Chronic Pain – Mechanisms and Management principles · 2018. 12. 17. · Chronic pain – Pain beyond expected period of healing – Pain no longer serves a useful purpose – Changes

11/12/2018

1

Chronic Pain – Mechanismsand Management principles

Dr Nick Shenker PhD FRCP

Addenbrooke’s Hospital

What is pain?International Association for the Study of Pain

(IASP)

‘An unpleasant sensory andemotional experience associated

with actual or potential tissuedamage, or described in terms of

such damage.’

11/12/2018

2

Pain pathways

Brain neuromatrix

Medulla

Spinal cord: dorsal horn

Nociceptive neurons

Nociception

ThermalMechanical

Chemical

Peripheralsensitisation

Centralsensitisation


LearningNeuroplasticity

11/12/2018

3

Nociception: Transduction

Nociceptors

Mechanoreceptors Polymodal Receptors

Distortion Mechanical Injury ThermalIrritation

Chemical Stimulation

Sensitisation – development ofallodynia

11/12/2018

4

Nociception Transduction

Substance Source Effect on Nerve

Histamine Platelets, mast cells ActivatesBradykinin Plasma ActivatesSubstance P Nerve terminals SensitisesProstaglandins Damaged Cells SensitisesInterleukins Mast cells Activates, sensitisesLeukotrienes Damaged cells SensitisesTNF-α Macrophages Activates, sensitisesProtons Tissue damage Activates

Nociception Transmission

11/12/2018

5

Spinal cord Dorsal horn

Spinal cord Cartesian model

• Pain can be relieved bycounter-irritation

• Gross tissue damage not beaccompanied by pain

• Minor damage results inexquisite ‘burning’ pain

• Phantom limb pain

11/12/2018

6

Spinal cord Gate control

Ronald Melzack Patrick Wall

Gating at the spinal cord

11/12/2018

7

Spinal cord. Wind-up.

Neuroanatomy of Pain______________________________________________________________________________

11/12/2018

8

Acute pain neuromatrix


11/12/2018

9



11/12/2018

10



11/12/2018

11


Recap

• Nociception• Peripheral Sensitisation• Spinal gate• Brain pathways• Descending systems

11/12/2018

12

Spinal cord Descendingsystems

• Serotonergic

• Adrenergic

• Opioid– Diffuse Noxious

Inhibitory Control(DNIC)

Spinal cord Descendingsystems

11/12/2018

13

Development of chronic pain

• Acute pain– Usually obvious tissue damage– Protective function– Increased nervous system

activity1

– Pain resolves upon healing

1. Woolf CJ, Costigan M. Proc Natl Acad Sci U S A. 1999;96:7723-30. 2. Woolf CJ, Max MB. Anesthesiology.2001;95:241-9.

Chronic pain– Pain beyond expected period of

healing– Pain no longer serves a useful purpose– Changes in pain signalling and

detection2

– Degrades health and function

Chronic pain has systemicconsequences

Functional Domain Stress Responses to Pain Examples of Clinical Manifestations

Endocrine/metabolic Altered release of multiple hormones (e.g.,ACTH, cortisol, catecholamines, insulin) withassociated metabolic disturbances

Weight lossFeverIncreased respiratory and heart rateShockIncreased blood sugar

Cardiovascular Increased heart rateIncreased vascular resistanceIncreased blood pressureIncreased myocardial oxygen demandHypercoagulation

Unstable anginaMyocardial infarctionDeep vein thrombosis

Respiratory Decreased air flow due to involuntary (reflex musclespasm) and voluntary (“splinting”) mechanisms thatlimit respiratory effort

AtelectasisPneumonia

Gastrointestinal Decreased rate of gastric emptyingDecreased intestinal motility

Delayed gastric emptying, constipation,anorexia, ileus

Musculoskeletal Muscle spasmImpaired muscle mobility and function

ImmobilityWeaknessFatigue

Immune Impaired immune function Infection

Genitourinary Abnormal release of hormones that affect urineoutput, fluid volume, and electrolyte balance

Decreased urine outputHypertension (fluid retention)Electrolyte disturbances

11/12/2018

14

Brain neuromatrix

Medulla


Nociceptive neurons

Nociception

ThermalMechanical

Chemical

Anatomy

Structured approach to the patient in chronic painHague, Shenker, BERH, 2015

Brain neuromatrix

Medulla


Nociceptive neurons

Nociception

ThermalMechanical

Chemical





Physiology Anatomy

Injury


11/12/2018

15

Brain neuromatrix

Medulla


Nociceptive neurons

Nociception

ThermalMechanical

Chemical





Physiology Anatomy

Injury


Age <40

DepressionHigh anxiety traitLess perceived Social Support“Anger style” of emotional regulation>1 year duration

