A Pain Clinic Approach to Fibromyalgia

Brigitte Gertoberens Pain Medicine SpecialistMalcolm Johnson Clinical PsychologistMurray Hames Senior Physiotherapist

The Auckland Regional Pain Service

Prevalence in the general population is approximately 2

Female Male ratio 71

Most frequently diagnosed in middle aged women prevalence increases with age

Up to 40 of the pain clinic presentations

Wide spread musculoskeletal pains Muscle weakness and tenderness

muscle cramps Unexplained soft tissue swellings Hypersensitivity to touch and

temperature Tingling numbness pins and

needle sensations Disturbed temperature regulation Phono- and photo-hypersensitivity Itch without dermatological or

metabolic pathology

Symptoms are unspecific and variable in time course

Headaches Tinnitus Sleep disturbances Fatigue Poor memory and concentration Irritable bowel and bladder

syndrome Dysmenorrhia Menometrorrhagias TMJ disorder

Co-diagnosis of anxietydepressionPTSD is commonly found

Diagnosis is based on

Taking a profound history including a medicationsubstance use history

a clinical examination with specific attention to tenderness and sensory disturbances and using theACR assessment criteria 2010 plus Fibromyalgia Survey Questionnaire

Exclusion of other sinister pathology

Routine blood tests full blood counts ESR CRP CK Ca TSHRoutine testing for antibodies associated with rheumatoid diseases or lupus not recommended

Widespread Pain Index (0-19)

Pain or tenderness over the past 7 days

Shoulder R L Jaw R L

Upper arm R L Chest

Lower arm R L Abdomen

Hip R L Upper back

Upper leg R L Lower back

Lower leg R L

Symptom Severity Scale (SS scale)

0 (no problem) 1 (mild or intermittent)2 (moderate) 3 (severe)

Over the past week

FatigueTrouble thinking rememberingWaking up tired

Over the past 6 months

Pain or cramps in lower abdomenDepressionHeadache

1 Widespread Pain Index gt= 7 andSymptom Severity Score gt= 5

or Widespread Pain Index between 3-6Symptom Severity Score gt= 9

2 Symptoms have been present at a similarlevel for at least 3 months

3 Patient does not have a disorder that would otherwise explain the pain

The American College of Rheumatology 2010

Specific inflammatoryautoimmune diseases

(in particular polymyalgia rheumatica ESRuarr)

Cave misinterpretation of slightly elevated ANA or CRP

Small- Fibre- Polyneuropathy

Multiple Sclerosis

Hypothyroidism

Concept of Central Sensitization

Up-regulation of receptor activity and availability

Loss of descending inhibition

Dysregulation of dopaminergic neurotransmission within the limbic system

Genetic predisposition

Stress seems to be a strong trigger

HX of childhood maltreatment

Central sensitization implications for the diagnosis and treatment of painWoolf CJ1Author information1FM Kirby Neurobiology Center Childrens Hospital Boston Department of Neurobiology Harvard Medical School Boston MA USA cliffordwoolfchildrensharvardeduAbstract

Nociceptor inputs can trigger a prolonged but reversible increase in the excitability and synaptic efficacy of neurons in central nociceptive pathways the phenomenon of central sensitization Central sensitization manifests as pain hypersensitivity particularly dynamic tactile allodynia secondary punctate or pressure hyperalgesia aftersensations and enhanced temporal summationIt can be readily and rapidly elicited in human volunteers by diverse experimental noxious conditioning stimuli to skin muscles or viscera and in addition to producing pain hypersensitivity results in secondary changes in brain activity that can be detected by electrophysiological or imaging techniques Studies in clinical cohorts reveal changes in pain sensitivity

that have been interpreted as revealing an important contribution of central sensitization to the pain phenotype in patients with fibromyalgia

