14)

Abbreviations: PPT = pressure pain threshold, SD = standard deviation, ηP2 = effect size, * = p ≤ .05.

Calf, lumbar spine, scapula and forehead PPT over time

Time

Baseline Immediate 10min 20min 30min

PP

T (

kg

/cm

2)

0

1

2

3

4

5

6

7

8

* * *

* *

Lumbar

spine

Calf

Scapula

Forehead

Figure 3.3. Mean calf, lumbar spine, scapula and forehead PPT at baseline, immediately after

intervention, and at 10, 20, and 30 minutes. Abbreviations: PPT = pressure pain threshold, * = p ≤ .05.

44

There was a significant main effect for Side (p = .001) with a moderate effect size (ηP2 = .32). Calf

PPT had a mean of 5.37 kg/cm2 (SD 2.17) on the right, and 4.81 kg/cm2 (SD 2.02) on the left.

These data indicate that the right calf had a significantly higher PPT than the left calf, with a

difference of 0.56 kg/cm2.

There was no significant overall effect for Time by Side by Group (p = .201, ηP2 = .05). However,

within-subject contrasts revealed a significant difference with weak effect size between baseline

and 10min, and a trend toward significance between baseline and 20min. There were no

differences between baseline and immediately after SM, or baseline and 30min. The difference

between the right and left calf PPT measures appears to increase by 0.45 kg/cm2 after R-SM, but

decrease by 0.19 kg/cm2 after L-SM, when comparing baseline to 10min (Table 3.4 and Figure

3.4).

Table 3.4. Mean calf PPT on the right and left sides in each group, at baseline, immediately after

intervention, and at 10, 20, and 30 minutes.

Mean calf PPT, kg/cm2 p-value for

difference

compared to

Baseline R-SM group L-SM group

Baseline Right 5.30 (SD 2.49) Right 4.79 (SD 1.77) -

Left 4.90 (SD 2.17) Left 4.17 (SD 2.06)

Immediate Right 5.65 (SD 2.29) Right 4.95 (SD 2.60) .207 (ηP

2 .05) Left 5.07 (SD 1.82) Left 4.55 (SD 2.39)

10min Right 5.76 (SD 2.56) Right 5.16 (SD 2.19) .032* (ηP

2 .14) Left 4.91 (SD 2.01) Left 4.73 (SD 2.22)

20min Right 5.78 (SD 1.99) Right 5.21 (SD 2.51) .061 (ηP

2 .11) Left 5.06 (SD 1.92) Left 4.93 (SD 2.52)


2 .06) Left 4.90 (SD 1.73) Left 4.87 (SD 2.24)

Abbreviations: PPT = pressure pain threshold, R-SM = right-sided spinal manipulation, L-SM = left-sided

spinal manipulation, SD = standard deviation, ηP2 = effect size, * = p ≤ .05.

45

Calf PPT Time by Side by Group

Time

Baseline Immediate 10 min 20 min 30 min

PP

T (

kg

/cm

2)

0

2

3

4

5

6

7

R-SM Right Calf

R-SM Left Calf

L-SM Right Calf

L-SM Left Calf

Figure 3.4. Mean calf PPT on the right and left sides in each group, at baseline, immediately after

intervention, and at 10, 20, and 30 minutes. Abbreviations: PPT = pressure pain threshold, R-SM = right-

sided spinal manipulation, L-SM = left-sided spinal manipulation.

There were no significant effects for Group (p = .550, ηP2 = .01), Time by Group (p = .520, ηP

2 =

.03), Side by Group (p = .459, ηP2 = .02), or Time by Side (p = .699, ηP

2 = .02) for calf PPT.

3.2.2. Lumbar Spine Pressure Pain Threshold


with a weak effect size (ηP2 = .15). Post-hoc tests revealed significant differences with weak

effect sizes between lumbar PPT at baseline and 10min, baseline and 20min, and baseline and

30min, but not between baseline and immediately after SM. These data indicate a significant

increase in lumbar spine PPT from baseline to 10min, 20min and 30min of 7.2%, 9.2% and 11.8%


46

Table 3.5. Mean lumbar spine PPT at baseline, immediately after intervention, and at 10, 20, and 30

minutes.

Mean lumbar spine

PPT, kg/cm2

Actual difference compared to Baseline in


p-value for difference compared to Baseline

Baseline 6.50 (SD 2.79) - -

Immediate 6.74 (SD 2.72) 0.24 (3.7%) .247 (ηP2 .04)

10min 6.97 (SD 2.53) 0.47 (7.2%) .033* (ηP2 .13)

20min 7.10 (SD 2.66) 0.6 (9.2%) .011* (ηP2 .19)

30min 7.27 (SD 2.61) 0.77 (11.8%) .007* (ηP2 .21)


There was a significant main effect for Side (p = .006) with a weak effect size (ηP2 = .21). Lumbar

PPT had a mean of 7.11 kg/cm2 (SD 2.71) on the right, and 6.72 kg/cm2 (SD 2.51) on the left.

These data indicate that the right lumbar spine had a significantly higher PPT than the left lumbar

spine, with a difference of 0.39 kg/cm2.

There was an effect approaching significance for Side by Group (p = .057) with a weak effect size

(ηP2 = .11). The difference between right and left lumbar PPT was greater after R-SM than after

L-SM, but this did not reach significance (Table 3.6).

Table 3.6. Mean lumbar spine PPT on right and left sides in each group.

Mean lumbar spine PPT, kg/cm2 Actual difference

between sides in

kg/cm2 (% difference) Right side Left side

R-SM group 7.85 (SD 2.59) 7.19 (SD 2.43) 0.66 (8.4%)

L-SM group 6.38 (SD 2.70) 6.25 (SD 2.57) 0.13 (2.0%)


spinal manipulation, SD = standard deviation.

There was no main effect for Group (p = .178, ηP2 = .06), and no significant effects for Time by

Group (p = .975, ηP2 = .00), Time by Side (p = .340, ηP

2 = .03), or Time by Side by Group (p = .245,

ηP2 = .04) for lumbar spine PPT.

47

3.2.3. Scapula Pressure Pain Threshold

There were no main effects for Time (p = .705 [with Greenhouse-Geisser correction], ηP2 =

.01)(Table 3.7 and Figure 3.3), Side (p = .865, ηP2 = .00), or Group (p = .098, ηP

2 = .08) for scapula

PPT.

Table 3.7. Mean scapula PPT at baseline, immediately after intervention, and at 10, 20, and 30

minutes.

Mean scapula PPT,

kg/cm2

Actual difference compared to Baseline in



Baseline 4.59 (SD 1.90) - -

Immediate 4.58 (SD 2.03) -0.01 (0.2%) .881 (ηP2 .00)

10min 4.70 (SD 2.05) 0.11 (2.4%) .450 (ηP2 .02)

20min 4.71 (SD 1.95) 0.12 (2.6%) .439 (ηP2 .02)

30min 4.68 (SD 1.71) 0.09 (2.0%) .581 (ηP2 .01)

Abbreviations: PPT = pressure pain threshold, SD = standard deviation, ηP2 = effect size.