Pain report >4/10Altered body scheme (dysynchiria)>1 limb affected

Post-operative complicationsCold limb presentation

Leg affected (vs arm)Severity of injury

Brain neuromatrix

Medulla


Nociceptive neurons

Nociception

ThermalMechanical

Chemical





Sleep, Depression, Anxiety

Alterations in body scheme, functional status

Allodynia, hyperalgesia, neuropathic paindescriptions

Signs of inflammation, altered structure

Physiology Anatomy Clinical Assessment

Figure 2. Structured approach to the patient in chronic pain

11/12/2018

16

Figure 3. Diagnoses associated with chronic pain





Clinical Assessment

Degenerative and MSK diseaseincluding Immune mediatedinflammatory disease ( eg RA, AS etc)

Chronic infectionPost-surgicalPost-traumatic

Compression neuropathy(e.g. sciatica, CTS)

Peripheral neuropathy(e.g. diabetes)

Central nervous lesions(e.g. stroke,Parkinson’s, MS)

Central nervous dysfunction(e.g. fibromyalgia, CRPS, chronic low back pain,

phantom limb pain)

Endocrine dysfunction(e.g. Low vit D; thyroidabnormalities)

Figure 3. Diagnoses associated with chronic pain





Clinical Assessment

Degenerative and MSK diseaseincluding Immune mediatedinflammatory disease (e.g. RA, AS, etc)

Chronic infectionPost-surgicalPost-traumatic

Compression neuropathy(e.g. sciatica, CTS)

Peripheral neuropathy(e.g. diabetes)

Central nervous lesions(e.g. stroke,Parkinson’s, MS)

Central nervous dysfunction(e.g. fibromyalgia, CRPS, chronic low back pain,

phantom limb pain)

Endocrine dysfunction(e.g. low vit D; thyroidabnormalities)

11/12/2018

17





Physiology

Injury

Structured approach to the patient in chronic pain





Physiology History

Injury


Psychosocial contributors

QuestionnairesHADNLSQ (depersonalisation)

BPI

Functional questionnairesUEFI/LEFIHAPTSS

Medications –Previously triedDosagesSide Effects

Fracture history

11/12/2018

18





Physiology History

Injury


Psychosocial contributors

QuestionnairesHADNLSQ (depersonalisation)

BPI

Functional questionnairesUEFI/LEFIHAP

TherapiesMedications –

Previously triedDosagesSide Effects

Fracture history

58 year old ladyNormal relationships,money. Nolitigation/insurance workSleep disturbed11/21 Anx ; 4 / 21 Dep3.4/6

3-7/10, average of 5/10

38/80 Upper & 25 /80Lower57/94 Max; 34/94 adjusted

Physiotherapy

NSAID; Codeine;ParacetamolAmitriptyline 10mg





Physiology

Injury


Mood assessmentGuarding / Distraction

Body scheme

AllodyniaHyperalgesia

Limb MovementActive/passive

Site assessmentSkinInflammation

Examination

11/12/2018

19





Physiology

Injury


Mood assessmentGuarding / Distraction

Body scheme

AllodyniaHyperalgesia

Limb MovementActive/passive

Site assessmentSkinInflammation

Examination

Anxious, two crutchesPresent

Abnormal

Allodynia ++Hyperalgesia ++

Hip, knee, ankle OKToes much reduced

Colour and tempasymmetrySwellingNormal sweating, skin,nails

58 year old lady

Importance of early andeffective treatment of pain

• A lower degree of chronicity relates to abetter therapy result1

• Chronic pain is associated withmorphologicalchanges in the CNS 2,3

• Once present, it is often persistent andseldom totally resolves even withtreatment 4

• Chronic pain causes tremendous personalsuffering 5 and marked negative effects onwellbeing and quality of life 6

1 Schulte E et al. Eur J Pain 2010;14:308.e1-308.e10. 2 Tracey I, Bushnell MC. J Pain 2009;10:1113-20.3 Apkarian AV et al. J Neurosci 2004;24:10410-5. 4. Elliott AM et al. Lancet 1999;354:1248–1252. 5. Managementof Chronic pain in Adults, NHS Quality Improvement Scotland 2006. 6. Breivik H et al. Eur J Pain 2006;10:287-333.