Prevalence in the general population is approximately 2

Female Male ratio 71

Most frequently diagnosed in middle aged women prevalence increases with age

Up to 40 of the pain clinic presentations

Wide spread musculoskeletal pains Muscle weakness and tenderness

muscle cramps Unexplained soft tissue swellings Hypersensitivity to touch and

temperature Tingling numbness pins and

needle sensations Disturbed temperature regulation Phono- and photo-hypersensitivity Itch without dermatological or

metabolic pathology

Symptoms are unspecific and variable in time course

Headaches Tinnitus Sleep disturbances Fatigue Poor memory and concentration Irritable bowel and bladder

syndrome Dysmenorrhia Menometrorrhagias TMJ disorder

Co-diagnosis of anxietydepressionPTSD is commonly found

Diagnosis is based on

Taking a profound history including a medicationsubstance use history

a clinical examination with specific attention to tenderness and sensory disturbances and using theACR assessment criteria 2010 plus Fibromyalgia Survey Questionnaire

Exclusion of other sinister pathology

Routine blood tests full blood counts ESR CRP CK Ca TSHRoutine testing for antibodies associated with rheumatoid diseases or lupus not recommended

Widespread Pain Index (0-19)

Pain or tenderness over the past 7 days

Shoulder R L Jaw R L

Upper arm R L Chest

Lower arm R L Abdomen

Hip R L Upper back

Upper leg R L Lower back

Lower leg R L

Symptom Severity Scale (SS scale)

0 (no problem) 1 (mild or intermittent)2 (moderate) 3 (severe)

Over the past week

FatigueTrouble thinking rememberingWaking up tired

Over the past 6 months

Pain or cramps in lower abdomenDepressionHeadache

1 Widespread Pain Index gt= 7 andSymptom Severity Score gt= 5

or Widespread Pain Index between 3-6Symptom Severity Score gt= 9

2 Symptoms have been present at a similarlevel for at least 3 months

3 Patient does not have a disorder that would otherwise explain the pain

The American College of Rheumatology 2010

Specific inflammatoryautoimmune diseases

(in particular polymyalgia rheumatica ESRuarr)

Cave misinterpretation of slightly elevated ANA or CRP

Small- Fibre- Polyneuropathy

Multiple Sclerosis

Hypothyroidism

Concept of Central Sensitization

Up-regulation of receptor activity and availability

Loss of descending inhibition

Dysregulation of dopaminergic neurotransmission within the limbic system

Genetic predisposition

Stress seems to be a strong trigger

HX of childhood maltreatment

Central sensitization implications for the diagnosis and treatment of painWoolf CJ1Author information1FM Kirby Neurobiology Center Childrens Hospital Boston Department of Neurobiology Harvard Medical School Boston MA USA cliffordwoolfchildrensharvardeduAbstract

Nociceptor inputs can trigger a prolonged but reversible increase in the excitability and synaptic efficacy of neurons in central nociceptive pathways the phenomenon of central sensitization Central sensitization manifests as pain hypersensitivity particularly dynamic tactile allodynia secondary punctate or pressure hyperalgesia aftersensations and enhanced temporal summationIt can be readily and rapidly elicited in human volunteers by diverse experimental noxious conditioning stimuli to skin muscles or viscera and in addition to producing pain hypersensitivity results in secondary changes in brain activity that can be detected by electrophysiological or imaging techniques Studies in clinical cohorts reveal changes in pain sensitivity

that have been interpreted as revealing an important contribution of central sensitization to the pain phenotype in patients with fibromyalgia

Wide spread musculoskeletal pains Muscle weakness and tenderness

muscle cramps Unexplained soft tissue swellings Hypersensitivity to touch and

temperature Tingling numbness pins and

needle sensations Disturbed temperature regulation Phono- and photo-hypersensitivity Itch without dermatological or

metabolic pathology

Symptoms are unspecific and variable in time course

Headaches Tinnitus Sleep disturbances Fatigue Poor memory and concentration Irritable bowel and bladder

syndrome Dysmenorrhia Menometrorrhagias TMJ disorder

Co-diagnosis of anxietydepressionPTSD is commonly found

Diagnosis is based on

Taking a profound history including a medicationsubstance use history

a clinical examination with specific attention to tenderness and sensory disturbances and using theACR assessment criteria 2010 plus Fibromyalgia Survey Questionnaire