There was no overall significant effect for Time by Side (p = .271 [with Greenhouse-Geisser

correction], ηP2 = .04). Within-subject contrasts revealed a significant difference with weak effect

size between baseline and immediately after SM, but not between baseline and 10min, baseline

and 20min, or baseline and 30min. These data indicate that there was a significant difference

where at baseline, right scapula PPT was higher than the left, but immediately following the SM,

right scapula PPT was lower than the left. The actual differences, however, were small (Table

3.8).

Table 3.8. Mean scapula PPT on the right and left sides at baseline, immediately after intervention,

and at 10, 20, and 30 minutes.

Mean scapula PPT, kg/cm2 Actual difference

between sides in


p-value for diff-

erence compared

to Baseline Right side Left side

Baseline 4.65 (SD 2.03) 4.54 (SD 1.92) 0.11 (2.4%) -

Immediate 4.50 (SD 2.14) 4.65 (SD 2.07) -0.15 (3.3%) .032* (ηP2 .14)

10min 4.75 (SD 2.24) 4.64 (SD 1.99) 0.11 (2.3%) .992 (ηP2 .00)

20min 4.75 (SD 2.10) 4.66 (SD 1.94) 0.09 (1.9%) .797 (ηP2 .00)

30min 4.66 (SD 1.76) 4.69 (SD 1.81) -0.03 (0.6%) .403 (ηP2 .02)


48

The Time by Side by Group interaction was nearing significance (p = .064, ηP2 = .07). Contrasts

revealed a significant difference between baseline and 20min with a weak effect size, but not

between baseline and immediately after SM, baseline and 10min, or baseline and 30min. After

R-SM, the difference between the right and left scapula PPT measures appears to increase from

baseline to 20min, with the right remaining higher than the left. After L-SM, scapula PPT is

almost identical at baseline, with the left PPT becoming higher than the right at 20min (Table

3.9 and Figure 3.5).

Table 3.9. Mean scapula PPT on the right and left sides in each group, at baseline, immediately after

intervention, and at 10, 20, and 30 minutes.

Mean scapula PPT, kg/cm2 p-value for

difference

compared to



Left 4.94 (SD 1.83) Left 4.14 (SD 1.97)

Immediate Right 5.27 (SD 2.12) Right 3.74 (SD 1.94) .145 (ηP

2 .07) Left 5.12 (SD 1.69) Left 4.18 (SD 2.35)


2 .00) Left 5.25 (SD 2.03) Left 4.03 (SD 1.82)

20min Right 5.36 (SD 1.98) Right 4.13 (SD 2.09) .030* (ηP

2 .14) Left 4.88 (SD 1.63) Left 4.45 (SD 2.24)


2 .01) Left 5.18 (SD 1.77) Left 4.21 (SD 1.77)



49

Scapula PPT Time by Side by Group

Time


PP

T (

kg

/cm

2)

0

2

3

4

5

6

R-SM Right Scapula

R-SM Left Scapula

L-SM Right Scapula

L-SM Left Scapula

Figure 3.5. Mean scapula PPT on the right and left sides in each group, at baseline, immediately after



There were no significant effects for Time by Group (p = .255, ηP2 = .04) or Side by Group (p =

.235, ηP2 = .04) for scapula PPT.

3.2.4. Forehead Pressure Pain Threshold

There were no main effects for Time (p = .668 [with Greenhouse-Geisser correction], ηP2 =

.01)(Table 3.10 and Figure 3.3), Side (p = .641, ηP2 = .01), or Group (p = .256, ηP

2 = .04) for

forehead PPT.

Table 3.10. Mean forehead PPT at baseline, immediately after intervention, and at 10, 20, and 30

minutes.

Mean forehead PPT,

kg/cm2

Actual difference compared to Baseline, kg/cm2 (% difference)


Baseline 2.61 (SD 0.97) - -

Immediate 2.67 (SD 1.06) 0.06 (2.3%) .399 (ηP2 .02)

10min 2.67 (SD 1.08) 0.06 (2.3%) .446 (ηP2 .02)

20min 2.66 (SD 0.99) 0.05 (1.9%) .582 (ηP2 .01)

30min 2.69 (SD 1.03) 0.08 (3.1%) .344 (ηP2 .03)

Abbreviations: PPT = pressure pain threshold, SD = standard deviation, ηP2 = effect size.

50

The interaction Time by Side was nearing significance (p = .059, ηP2 = .07). Contrasts revealed a

significant difference with weak effect size between baseline and 20min, but no significant

differences between baseline and immediately after SM, baseline and 10min, or baseline and

30min. The data indicate that at baseline, forehead PPT on the right was higher than the left,

however at 20min, the left was higher than the right. The differences were very small (Table

3.11).

Table 3.11. Mean forehead PPT on the right and left sides at baseline, immediately after intervention,


Mean forehead PPT, kg/cm2 Actual difference

between sides in


p-value for diff-

erence compared


Baseline 2.64 (SD 1.04) 2.57 (SD 0.93) 0.07 (2.7%) -

Immediate 2.67 (SD 1.15) 2.67 (SD 1.00) 0.00 (0.0%) .214 (ηP2 .05)

10min 2.71 (SD 1.18) 2.64 (SD 1.03) 0.07 (2.6%) .947 (ηP2 .00)

20min 2.63 (SD 1.04) 2.69 (SD 0.98) -0.06 (2.3%) .014* (ηP2 .18)

30min 2.72 (SD 1.10) 2.66 (SD 0.98) 0.06 (2.2%) .721 (ηP2 .00)


There was no significant overall Time by Side by Group interaction (p = .180, ηP2 = .05), but

contrasts revealed a significant difference with weak effect size between baseline and

immediately after SM. There were no significant differences between baseline and 10min,

baseline and 20min, or baseline and 30min. The difference between the right and left forehead

PPT measures appears to decrease after R-SM, but increase after L-SM, when comparing

baseline to immediately after SM (Table 3.12 and Figure 3.6). However, the differences were

quite small, between 0.05 - 0.11kg/cm2.

51

Table 3.12. Mean forehead PPT on the right and left sides in each group, at baseline, immediately

after intervention, and at 10, 20, and 30 minutes.

Mean forehead PPT, kg/cm2 p-value for

difference

compared to



Left 2.75 (SD 0.90) Left 2.39 (SD 0.96)

Immediate Right 2.82 (SD 0.97) Right 2.53 (SD 1.32) .017* (ηP

2 .17) Left 2.86 (SD 0.87) Left 2.47 (SD 1.10)


2 .03) Left 2.82 (SD 1.01) Left 2.46 (SD 1.05)


2 .05) Left 2.88 (SD 0.88) Left 2.50 (SD 1.05)


2 .02) Left 2.84 (SD 0.82) Left 2.49 (SD 1.12)



There were no significant effects for Time by Group (p = .953, ηP2 = .01) or Side by Group (p =

.671, ηP2 = .01) for forehead PPT.

Forehead PPT Time by Side by Group

Time


PP

T (

kg

/cm

2)

0

1

2

3

4

R-SM Right Forehead

R-SM Left Forehead

L-SM Right Forehead

L-SM Left Forehead Figure 3.6. Mean forehead PPT on the right and left sides in each group, at baseline, immediately after



52

3.2.5. Calf Pinprick Sensitivity

There was a significant main effect for Time (p = .008) with a weak effect size (ηP2 = .10). Within-

subject contrasts revealed a significant difference between baseline and 20min, and baseline

and 30min, each with a weak effect size. There were no significant differences between baseline

and immediately after SM, or baseline and 10min. These data indicate that calf PPS scores

decreased over time, which was significant when comparing baseline to 20min and 30min, with

11.5% and 13.6% change respectively (Table 3.13 and Figure 3.7).