11/12/2018

20

Biopsychosocial model

Social

Biological Psychological

Biopsychosocial model

Social

Biological Psychological

11/12/2018

21

Why is a biopsychosocialperspective important?

•

Edwards D et al. Pain Pract 2006;6:242-53.

4 pillars of care

11/12/2018

22

What is patient-centred care?• The term patient-centred care

meansthat healthcare professionals:

• Engage with patients at a deep level,which includes understanding boththeir illness and how it will affect theirlife1

• Take into account the patient’s desirefor information, share decision making,and respond appropriately2

1. Davies PG. J Epidemiol Community Health 2007;61:39. 2. Stewart M. BMJ 2001;322:444-5.

Education of the patient andtheir relatives

• Biopsychosocialpain model

• Basicpharmacology

• Basic anatomy• Weight

management• Information on

relevant painsyndromes

11/12/2018

23

Pharmacological approaches tochronic pain management

• Non-opioid analgesics (e.g. NSAIDs, paracetamol)• Opioid analgesics (e.g. tramadol, codeine, morphine, oxycodone)• Antidepressants (e.g. amytriptyline, duloxetine)• Anticonvulsants (e.g. gabapentin, pregabalin)• Topical analgesics (e.g. capsaicin, lidocaine 5% plaster)

Non-opioid analgesics: NSAIDS• E.g. aspirin, ibuprofen

1. Warner TD, Mitchell JA. FASEB J 2004;18:790-804.

Efficacy Mode of action Side effects

Mainly act onnociceptive pain1

Inhibition ofcyclooxygenase1

Prostaglandinsynthesisdecreases1

GI irritation/bleeding1

Renal toxicity1

Potential drug-druginteractions

Cardiovascularside-effects (Cox-2)1

11/12/2018

24

Other non-opioid analgesics:paracetamol

• Aniline derivative e.g. Panadol

Mattia A, Coluzzi F. Minerva Anestesiol. 2009;75:644-53.


Analgesic andantipyretic effects

Noanti-inflammatoryaction

Inhibition ofcentralprostaglandinsynthesis

Not been fullyexplained

Risk of toxicliver damage

Opioid analgesics• Weak opioids: e.g. tramadol and codeine,

strong opioids: e.g morphine andoxycodone1

1. Hawthorn J & Redmond K (1998) Pain causes and management. Blackwell Science Ltd. 2. Furlan AD et al. CMAJ 2006;174:1589-94.3. Jacobsen R et al. J Opioid Manag 2007;3:207-14.

Efficacy Mode of action1 Side effects2,3

Mainly effectivein nociceptivepain

Less effective inchronic states

Only partiallyeffective inneuropathicpain

Activate theendogenousanalgesic system

- Stimulate receptorsin the limbic systemto eliminatethe subjectivefeeling pain

- Affect descendingpathways thatmodulate painperception

- Reduce ascendingpain signaltransmission in thespinal cord

Nausea

Vomiting

Constipation

Dizziness orvertigo

Somnolence

Dry skin,pruritus

Endogenous pain modulation

11/12/2018

25

Antidepressants: TCAs

• E.g. amytriptyline,imipramine

1. Dworkin RH et al. Arch Neurol. 2003;60:1524-34.


Neuropathicpain1

Complexregional painsyndrome1

Tensionheadache

Inhibition ofneuronal reuptakeof noradrenalineand serotonin(5-HT)

Constipation1

Dry mouth1

Somnolence1

Abnormalitiesin heart rate orrhythm1

Insomnia

Increasedappetite

Antidepressants: Selective serotonin andnoradrenalin reuptake inhibitors (SSRIs & SNRIs)

• E.g. duloxetine, venlafaxine

1. Quilici S et al. BMC Neurol. 2009;9:6. 2. Attal N et al. Eur J Neurol. 2006;13:1153-69.

Efficacy Mode of action Side effects(duloxetine)

Neuropathicpain1,2

SNRIs are betteranalgesics thanSSRIs

Selectively inhibitreuptake ofnoradrenaline orserotonin or both

Provide analgesiaby intensifyingdescendinginhibition

Nausea &Vomiting2

Constipation2

Somnolence1,2

Dry mouth2

Increasedsweating2

Loss of appetite2

11/12/2018

26

Anticonvulsants• E.g. carbamazepine, gabapentin, pregabalin

1. Attal N et al. Eur J Neurol. 2006;13:1153-69. 2.Dworkin RH et al. Arch Neurol. 2003;60:1524-34.3. Ettinger AB, Argoff CE. Neurotherapeutics. 2007;4:75-83.