Exclusion of other sinister pathology

Routine blood tests full blood counts ESR CRP CK Ca TSHRoutine testing for antibodies associated with rheumatoid diseases or lupus not recommended

Widespread Pain Index (0-19)

Pain or tenderness over the past 7 days

Shoulder R L Jaw R L

Upper arm R L Chest

Lower arm R L Abdomen

Hip R L Upper back

Upper leg R L Lower back

Lower leg R L

Symptom Severity Scale (SS scale)

0 (no problem) 1 (mild or intermittent)2 (moderate) 3 (severe)

Over the past week

FatigueTrouble thinking rememberingWaking up tired

Over the past 6 months

Pain or cramps in lower abdomenDepressionHeadache

1 Widespread Pain Index gt= 7 andSymptom Severity Score gt= 5

or Widespread Pain Index between 3-6Symptom Severity Score gt= 9

2 Symptoms have been present at a similarlevel for at least 3 months

3 Patient does not have a disorder that would otherwise explain the pain

The American College of Rheumatology 2010

Specific inflammatoryautoimmune diseases

(in particular polymyalgia rheumatica ESRuarr)

Cave misinterpretation of slightly elevated ANA or CRP

Small- Fibre- Polyneuropathy

Multiple Sclerosis

Hypothyroidism

Concept of Central Sensitization

Up-regulation of receptor activity and availability

Loss of descending inhibition

Dysregulation of dopaminergic neurotransmission within the limbic system

Genetic predisposition

Stress seems to be a strong trigger

HX of childhood maltreatment

Central sensitization implications for the diagnosis and treatment of painWoolf CJ1Author information1FM Kirby Neurobiology Center Childrens Hospital Boston Department of Neurobiology Harvard Medical School Boston MA USA cliffordwoolfchildrensharvardeduAbstract

Nociceptor inputs can trigger a prolonged but reversible increase in the excitability and synaptic efficacy of neurons in central nociceptive pathways the phenomenon of central sensitization Central sensitization manifests as pain hypersensitivity particularly dynamic tactile allodynia secondary punctate or pressure hyperalgesia aftersensations and enhanced temporal summationIt can be readily and rapidly elicited in human volunteers by diverse experimental noxious conditioning stimuli to skin muscles or viscera and in addition to producing pain hypersensitivity results in secondary changes in brain activity that can be detected by electrophysiological or imaging techniques Studies in clinical cohorts reveal changes in pain sensitivity

that have been interpreted as revealing an important contribution of central sensitization to the pain phenotype in patients with fibromyalgia

Diagnosis is based on

Taking a profound history including a medicationsubstance use history

a clinical examination with specific attention to tenderness and sensory disturbances and using theACR assessment criteria 2010 plus Fibromyalgia Survey Questionnaire

Exclusion of other sinister pathology

Routine blood tests full blood counts ESR CRP CK Ca TSHRoutine testing for antibodies associated with rheumatoid diseases or lupus not recommended

Widespread Pain Index (0-19)

Pain or tenderness over the past 7 days

Shoulder R L Jaw R L

Upper arm R L Chest

Lower arm R L Abdomen

Hip R L Upper back

Upper leg R L Lower back

Lower leg R L

Symptom Severity Scale (SS scale)

0 (no problem) 1 (mild or intermittent)2 (moderate) 3 (severe)

Over the past week

FatigueTrouble thinking rememberingWaking up tired

Over the past 6 months

Pain or cramps in lower abdomenDepressionHeadache

1 Widespread Pain Index gt= 7 andSymptom Severity Score gt= 5

or Widespread Pain Index between 3-6Symptom Severity Score gt= 9

2 Symptoms have been present at a similarlevel for at least 3 months

3 Patient does not have a disorder that would otherwise explain the pain

The American College of Rheumatology 2010

Specific inflammatoryautoimmune diseases

(in particular polymyalgia rheumatica ESRuarr)