Table 3.13. Mean calf PPS at baseline, immediately after intervention, and at 10, 20, and 30 minutes.

Mean calf PPS, 0-10

scale

Actual difference compared to Baseline (%

difference)


Baseline 4.62 (SD 2.29) - -

Immediate 4.60 (SD 2.07) 0.02 (0.4%) .943 (ηP2 .00)

10min 4.47 (SD 2.41) 0.15 (3.2%) .514 (ηP2 .01)

20min 4.09 (SD 2.22) 0.53 (11.5%) .039* (ηP2 .13)

30min 3.99 (SD 2.21) 0.63 (13.6%) .021* (ηP2 .16)

Calf PPS over time

Time


PP

S (

0-1

0 s

ca

le)

0

1

2

3

4

5

6

7

8

* *

Figure 3.7. Mean calf PPS at baseline, immediately after intervention, and at 10, 20, and 30 minutes

with standard deviation bars. Abbreviations: PPS = pinprick sensitivity, * = p ≤ .05.

Abbreviations: PPS = pinprick sensitivity, SD = standard deviation, ηP2 = effect size, * = p ≤ .05.

53

There was a significant main effect for Side (p = .049) with a weak effect size (ηP2 .12). The mean

right calf PPS (4.45 [SD 2.08]) was significantly higher than the mean left calf PPS (4.25 [SD 2.15]),

with a mean difference of 0.2.

There was no overall interaction for Time by Side (p = .291, ηP2 = .04). However, contrasts

revealed a significant difference between baseline and 20min with weak effect size. There were

no significant differences between baseline and immediately after SM, baseline and 10min, or

baseline and 30min. These data indicate that there was a significant difference, where the

difference between right and left calf PPS at baseline was significantly smaller than the

difference at 20min (Table 3.14).

There was no significant main effect for Group (p = .218, ηP2 = .05). There were no significant

interactions for Time by Group (p = .944, ηP2 = .01), Side by Group (p = .287, ηP

2 = .04), or Time

by Side by Group (p = .506, ηP2 = .03).

Table 3.14. Mean calf PPS on the right and left sides at baseline, immediately after intervention, and

at 10, 20, and 30 minutes.

Mean calf PPS, 0-10 scale Actual difference

between sides (%

difference)

p-value for diff-

erence compared


Baseline 4.68 (SD 2.16) 4.56 (SD 2.54) 0.12 (2.6%) -


10min 4.47 (SD 2.55) 4.47 (SD 2.40) 0.00 (0.0%) .679 (ηP2 .01)

20min 4.38 (SD 2.40) 3.79 (SD 2.14) 0.59 (13.5%) .042* (ηP2 .12)

30min 4.12 (SD 2.13) 3.85 (SD 2.52) 0.27 (6.6%) .563 (ηP2 .01)


3.2.6. Lumbar Spine Pinprick Sensitivity

There was a significant main effect for Time (p = .000), with a weak effect size (ηP2 = .21). Post-

hoc testing revealed a significant difference between all levels, baseline and immediately after

SM, 10min, 20min, and 30min, each with weak to moderate effect sizes. These data indicate

54

that lumbar spine PPS decreased over time from baseline to each time point by 13.4%, 18%,

17.1% and 22.5% at 10min, 20min and 30min respectively (Table 3.15 and Figure 3.8).

There were no main effects for Side (p = .910, ηP2 = .00) or Group (p = .255, ηP

2 = .04). There were

no significant interactions for Time by Group (p = .575, ηP2 = .02), Side by Group (p = .279 , ηP

2 =

.04), Time by Side (p = .600, ηP2 = .02), or Time by Side by Group (p = .753, ηP

2 = .02).

Table 3.15. Mean lumbar spine PPS at baseline, immediately after intervention, and at 10, 20, and 30

minutes.

Mean lumbar spine

PPS, 0-10 scale

Actual difference compared to Baseline (%

difference)


Baseline 4.79 (SD 1.92) - -

Immediate 4.15 (SD 2.11) 0.64 (13.4%) .003* (ηP2 .24)

10min 3.93 (SD 2.35) 0.86 (18.0%) .001* (ηP2 .30)

20min 3.97 (SD 1.99) 0.82 (17.1%) .001* (ηP2 .29)

30min 3.71 (SD 2.16) 1.08 (22.5%) .000* (ηP2 .42)


Lumbar PPS over time

Time


PP

S (

0-1

0 s

ca

le)

0

1

2

3

4

5

6

7

8

* **

*

Figure 3.8. Mean lumbar spine PPS at baseline, immediately after intervention, and at 10, 20, and 30

minutes with standard deviation bars. Abbreviations: PPS = pinprick sensitivity, * = p ≤ .05.

55

3.2.7. Scapula Pinprick Sensitivity

There was no significant main effect for time (p = .127, ηP2 = .054). Post-hoc testing revealed a

significant difference between baseline and 10min, and baseline and 20min with weak effect

sizes, but not between baseline and immediately after SM, or baseline and 30min. The data

indicate that scapula PPS decreased from baseline to 10min and 20min by 12.4% and 9.8%


Table 3.16. Mean scapula PPS at baseline, immediately after intervention, and at 10, 20, and 30

minutes.

Mean scapula PPS, 0-

10 scale

Actual difference compared to Baseline

(% difference)


Baseline 3.88 (SD 1.94) - -

Immediate 3.62 (SD 2.07) 0.26 (6.7%) .278 (ηP2 .04)

10min 3.40 (SD 1.91) 0.48 (12.4%) .025* (ηP2 .15)

20min 3.50 (SD 2.07) 0.38 (9.8%) .035* (ηP2 .13)

30min 3.54 (SD 1.95) 0.34 (8.8%) .111 (ηP2 .08)


Scapula PPS over time

Time


PP

S (

0-1

0 s

ca

le)

0

1

2

3

4

5

6

7

8

* *

Figure 3.9. Mean scapula PPS at baseline, immediately after intervention, and at 10, 20, and 30


There was a significant main effect for Group with a weak effect size (p = .041, ηP2 = .12), where

the R-SM group had a mean scapula PPS of 2.94 (SD 1.38), and the L-SM group had a mean of

56

4.24 (SD 2.09). This is likely explained by baseline differences in scapula PPS, which were

substantially lower after R-SM than L-SM (Table 3.1).

There was a significant interaction for Side by Group (p = .028) with a weak effect size (ηP2 = .14).

The data indicate that there was a significant difference where after R-SM, right scapula PPS was

lower than the left, but after L-SM, right scapula PPS was higher than the left (Table 3.17).

Table 3.17. Mean scapula PPS on right and left sides in each group.