GabapentinEfficacy Mode of action Side effects

Neuropathicpain1,2

Different modesof action:

Gabapentin: bindsto presynapticvoltage-dependentcalcium channels1

Pregabalin:interacts withspecial N-typecalcium channels1

Carbamazepine:blocks Na+1 andCa2+ channels

Sedation1,2

Dizziness1,2

Ataxia1

Peripheraloedema1,2

Nausea1,2

Weight gain3

Carbamazepine

Pregabalin

Topical analgesics• Main categories of topical analgesics include:

– Rubefacients: traditional formulations based onsalicylate and nicotinate esters, capsaicin andcapsicum extracts and derivatives

– NSAIDs: diclofenac, felbinac, ibuprofen, ketoprofen,piroxicam, naproxen, flurbiprofen and other NSAIDs

– A miscellaneous group: including benzydamine,mucopolysaccharide polysulphate, salicylamideand cooling sprays

– Lidocaine 5% medicated plaster• Topical analgesics reduce pain impulses transmitted by:

– A-delta-fibres– C-fibres

• Main side effects are localised application site reactions, including:1-4

– Rash– Pruritus– Erythema

1. Boots Company PLC. Boots Pain Relief Heat Rub SmPC. January 2008. 2. Diomed DevelopmentsLimited. Ibuleve Gel SmPC. January 2009. 3. Meda Pharmaceuticals. Difflam Cream SmPC. March 2010.4. Grünenthal Ltd. Versatis 5% Medicated Plaster SmPC. September 2009.

11/12/2018

27

Main side effects ofpharmacological treatments

1. Furlan AD et al. CMAJ 2006;174:1589-94. 2. Jacobsen R et al. J Opioid Manag 2007;3:207-14. 3. Warner TD, MitchellJA. FASEB J 2004;18:790-804. 4. Ettinger AB, Argoff CE. Neurotherapeutics 2007;4:75-83. 5. Attal N et al. Eur J Neurol2006;13:1153-69. 6. Dworkin RH et al. Arch Neurol 2003;60:1524-34. 7. Quicili S et al. BMC Neurol 2009;9:6.

Opioids1,2 NSAIDs3

NauseaVomitingConstipationDizziness or vertigoSomnolenceDry skin, pruritus

Gastrointestinal irritation/bleedingRenal toxicityPotential drug-drug interactionsCardiovascular side effects (e.g.myocardial infarction, stroke andhypertension) with some selectiveCox-2 inhibitors

Anticonvulsants4,5,6 SNRIs5,7

SedationDizzinessAtaxiaPeripheral oedemaNauseaWeight gain

NauseaVomitingConstipationSomnolenceDry mouthIncreased sweatingLoss of appetite

Physiotherapy and strengthtraining

• Physiotherapy and strength training aim torelieve pain and improve mobility

• Various methods are used, including:–Massage–Joint mobilisations–Manipulation–Electrotherapy / US

11/12/2018

28

Peripheral stimulation andinterventional therapy

• Peripheral stimulation, e.g.– Transcutaneous electrical nerve

stimulation (TENS)– Acupuncture

• Interventional therapy, e.g.– Nerve blocks– Spinal stimulation– Surgical pain management

Complementary / alternativemedicine

• Some more establishedthan others

eg. Chiropracter, Osteopath, Acupuncture,Homeopathy, Herbal, Aryuvedic

VsBeauty therapy, Colonic hydrotherapy,Colour Breathing, Hopi Ear Candles,ReHarmonising

11/12/2018

29

Clinical assessment• Peripheral (tissue) driver

– OA, soft tissue, nerve damage, inflammation

• Peripheral sensitisation– Allodynia, hyperalgesia

• Central sensitisation– Sleep, systemic features, depersonalisation, body scheme

• Psychosocial– Mood, family, community, housing, benefits, litigation

Conclusions• Pain is complex• Treat tissue damage and pain will go but…

– Some damage is irreversible– Possible that pain exists with no damage

• Chronic pain approach helpful in parallel:– WHO Pain ladder– Adjuncts are useful– Biopsychosocial approach required– Palliate and counsel

11/12/2018

30

Chronic Pain – Mechanismsand Management principles

Dr Nick Shenker PhD FRCP

Addenbrooke’s Hospital

Documents

Chronic Pain – Mechanisms and Management principles · 2018. 12. 17. · Chronic pain – Pain beyond expected period of healing – Pain no longer serves a useful purpose – Changes