Cave misinterpretation of slightly elevated ANA or CRP

Small- Fibre- Polyneuropathy

Multiple Sclerosis

Hypothyroidism

Concept of Central Sensitization

Up-regulation of receptor activity and availability

Loss of descending inhibition

Dysregulation of dopaminergic neurotransmission within the limbic system

Genetic predisposition

Stress seems to be a strong trigger

HX of childhood maltreatment

Central sensitization implications for the diagnosis and treatment of painWoolf CJ1Author information1FM Kirby Neurobiology Center Childrens Hospital Boston Department of Neurobiology Harvard Medical School Boston MA USA cliffordwoolfchildrensharvardeduAbstract

Nociceptor inputs can trigger a prolonged but reversible increase in the excitability and synaptic efficacy of neurons in central nociceptive pathways the phenomenon of central sensitization Central sensitization manifests as pain hypersensitivity particularly dynamic tactile allodynia secondary punctate or pressure hyperalgesia aftersensations and enhanced temporal summationIt can be readily and rapidly elicited in human volunteers by diverse experimental noxious conditioning stimuli to skin muscles or viscera and in addition to producing pain hypersensitivity results in secondary changes in brain activity that can be detected by electrophysiological or imaging techniques Studies in clinical cohorts reveal changes in pain sensitivity

that have been interpreted as revealing an important contribution of central sensitization to the pain phenotype in patients with fibromyalgia

Widespread Pain Index (0-19)

Pain or tenderness over the past 7 days

Shoulder R L Jaw R L

Upper arm R L Chest

Lower arm R L Abdomen

Hip R L Upper back

Upper leg R L Lower back

Lower leg R L

Symptom Severity Scale (SS scale)

0 (no problem) 1 (mild or intermittent)2 (moderate) 3 (severe)

Over the past week

FatigueTrouble thinking rememberingWaking up tired

Over the past 6 months

Pain or cramps in lower abdomenDepressionHeadache

1 Widespread Pain Index gt= 7 andSymptom Severity Score gt= 5

or Widespread Pain Index between 3-6Symptom Severity Score gt= 9

2 Symptoms have been present at a similarlevel for at least 3 months

3 Patient does not have a disorder that would otherwise explain the pain

The American College of Rheumatology 2010

Specific inflammatoryautoimmune diseases

(in particular polymyalgia rheumatica ESRuarr)

Cave misinterpretation of slightly elevated ANA or CRP

Small- Fibre- Polyneuropathy

Multiple Sclerosis

Hypothyroidism

Concept of Central Sensitization

Up-regulation of receptor activity and availability

Loss of descending inhibition

Dysregulation of dopaminergic neurotransmission within the limbic system

Genetic predisposition

Stress seems to be a strong trigger

HX of childhood maltreatment

Central sensitization implications for the diagnosis and treatment of painWoolf CJ1Author information1FM Kirby Neurobiology Center Childrens Hospital Boston Department of Neurobiology Harvard Medical School Boston MA USA cliffordwoolfchildrensharvardeduAbstract

Nociceptor inputs can trigger a prolonged but reversible increase in the excitability and synaptic efficacy of neurons in central nociceptive pathways the phenomenon of central sensitization Central sensitization manifests as pain hypersensitivity particularly dynamic tactile allodynia secondary punctate or pressure hyperalgesia aftersensations and enhanced temporal summationIt can be readily and rapidly elicited in human volunteers by diverse experimental noxious conditioning stimuli to skin muscles or viscera and in addition to producing pain hypersensitivity results in secondary changes in brain activity that can be detected by electrophysiological or imaging techniques Studies in clinical cohorts reveal changes in pain sensitivity

that have been interpreted as revealing an important contribution of central sensitization to the pain phenotype in patients with fibromyalgia

Symptom Severity Scale (SS scale)