Mean scapula PPS, 0-10 scale Actual difference

between sides Right side Left side

R-SM group 2.81 (SD 1.47) 3.07 (SD 1.41) -0.26 (9.3%)

L-SM group 4.44 (SD 2.25) 4.04 (SD 2.01) 0.40 (9.0%)

Abbreviations: PPS = pinprick sensitivity, R-SM = right-sided spinal manipulation, L-SM = left-sided spinal

manipulation, SD = standard deviation.

There was no significant main effect for Side (p = .625, ηP2 = .01). There were no significant

interactions for Time by Group (p = .982, ηP2 = .00), Time by Side (p = .373, ηP

2 = .03), or Time by

Side by Group (p = .468, ηP2 = .03).

3.2.8. Forehead Pinprick Sensitivity


with a weak effect size (ηP2 = .10). Post-hoc tests revealed significant differences with weak

effect sizes between forehead PPS at baseline and 10min, baseline and 20min, and baseline and

30min, but not between baseline and immediately after SM. The data indicate that forehead

PPS decreased significantly over time from baseline to 10min, 20min and 30min, by 10.8%,

14.8% and 13.1% respectively (Table 3.18 and Figure 3.10).

57

Table 3.18. Mean forehead PPS at baseline, immediately after intervention, and at 10, 20, and 30

minutes.

Mean forehead PPS, 0-

10 scale

Actual difference compared to Baseline

(% difference)


Baseline 4.81 (SD 2.11) - -

Immediate 4.68 (SD 2.17) 0.13 (2.7%) .447 (ηP2 .02)

10min 4.29 (SD 2.03) 0.52 (10.8%) .039* (ηP2 .13)

20min 4.10 (SD 1.98) 0.71 (14.8%) .007* (ηP2 .20)

30min 4.18 (SD 2.26) 0.63 (13.1%) .049* (ηP2 .12)


There was a significant main effect for Side (p = .001) with a moderate effect size (ηP2 = .29). The

mean forehead PPS on the right was 4.63 (SD 2.09), and on the left was 4.19 (SD 1.85). This

indicates that forehead PPS was significantly higher on the right than the left, with a difference

of 0.44.

Forehead PPS over time

Time


PP

S (

0-1

0 s

ca

le)

0

1

2

3

4

5

6

7

8

* * *

Figure 3.10. Mean forehead PPS at baseline, immediately after intervention, and at 10, 20, and 30


There was no significant interaction for Time by Side (p = .405, ηP2 = .03). However, contrasts

revealed a significant difference between baseline and 30min with a weak effect size. There

were no significant differences between baseline and immediately after SM, baseline and

58

10min, or baseline and 20min. The data indicate that there was a significant difference where

the difference between right and left forehead PPS at baseline was significantly smaller than the

difference at 30min (Table 3.19).

Table 3.19. Mean forehead PPS on the right and left sides at baseline, immediately after intervention,


Mean forehead PPS, 0-10 scale Actual difference

between sides (%

difference)

p-value for diff-

erence compared to

Baseline Right side Left side

Baseline 4.94 (SD 2.24) 4.68 (SD 2.06) 0.26 (5.3%) -


10min 4.44 (SD 2.31) 4.15 (SD 1.93) 0.29 (6.5%) .899 (ηP2 .00)

20min 4.38 (SD 2.19) 3.82 (SD 1.96) 0.56 (12.8%) .248 (ηP2 .04)

30min 4.50 (SD 2.37) 3.85 (SD 2.25) 0.65 (14.4%) .043* (ηP2 .12)


There was no main effect for Group (p = .177, ηP2 = .06). There were no significant interactions

for Time by Group (p = .820, ηP2 = .01), Side by Group (p = .178, ηP

2 = .06), or Time by Side by

Group (p = .837, ηP2 = .01).

3.2.9. Ipsilateral vs. Contralateral Changes

The relationship between the side of SM and changes to the ipsilateral and contralateral side

were analysed using paired t-tests, comparing baseline to each time point.

In the calf, there was a trend toward greater increases in PPT on the side ipsilateral to the side

of SM in both groups (Table 3.20 and Figure 3.11). After R-SM, no differences reached

significance, though the mean increases in PPT were consistently greater on the ipsilateral side

than the contralateral side. After L-SM, the ipsilateral calf PPT increased significantly from

baseline to all time points. The contralateral side also tended to increase, but was not significant.

59

Table 3.20. Paired t-test results for calf PPT in each group on the ipsilateral and contralateral sides,

comparing baseline to immediately after intervention, and to 10, 20, and 30 minutes.

p-value (PPT mean difference in kg/cm2)

R-SM group L-SM group

Ipsilateral, right

calf

Contralateral, left

calf

Ipsilateral, left

calf

Contralateral, right

calf

Baseline vs. Immediate

.090 (0.34) .513 (0.16) .049* (0.38) .657 (0.16)

Baseline vs. 10min

.109 (0.45) .980 (0.01) .006* (0.57) .153 (0.37)

Baseline vs. 20min

.115 (0.48) .576 (0.16) .007* (0.76) .198 (0.42)

Baseline vs. 30min

.178 (0.39) .999 (0.00) .010* (0.71) .058 (0.60)


spinal manipulation, * = p ≤ .05.

Calf PPT per group, side and time (ipsilateral vs. contralateral)

R-SM Ipsi Calf R-SM Contra Calf L-SM Ipsi Calf L-SM Contra Calf

PP

T (

kg

/cm

2)

0

1

2

3

4

5

6

7


**

* *

Figure 3.11. Mean calf PPT after R-SM on the ipsilateral side (right calf), R-SM on the contralateral side

(left calf), L-SM on the ipsilateral side (left calf), and L-SM on the contralateral side (right calf), at

baseline, immediately after intervention, and at 10, 20, and 30 minutes, with standard error bars.


spinal manipulation, Ipsi = ipsilateral, Contra = contralateral, * = p ≤ 0.05.

In the lumbar spine, the trend was less clear. After R-SM, ipsilateral lumbar spine PPT increased

significantly from baseline to 20min and 30min. The contralateral side also tended to increase,

but this was not significant and the increases were smaller than ipsilateral PPT. After L-SM, both

sides of the lumbar spine increased by similar amounts, reaching significance on the ipsilateral

60

side at 30min, and on the contralateral side at 20min and 30min. So for R-SM, lumbar spine PPT

tended to increase more on the ipsilateral than contralateral side, while L-SM resulted in similar

increases on both the ipsilateral and contralateral side of the lumbar spine (Table 3.21 and

Figure 3.12).

Table 3.21. Paired t-test results for lumbar spine PPT in each group on the ipsilateral and contralateral

sides, comparing baseline to immediately after intervention, and to 10, 20, and 30 minutes.


R-SM L-SM

Ipsilateral, right

lumbar spine

Contralateral, left

lumbar spine

Ipsilateral, left

lumbar spine


lumbar spine

Baseline vs. Immediate

.110 (0.55) .706 (-0.14) .381 (0.30) .437 (0.21)

Baseline vs. 10min

.142 (0.67) .624 (0.14) .073 (0.61) .178 (0.47)

Baseline vs. 20min

.043* (0.92) .343 (0.39) .117 (0.48) .008* (0.60)

Baseline vs. 30min

.048* (0.99) .313 (0.50) .033* (0.69) .019* (0.90)



Lumbar PPT per group, side and time (ipsilateral vs. contralateral)

R-SM Ipsi Lumbar R-SM Contra Lumbar L-SM Ipsi Lumbar L-SM Contra Lumbar

PP

T (

kg

/cm

2)

0

1

2

3

4

5

6

7

8

9

10


* *

* **

Figure 3.12. Mean lumbar spine PPT after R-SM on the ipsilateral side (right lumbar spine), R-SM on

the contralateral side (left lumbar spine), L-SM on the ipsilateral side (left lumbar spine), and L-SM on

the contralateral side (right lumbar spine), at baseline, immediately after intervention, and at 10, 20,

and 30 minutes, with standard error bars. Abbreviations: PPT = pressure pain threshold, R-SM = right-

sided spinal manipulation, L-SM = left-sided spinal manipulation, Ipsi = ipsilateral, Contra = contralateral,

* = p ≤ 0.05.

61

After R-SM, scapula PPT increases were quite small overall, and tended to be slightly greater on

the contralateral side. After L-SM, there was a significant ipsilateral increase from baseline to

20min, but otherwise the differences were small and inconsistent for both ipsilateral and

contralateral scapula PPT changes. No real trends can be identified for scapula PPT (Table 3.22

and Figure 3.13).

Table 3.22. Paired t-test results for scapula PPT in each group on the ipsilateral and contralateral

sides, comparing baseline to immediately after intervention, and at 10, 20, and 30 minutes.



Ipsilateral, right

scapula

Contralateral, left

scapula

Ipsilateral, left

scapula


scapula

Baseline vs.

Immediate .621 (0.09) .190 (0.18) .786 (0.05) .080 (-0.38)

Baseline vs.

10min .314 (0.31) .225 (0.31) .527 (-0.10) .380 (-0.10)

Baseline vs.

20min .506 (0.19) .824 (-0.06) .043* (0.31) .984 (-0.00)

Baseline vs.

30min .971 (0.01) .400 (0.24) .741 (0.07) .928 (0.02)



Scapula PPT per group, side and time (ipsilateral vs. contralateral)

R-SM Ipsi Scapula R-SM Contra Scapula L-SM Ipsi Scapula L-SM Contra Scapula

PP

T (

kg

/cm

2)

0

1

2

3

4

5

6

7


*

Figure 3.13. Mean scapula PPT after R-SM on ipsilateral side (right scapula), R-SM on contralateral

side (left scapula), L-SM on ipsilateral side (left scapula), and L-SM on contralateral side (right

scapula), at baseline, immediately after intervention, and at 10, 20, and 30 minutes, with standard

error bars. Abbreviations: PPT = pressure pain threshold, R-SM = right-sided spinal manipulation, L-SM =

left-sided spinal manipulation, Ipsi = ipsilateral, Contra = contralateral, * = p ≤ 0.05.

62

At the forehead, there were no significant PPT differences in either group, and ipsilateral and

contralateral changes tended to be very small (Table 3.23).

Table 3.23. Paired t-test results for forehead PPT in each group on the ipsilateral and contralateral




Ipsilateral, right

forehead

Contralateral, left

forehead

Ipsilateral, left

forehead


forehead

Baseline vs.

Immediate .335 (-0.09) .299 (0.10) .430 (0.09) .316 (0.15)

Baseline vs.

10min .989 (-0.00) .634 (0.07) .451 (0.07) .377 (0.12)

Baseline vs.

20min .508 (-0.07) .332 (0.13) .459 (0.11) .801 (0.04)

Baseline vs.

30min .798 (0.04) .546 (0.09) .397 (0.10) .368 (0.12)


spinal manipulation.

No ipsilateral vs. contralateral trends were noted for PPS in the calf, lumbar spine, scapula or

forehead (Tables 3.24 – 3.27).

Table 3.24. Paired t-test results for calf PPS in each group on the ipsilateral and contralateral sides,

comparing baseline to immediately after intervention, and at 10, 20, and 30 minutes.

p-value (PPS mean difference [0-10 scale])


Ipsilateral, right

calf

Contralateral, left

calf

Ipsilateral, left

calf


calf

Baseline vs.

Immediate .548 (0.18) .868 (0.6) .999 (0.00) .517 (-0.29)

Baseline vs.

10min .854 (-0.06) .791 (-0.12) .868 (-0.06) .370 (-0.35)

Baseline vs.

20min .275 (-0.41) .083 (-0.71) .064 (-0.82) .636 (-0.18)

Baseline vs.

30min .385 (-0.29) .043* (-0.77) .158 (-0.65) .120 (-0.82)


manipulation, * = p ≤ .05.

63

Table 3.25. Paired t-test results for lumbar PPS in each group on the ipsilateral and contralateral sides,

comparing baseline to immediately after intervention, and at 10, 20, and 30 minutes.



Ipsilateral, right

lumbar spine

Contralateral, left

lumbar spine

Ipsilateral, left

lumbar spine


lumbar spine

Baseline vs.

Immediate .110 (-0.65) .616 (-0.18) .018* (-0.82) .011* (-0.94)

Baseline vs.

10min .049* (-0.82) .024* (-1.06) .038* (-0.77) .034* (-0.82)

Baseline vs.

20min .060 (-0.88) .086 (-0.59) .060 (-0.88) .004* (-0.94)

Baseline vs.

30min .019* (-1.00) .065 (-0.88) .003* (-1.29) .006* (-1.18)



Table 3.26. Paired t-test results for scapula PPS in each group on the ipsilateral and contralateral




Ipsilateral, right

scapula

Contralateral, left

scapula

Ipsilateral, left

scapula


scapula

Baseline vs.

Immediate .064 (-0.82) .636 (0.18) .783 (-0.12) .483 (-0.29)

Baseline vs.

10min .090 (-0.82) .743 (-0.12) .029* (-0.71) .311 (-0.29)

Baseline vs.

20min .037* (-0.65) .999 (0.00) .203 (-0.47) .203 (-0.41)

Baseline vs.

30min .124 (-0.71) .999 (0.00) .311 (-0.29) .332 (-0.35)



Table 3.27. Paired t-test results for forehead PPS in each group on the ipsilateral and contralateral




Ipsilateral, right

forehead

Contralateral, left

forehead

Ipsilateral, left

forehead


forehead

Baseline vs.

Immediate .608 (-0.12) .332 (-0.24) .605 (-0.18) .999 (0.00)

Baseline vs.

10min .132 (-0.53) .046* (-0.59) .347 (-0.47) .227 (-0.47)

Baseline vs.

20min .203 (-0.47) .126 (-0.59) .037* (-1.12) .069 (-0.65)

Baseline vs.

30min .227 (-0.47) .018* (-0.94) .210 (-0.71) .436 (-0.41)



64

4. Discussion

The key results are summarised in Table 4.1, and the significance of our findings is discussed

here-in.

Table 4.1. Summary of key results.

Pressure Pain Threshold

1. Calf PPT increased significantly at 20 and 30 minutes.

2. Lumbar spine PPT increased significantly at 10, 20 and 30 minutes.

3. Scapula and forehead PPT showed no significant change.

4. Trend toward greater ipsilateral increase in PPT at the calf and lumbar spine.

Pinprick Sensitivity

1. Calf PPS decreased significantly at 20 and 30 minutes.

2. Lumbar spine PPS decreased significantly immediately, and at 10, 20 and 30 minutes.

3. Scapula PPS decreased significantly at 10 and 20 minutes.

4. Forehead PPS decreased significantly at 10, 20 and 30 minutes.

5. No differences in ipsilateral vs. contralateral PPS changes.

Abbreviations: PPT = pressure pain threshold, PPS = pinprick sensitivity.