0 (no problem) 1 (mild or intermittent)2 (moderate) 3 (severe)

Over the past week

FatigueTrouble thinking rememberingWaking up tired

Over the past 6 months

Pain or cramps in lower abdomenDepressionHeadache

1 Widespread Pain Index gt= 7 andSymptom Severity Score gt= 5

or Widespread Pain Index between 3-6Symptom Severity Score gt= 9

2 Symptoms have been present at a similarlevel for at least 3 months

3 Patient does not have a disorder that would otherwise explain the pain

The American College of Rheumatology 2010

Specific inflammatoryautoimmune diseases

(in particular polymyalgia rheumatica ESRuarr)

Cave misinterpretation of slightly elevated ANA or CRP

Small- Fibre- Polyneuropathy

Multiple Sclerosis

Hypothyroidism

Concept of Central Sensitization

Up-regulation of receptor activity and availability

Loss of descending inhibition

Dysregulation of dopaminergic neurotransmission within the limbic system

Genetic predisposition

Stress seems to be a strong trigger

HX of childhood maltreatment

Central sensitization implications for the diagnosis and treatment of painWoolf CJ1Author information1FM Kirby Neurobiology Center Childrens Hospital Boston Department of Neurobiology Harvard Medical School Boston MA USA cliffordwoolfchildrensharvardeduAbstract

Nociceptor inputs can trigger a prolonged but reversible increase in the excitability and synaptic efficacy of neurons in central nociceptive pathways the phenomenon of central sensitization Central sensitization manifests as pain hypersensitivity particularly dynamic tactile allodynia secondary punctate or pressure hyperalgesia aftersensations and enhanced temporal summationIt can be readily and rapidly elicited in human volunteers by diverse experimental noxious conditioning stimuli to skin muscles or viscera and in addition to producing pain hypersensitivity results in secondary changes in brain activity that can be detected by electrophysiological or imaging techniques Studies in clinical cohorts reveal changes in pain sensitivity

that have been interpreted as revealing an important contribution of central sensitization to the pain phenotype in patients with fibromyalgia

1 Widespread Pain Index gt= 7 andSymptom Severity Score gt= 5

or Widespread Pain Index between 3-6Symptom Severity Score gt= 9

2 Symptoms have been present at a similarlevel for at least 3 months

3 Patient does not have a disorder that would otherwise explain the pain

The American College of Rheumatology 2010

Specific inflammatoryautoimmune diseases

(in particular polymyalgia rheumatica ESRuarr)

Cave misinterpretation of slightly elevated ANA or CRP

Small- Fibre- Polyneuropathy

Multiple Sclerosis

Hypothyroidism

Concept of Central Sensitization

Up-regulation of receptor activity and availability

Loss of descending inhibition

Dysregulation of dopaminergic neurotransmission within the limbic system

Genetic predisposition

Stress seems to be a strong trigger

HX of childhood maltreatment

Central sensitization implications for the diagnosis and treatment of painWoolf CJ1Author information1FM Kirby Neurobiology Center Childrens Hospital Boston Department of Neurobiology Harvard Medical School Boston MA USA cliffordwoolfchildrensharvardeduAbstract

Nociceptor inputs can trigger a prolonged but reversible increase in the excitability and synaptic efficacy of neurons in central nociceptive pathways the phenomenon of central sensitization Central sensitization manifests as pain hypersensitivity particularly dynamic tactile allodynia secondary punctate or pressure hyperalgesia aftersensations and enhanced temporal summationIt can be readily and rapidly elicited in human volunteers by diverse experimental noxious conditioning stimuli to skin muscles or viscera and in addition to producing pain hypersensitivity results in secondary changes in brain activity that can be detected by electrophysiological or imaging techniques Studies in clinical cohorts reveal changes in pain sensitivity

that have been interpreted as revealing an important contribution of central sensitization to the pain phenotype in patients with fibromyalgia

Specific inflammatoryautoimmune diseases

(in particular polymyalgia rheumatica ESRuarr)