4.1. Baseline Characteristics

Several baseline differences between groups were noted in the present study. Firstly, the

proportion of right- and left-hand dominant participants was different between groups.

Secondly, scapula PPS was higher by 1.3 (on an NRS) in the L-SM group. As no significantly

relevant between-group differences were observed, these are considered unlikely to be of

importance.

Across all participants, baseline asymmetry was observed in PPT and PPS, which is inconsistent

with previous literature. Limited research has found no systematic differences in PPT between

the right and left sides of the body, and no differences related to hand dominance (Cathcart and

Pritchard 2006; Fischer 1987; Park et al. 2011). The differences we observed could relate to

participant handedness or methodological decisions (e.g. the left side was always measured

before the right). Only seven of 34 participants in the present study were left-hand dominant,

65

thus we were unable to reasonably explore the relationship between handedness and baseline

pain sensitivity, or changes following SM.

The baseline PPT measures in the present study are mostly consistent with other literature. Calf

muscle PPT was slightly higher than that found in the all-female population studied by Lacourt,

Houtveen, and van Doornen (2012), though PPT tends to be lower in females than in males

(discussed in section 1.3). Lumbar paraspinal muscle PPT at baseline was similar to several prior

studies (Cote, Mior, and Vernon 1994; de Oliveira et al. 2013; Lacourt, Houtveen, and van

Doornen 2012), but was lower compared to two others (Gay et al. 2014; Potter, McCarthy, and

Oldham 2006). Park et al. (2011) reports an almost identical infraspinatus baseline PPT, and a

systematic review by Andersen et al. (2015) found similar but slightly higher forehead PPT

compared to the present study. There does not appear to be any literature with baseline PPS

measures to compare to our data.

4.2. Pressure Pain Threshold

Increases in PPT over time were observed at both the calf and the lumbar spine. At both sites,

PPT tended to continue to increase successively at each time point, becoming significant

compared to baseline at 20 and 30 minutes at the calf, and at 10, 20, and 30 minutes in the

lumbar spine. This suggests that apparent hypoalgesia developed over a period of 10 - 20

minutes in the lower limb and lumbar spine, and was maintained at 30 minutes.

However, the increases were small with weak effect sizes. The minimum detectable change

(MDC) for PPT has been calculated in several studies. For within-day change in spinal muscles,

an MDC of 3.00 kg/cm2 (35 - 40% change) has been proposed (Potter, McCarthy, and Oldham

2006). For two non-spinal muscles an MDC of 1.16 - 1.57 kg/cm2 (roughly 45% change) is

reported, though this is for between-day measures (Walton et al. 2011). Similarly, Bisset, Evans,

and Tuttle (2015) report an MDC of 1.64 kg/cm2 (35 - 50% change) based on inter-rater

66

measurements. The absolute MDC varies depending on the region being tested (Walton et al.

2011), thus percentage changes may represent a more appropriate indicator of change. We

noted increases over time that were well below the suggested actual and percentage MDCs, of

between 0.43 and 0.77 kg/cm2 (7.2 - 11.8% change). This suggests the observed changes in PPT

could be due to chance or measurement error, or real but small changes.

The absence of a control group limits the strength of the conclusions. However, PPT has been

shown to be robust to repeated measurement and reliable within-day to change (Potter,

McCarthy, and Oldham 2006). That we observed increased PPT following SM in the calf and

lumbar spine, but not in the scapula or forehead, supports the argument for a treatment effect

in this study even when considering the limitations (discussed further below).

In comparison to other literature, the PPT changes we observed are consistent with changes

seen following cervical SM. Cervical SM consistently produces hypoalgesia locally (in the cervical

spine) and in the upper limb, but not the lower limb (Coronado et al. 2012). Thus our study

supports the notion of local and segmental hypoalgesia in response to SM, i.e. at the site of

manipulation and at peripheral sites innervated by that spinal area.

However, our results conflict with similar studies in the lumbar spine. Others found no significant

changes to lumbosacral or lower limb PPT following lumbar SM (Cote, Mior, and Vernon 1994;

de Oliveira et al. 2013; Gay et al. 2014; Thomson, Haig, and Mansfield 2009), or a small but

significant decrease (Orakifar et al. 2012). There is little consistency in the site of PPT testing,

and variably involved the lumbar paraspinal muscles, over a lumbar spinous process, the

sacroiliac joint, or sacrum. This may account for some of the differences compared to the

present study. Other possible explanations include differing sample populations (e.g. chronic

LBP), a potential confounding effect of other outcome measures, and a particularly small sample

size in one study.

67

As we found no significant immediate increases in PPT at the calf and lumbar spine (though there

is an upward trend), our study suggests that changes in PPT following lumbar SM develop over

a 10 - 20 minute period. Three of the five studies in the lumbar spine measured only immediate

PPT changes so this effect may have been missed. Cote, Mior, and Vernon (1994) did show an

upward trend in PPT over time, which did not reach significance. Orakifar et al. (2012) found

that PPT decreased at 10 and 15 minutes, which is contrary to any other studies in the lumbar

or cervical spine, and this could possibly be explained as a confounding effect of measuring the

Hoffman reflex, involving electrical stimulation of a peripheral nerve, prior to measuring PPT.

Two cervical spine studies showed increases in PPT were not sustained at 30 minutes or two

hours (Hamilton, Boswell, and Fryer 2007; Molina-Ortega et al. 2014). The present study adds

to this literature by suggesting that lumbar SM leads to a gradual increase in PPT over time that

is maintained at 30 minutes.

The significant disparity observed in studies of PPT following cervical SM vs. lumbar SM is

curious. Our study is the first to refute such disparity, and the reason for the differences in other

studies remains speculative. Orakifar et al. (2012) have suggested various possibilities, including

differences in the density of mechanoreceptors and nociceptors in the cervical and lumbar

regions, differences in baseline PPT between regions, and region-specific differences in the

physiologic response to SM. Methodologic decisions may also play a role.

More broadly, it appears that mobilisation of spinal and extremity joints also elicits a hypoalgesic

response that is local and possibly remote to the site of intervention (Voogt et al. 2015),

including following lumbar mobilisation (Krouwel, Hebron, and Willett 2010; Willett, Hebron,

and Krouwel 2010). This lends strength to the theory that lumbar SM does in fact cause

hypoalgesia, as suggested by our findings.

68

The trend toward greater PPT increases at the calf and lumbar spine ipsilateral to the SM is in

contrast to the limited literature in this area (see section 1.3.1.4). At present it appears that PPT

tends to increase more on the same side as the participant’s dominant hand based on limited

studies. The actual changes in PPT we observed were small, and there may have been

insufficient power to accurately detect asymmetry between groups in this manner, so the

present findings should be regarded with caution. As already stated, we recruited insufficient

left-hand dominant participants to investigate the effect of hand dominance on pain sensitivity

changes.

4.3. Pinprick Sensitivity

The observed decreases to PPS represent a reduction in pain sensitivity, seen at all sites at

various times. As PPS is a novel and unvalidated measure of superficial pain sensitivity, the

observed changes may represent a global treatment effect, a learned effect, or an

acclimatisation to PPS measurements. The pattern of change suggests a non-specific effect

unrelated to the SM.

For PPS, there is no defined MDC with which to compare our results. A 30% change in PPS may

be a reasonable approximation based on prior research investigating the minimum clinically

important difference of self-reported pain intensity using a numeric rating scale (Hawker et al.

2011). It may also be reasonable to expect changes of a similar magnitude to PPT MDC, in the

vicinity of 35-50% change. Our study observed PPS to decrease between 9.8 and 22.5%, which

reaches neither of these estimations. The effect sizes were weak to moderate. For the above

reasons, we speculate that PPS is not a relevant measure of hypoalgesia following SM.

4.4. Interpretation

A significant hurdle is that the clinical relevance of PPT and PPS is as yet unclear. Reduced PPT

has been observed in numerous painful conditions and is thought to represent an individual’s

69

sensitivity to pain; it thus may be likely to relate to clinical features such as self-reported pain

intensity and disability (Hübscher et al. 2013). A recent systematic review and meta-analysis

concluded that there was no significant correlation between pain thresholds and pain intensity

or disability, across a variety of factors including pain condition (e.g. LBP, neck pain), acute or

chronic status, and local or remote testing site (Hübscher et al. 2013). Studies published since

have found conflicting results (Fernández-Pérez et al. 2012; Gonçalves et al. 2015; Uddin et al.

2014). Variable findings may reflect differing aetiologies, chronicity, and other factors. Two

studies have however suggested that PPT may be adequately responsive to change for use as a

clinical outcome measure in some situations (Goolkasian, Wheeler, and Gretz 2002; Walton et

al. 2014). PPS does not appear to have been studied in this capacity.

It is thus unclear whether PPT may be used clinically as a valid and reliable tool in

musculoskeletal pain. Determining the clinical implications of PPT in particular, which is widely

used in manual therapy research, is of paramount importance. It should be determined if any

correlations do in fact exist between PPT and self-reported pain or disability in various painful

conditions, or if there are correlations with other clinical features such as symptom pattern, as

well as whether PPT can be used reliably as a clinical outcome measure.

Though direct evidence is lacking, we speculate that the selective hypoalgesia we observed

following SM helps to explain some of the clinical pain relief associated with SM. Short- or

medium-term hypoalgesia is potentially highly valuable in patients receiving SM, where we often

wish to encourage early return to activity in order to aid recovery. Segmental hypoalgesia could

also be beneficial in the management of painful conditions in the upper and lower limb, allowing

us to use targeted SM to enhance pain relief.

When considering the neurophysiological theories, our results are consistent with the theory

suggesting descending inhibitory pain control systems are involved in post-SM hypoalgesia. As

70

discussed in section 1.3.7.1, activation of the PAG appears to inhibit C-fibre nociceptive signals,

leaving Aδ-fibre signals unaffected. PPT (which is mediated by both fibre types) revealed

hypoalgesia in response to SM, while PPS (mediated only by Aδ-fibres) showed a global change

that we speculate is unrelated to the SM. In addition, Moss, Sluka, and Wright (2007) point out

that such supraspinal mechanisms are likely to produce a more widespread response, not just

local to the inciting stimulus. Thus the changes we observed are consistent with the mechanism

through which descending pain inhibition is carried out.

It is known that the descending pain control system is involved in the development of chronic

pain states and central sensitisation through imbalance of descending facilitatory and inhibitory

signals (Heinricher et al. 2009). Additionally, C-fibre inputs contribute to dorsal horn neuron

sensitisation (Heinricher et al. 2009). If, as speculated, SM triggers descending inhibition that

suppresses C-fibre activity, SM could play a valuable role in treating and preventing chronic pain

states.

The pain gate theory (see section 1.3.7.2) likely only accounts for short-term hypoalgesia, as the

gating effect only lasts for as long as the non-nociceptive stimulus is present (Kotzé and Simpson

2008). Primarily C-fibre nociceptive signals are inhibited, but as we observed local and lower

limb PPT changes that persisted for at least 30 minutes, the pain gate is a less likely explanation

for this.

Why hypoalgesia was observed locally in the lumbar spine and segmentally in the lower limb,

but not at the shoulder or forehead, is unclear from a neurophysiologic perspective. Some dorsal

horn neurons receiving sensory input from the lumbar spine and lower limb would be expected

to be anatomically close to one another (in the spinal cord), while those receiving input from

the shoulder and forehead are anatomically remote. Thus it is possible that the underlying

neurophysiologic mechanism alters pain processing regionally in the spinal cord.

71

It is known that the descending pathways are capable of acting on select regions of the dorsal

horn (Millan 2002), and that serotonin and noradrenaline mediate inhibition primarily through

volume transmission (the diffusion of neurotransmitters from a synapse to remote sites) which

results in more widespread effects (Todd 2010). Thus once again the descending inhibitory pain

pathways may offer a plausible explanation for the observed phenomena.

4.5. Limitations

There are various limitations to the present study. Firstly, it is possible that measuring PPS had

a confounding effect upon PPT. PPS was always measured after PPT, followed by a period of rest

before the next follow-up measures were taken, though a confounding effect may still have

occurred. Anxiety is a known confounder to pain (Rhudy and Meagher 2000), which was not

controlled for in this study other than with a thorough informed consent process and by assuring

participants that the SM procedure was unlikely to cause pain. Participants may have

experienced anxiety in relation to the induction of experimental pain or to receiving SM

(especially in those who had not had SM previously). Alternatively, some participants may have

been experiencing anxiety for unrelated reasons.

The use of young asymptomatic participants limits the generalisability of the results to

symptomatic and older populations, and future research should explore this. In particular,

chronic pain patients may respond differently as a result of central sensitisation. The lack of a

sham group also means some of the effect may be explained by placebo or other effects, such

as the positioning involved in the SM procedure or physical touch. These could each have a

confounding effect, hence a non-thrust manual contact control group would have been valuable

to account for some of this effect. Finally, the study was adequately powered to detect large

main effects at each location, however the study is likely underpowered to adequately detect

72

small changes, and changes for the more complex two- and three-way interactions. Thus we

may be committing some type II errors.

5. Conclusion

This study set out to investigate the effects of lumbar SM on local and remote pain perception

using two measures of experimental pain. As a commonly used manual therapy technique for

musculoskeletal pain, understanding the neurophysiologic effect of SM is imperative. Thus, we

sought to answer the following questions:

1) Does lumbar SM affect pain sensitivity (deep and superficial) at local and remote

locations?

2) Do changes last for at least 30 minutes?

3) Are any changes related to the side of manipulation (i.e. bilateral symmetric or

asymmetric)?

We conclude that lumbar SM does lead to increased PPT (reduced deep pain sensitivity) in the

lumbar spine and in the lower limb for at least 30 minutes, with no changes at superior sites,

despite the limitations. This implies a local and segmental selective hypoalgesia in response to

lumbar SM. The hypoalgesia may be slightly greater on the side ipsilateral to the SM, but this is

unclear.