Cave misinterpretation of slightly elevated ANA or CRP

Small- Fibre- Polyneuropathy

Multiple Sclerosis

Hypothyroidism

Concept of Central Sensitization

Up-regulation of receptor activity and availability

Loss of descending inhibition

Dysregulation of dopaminergic neurotransmission within the limbic system

Genetic predisposition

Stress seems to be a strong trigger

HX of childhood maltreatment

Central sensitization implications for the diagnosis and treatment of painWoolf CJ1Author information1FM Kirby Neurobiology Center Childrens Hospital Boston Department of Neurobiology Harvard Medical School Boston MA USA cliffordwoolfchildrensharvardeduAbstract

Nociceptor inputs can trigger a prolonged but reversible increase in the excitability and synaptic efficacy of neurons in central nociceptive pathways the phenomenon of central sensitization Central sensitization manifests as pain hypersensitivity particularly dynamic tactile allodynia secondary punctate or pressure hyperalgesia aftersensations and enhanced temporal summationIt can be readily and rapidly elicited in human volunteers by diverse experimental noxious conditioning stimuli to skin muscles or viscera and in addition to producing pain hypersensitivity results in secondary changes in brain activity that can be detected by electrophysiological or imaging techniques Studies in clinical cohorts reveal changes in pain sensitivity

that have been interpreted as revealing an important contribution of central sensitization to the pain phenotype in patients with fibromyalgia

Concept of Central Sensitization

Up-regulation of receptor activity and availability

Loss of descending inhibition

Dysregulation of dopaminergic neurotransmission within the limbic system

Genetic predisposition

Stress seems to be a strong trigger

HX of childhood maltreatment

Central sensitization implications for the diagnosis and treatment of painWoolf CJ1Author information1FM Kirby Neurobiology Center Childrens Hospital Boston Department of Neurobiology Harvard Medical School Boston MA USA cliffordwoolfchildrensharvardeduAbstract

Nociceptor inputs can trigger a prolonged but reversible increase in the excitability and synaptic efficacy of neurons in central nociceptive pathways the phenomenon of central sensitization Central sensitization manifests as pain hypersensitivity particularly dynamic tactile allodynia secondary punctate or pressure hyperalgesia aftersensations and enhanced temporal summationIt can be readily and rapidly elicited in human volunteers by diverse experimental noxious conditioning stimuli to skin muscles or viscera and in addition to producing pain hypersensitivity results in secondary changes in brain activity that can be detected by electrophysiological or imaging techniques Studies in clinical cohorts reveal changes in pain sensitivity

that have been interpreted as revealing an important contribution of central sensitization to the pain phenotype in patients with fibromyalgia

Central sensitization implications for the diagnosis and treatment of painWoolf CJ1Author information1FM Kirby Neurobiology Center Childrens Hospital Boston Department of Neurobiology Harvard Medical School Boston MA USA cliffordwoolfchildrensharvardeduAbstract

Nociceptor inputs can trigger a prolonged but reversible increase in the excitability and synaptic efficacy of neurons in central nociceptive pathways the phenomenon of central sensitization Central sensitization manifests as pain hypersensitivity particularly dynamic tactile allodynia secondary punctate or pressure hyperalgesia aftersensations and enhanced temporal summationIt can be readily and rapidly elicited in human volunteers by diverse experimental noxious conditioning stimuli to skin muscles or viscera and in addition to producing pain hypersensitivity results in secondary changes in brain activity that can be detected by electrophysiological or imaging techniques Studies in clinical cohorts reveal changes in pain sensitivity

that have been interpreted as revealing an important contribution of central sensitization to the pain phenotype in patients with fibromyalgia

No curative specific treatment known

Pharmacological approaches aim at symptom control

Target is to improve patientrsquos function and subsequently quality of life by teaching self management strategies

Multidisciplinary approaches shown to be most effective

Tricyclics

SSRIs SNRIs

Up to 40 of the pain clinic presentationsAnticonvulsants(GabapentinPregabalin)