We also conclude that PPS, considered to represent superficial pain sensitivity, does not change

as a specific response to lumbar SM.

Our findings align with the theory that post-SM hypoalgesia is mediated by supraspinal

mechanisms, namely descending inhibitory pain control. Activation of the pain gate mechanism,

altered dorsal horn excitability, and placebo and psychosocial factors may also be involved.

73

The findings may explain some of the clinical value of SM, and highlight intriguing potential for

the targeted use of SM for painful conditions including chronic pain states. It is particularly

important now that the clinical relevance of PPT be established in order to enhance the clinical

application of SM. If any relationships do exist between PPT and clinical features, it is a

potentially valuable clinical outcome measure.

As the first study to observe post-SM hypoalgesia in the lumbar spine, we highlight the

importance of future research to clarify whether lumbar SM has a similar effect on pain

sensitivity as cervical SM.

Studies following PPT beyond 30 minutes, and comparing whether responses differ between

symptomatic and asymptomatic populations would also be valuable. Additionally, it is important

that the neurophysiologic mechanism for post-SM hypoalgesia is determined as direct human

evidence is lacking.

74

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Appendix A – Participant Checklist and Medical History Questionnaire

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Appendix B – Information Letter

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Appendix C – Consent Form

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Appendix D – Shapiro-Wilk tests for Normality Results

1. Tests of Normality for Pressure Pain Threshold

Group (side of manipulation)

Shapiro-Wilk

Statistic df Sig.

PPT Left Calf at Baseline Right .935 17 .266

Left .853 17 .012*

PPT Right Calf at Baseline Right .885 17 .039*

Left .932 17 .239

PPT Left Lumbar at Baseline Right .916 17 .124

Left .828 17 .005*

PPT Right Lumbar at Baseline Right .945 17 .385

Left .810 17 .003*

PPT Left Shoulder at Baseline Right .914 17 .116

Left .895 17 .057

PPT Right Shoulder at Baseline Right .929 17 .207

Left .959 17 .616

PPT Left Forehead at Baseline Right .940 17 .318

Left .968 17 .787

PPT Right Forehead at Baseline Right .921 17 .152

Left .922 17 .160

PPT Left Calf at Immediate Right .947 17 .418

Left .808 17 .003*

PPT Right Calf at Immediate Right .913 17 .112

Left .812 17 .003*

PPT Left Lumbar at Immediate Right .955 17 .538

Left .907 17 .090

PPT Right Lumbar at Immediate Right .919 17 .144

Left .832 17 .006*

PPT Left Shoulder at Immediate Right .957 17 .568

Left .841 17 .008*

PPT Right Shoulder at Immediate Right .919 17 .144

Left .894 17 .054

PPT Left Forehead at Immediate Right .911 17 .105

Left .887 17 .041*

PPT Right Forehead at Immediate Right .962 17 .669

Left .790 17 .001*

PPT Left Calf at 10min Right .885 17 .038*

Left .810 17 .003*

PPT Right Calf at 10min Right .906 17 .087

Left .922 17 .158

PPT Left Lumbar at 10min Right .899 17 .066

Left .947 17 .411

PPT Right Lumbar at 10min Right .915 17 .121

Left .889 17 .045*

PPT Left Shoulder at 10min Right .958 17 .598

Left .898 17 .064

PPT Right Shoulder at 10min Right .885 17 .038*

Left .917 17 .134

PPT Left Forehead at 10min Right .937 17 .283

Left .902 17 .072

PPT Right Forehead at 10min Right .974 17 .890

Left .825 17 .005*

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PPT Left Calf at 20min Right .911 17 .106

Left .798 17 .002*


Left .873 17 .024*


Left .904 17 .080


Left .875 17 .026*


Left .916 17 .127

PPT Right Shoulder at 20min Right .909 17 .095

Left .933 17 .240


Left .878 17 .029*


Left .821 17 .004*

PPT Left Calf at 30min Right .899 17 .066

Left .779 17 .001*


Left .897 17 .061


Left .931 17 .224


Left .871 17 .023*


Left .960 17 .624

PPT Right Shoulder at 30min Right .926 17 .185

Left .971 17 .839


Left .926 17 .185


Left .852 17 .012*

Abbreviations: PPT = pressure pain threshold, * = significant (≤ .05).

2. Tests of Normality for Pinprick Sensitivity

Group (side of manipulation)

Shapiro-Wilk

Statistic df Sig.

PPS Left Calf at Baseline Right .939 17 .308

Left .961 17 .656

PPS Right Calf at Baseline Right .888 17 .043*

Left .931 17 .225

PPS Left Lumbar at Baseline Right .869 17 .021*

Left .946 17 .391

PPS Right Lumbar at Baseline Right .937 17 .285

Left .952 17 .483

PPS Left Shoulder at Baseline Right .893 17 .052

Left .946 17 .401

PPS Right Shoulder at Baseline Right .869 17 .021*

Left .949 17 .445

PPS Left Forehead at Baseline Right .960 17 .631

Left .922 17 .157

PPS Right Forehead at Baseline Right .952 17 .484

Left .929 17 .213

PPS Left Calf at Immediate Right .914 17 .115

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Left .952 17 .487

PPS Right Calf at Immediate Right .960 17 .639

Left .913 17 .110

PPS Left Lumbar at Immediate Right .946 17 .402

Left .902 17 .074

PPS Right Lumbar at Immediate Right .892 17 .050*

Left .961 17 .642

PPS Left Shoulder at Immediate Right .910 17 .102

Left .930 17 .219

PPS Right Shoulder at Immediate Right .924 17 .172

Left .906 17 .087

PPS Left Forehead at Immediate Right .939 17 .305

Left .962 17 .679

PPS Right Forehead at Immediate Right .911 17 .103

Left .955 17 .539

PPS Left Calf at 10min Right .883 17 .036*

Left .926 17 .183

PPS Right Calf at 10min Right .930 17 .215

Left .948 17 .426

PPS Left Lumbar at 10min Right .946 17 .404

Left .893 17 .051*

PPS Right Lumbar at 10min Right .922 17 .160

Left .924 17 .173

PPS Left Shoulder at 10min Right .910 17 .101

Left .910 17 .100

PPS Right Shoulder at 10min Right .916 17 .124

Left .933 17 .240

PPS Left Forehead at 10min Right .942 17 .337

Left .962 17 .663

PPS Right Forehead at 10min Right .950 17 .449

Left .968 17 .774


Left .896 17 .058


Left .958 17 .593


Left .966 17 .741


Left .961 17 .657


Left .918 17 .136

PPS Right Shoulder at 20min Right .925 17 .180

Left .973 17 .875


Left .950 17 .454


Left .965 17 .727


Left .919 17 .142


Left .934 17 .257


Left .911 17 .103


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Left .955 17 .539


Left .918 17 .137

PPS Right Shoulder at 30min Right .866 17 .019*

Left .909 17 .096


Left .946 17 .402


Left .961 17 .658

Abbreviations: PPT = pressure pain threshold, * = significant (≤ .05).

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THE EFFECT OF LUMBAR SPINAL MANIPULATION UPON LOCAL … · iii Abstract Introduction: The mechanism for pain relief associated with spinal manipulation (SM) is not well understood