Tramadol as rescue medication

NSAIDs not recommended

Opioids are not recommended as too many significant (conterproductive) side effects in CNCP

1 A Vania Apkarian Javeria Hashmi Marwan Baliki Pain and the brain Specificity and plasticity of the brain in clinical chronic pain Pain 2010 11010

2 Clifford J Woolf Central Sensitization Implications for the diagnosis and treatment of pain Pain 32011 152 S2-15

3 Clifford J Woolf Central Sensitization - Uncovering the Relation between Pain and PlasticityAnaesthesiology 2007 Vol No 4

4 Irene Tracey and M Catherine BushnellHow Neuroimaging Studies Have Challenged Us to Rethink Is Chronic Pain a Disease

5 MC Bushnell AV Apkarian SB McMahon MKoltzenburg Representation of pain in the brain Wallrsquos and Melzackrsquos Textbook of Pain Vol 5 LondonElsevier 2006 pp107-

124

6 A Kuchinad PSchweinhardt DA Seminovicz PB Wood BA Chizh and MCBushnell Accelerated Brain Grey Matter Loss in Fibromyalgia Patients Premature Aging of the Brain The Journal of Neuroscience 4200727 (15) 4004-4007

7 Louise Oaklander Objective evidence that small- fibre polyneuropathy underlies some illnesses currently labled fibromyalgia Pain Nov 2013 Vol 154 Issue11 pp 2310-16

8 W Haueser Kati Thieme CTurk Guidelines on the management of fibromyalgia syndrome - a systematic review European Journal of Pain Jan 2010 Vol 14 p 5-10

Tricyclics

SSRIs SNRIs

Up to 40 of the pain clinic presentationsAnticonvulsants(GabapentinPregabalin)

Tramadol as rescue medication

NSAIDs not recommended

Opioids are not recommended as too many significant (conterproductive) side effects in CNCP

1 A Vania Apkarian Javeria Hashmi Marwan Baliki Pain and the brain Specificity and plasticity of the brain in clinical chronic pain Pain 2010 11010

2 Clifford J Woolf Central Sensitization Implications for the diagnosis and treatment of pain Pain 32011 152 S2-15

3 Clifford J Woolf Central Sensitization - Uncovering the Relation between Pain and PlasticityAnaesthesiology 2007 Vol No 4

4 Irene Tracey and M Catherine BushnellHow Neuroimaging Studies Have Challenged Us to Rethink Is Chronic Pain a Disease

5 MC Bushnell AV Apkarian SB McMahon MKoltzenburg Representation of pain in the brain Wallrsquos and Melzackrsquos Textbook of Pain Vol 5 LondonElsevier 2006 pp107-

124

6 A Kuchinad PSchweinhardt DA Seminovicz PB Wood BA Chizh and MCBushnell Accelerated Brain Grey Matter Loss in Fibromyalgia Patients Premature Aging of the Brain The Journal of Neuroscience 4200727 (15) 4004-4007

7 Louise Oaklander Objective evidence that small- fibre polyneuropathy underlies some illnesses currently labled fibromyalgia Pain Nov 2013 Vol 154 Issue11 pp 2310-16

8 W Haueser Kati Thieme CTurk Guidelines on the management of fibromyalgia syndrome - a systematic review European Journal of Pain Jan 2010 Vol 14 p 5-10

1 A Vania Apkarian Javeria Hashmi Marwan Baliki Pain and the brain Specificity and plasticity of the brain in clinical chronic pain Pain 2010 11010

2 Clifford J Woolf Central Sensitization Implications for the diagnosis and treatment of pain Pain 32011 152 S2-15

3 Clifford J Woolf Central Sensitization - Uncovering the Relation between Pain and PlasticityAnaesthesiology 2007 Vol No 4

4 Irene Tracey and M Catherine BushnellHow Neuroimaging Studies Have Challenged Us to Rethink Is Chronic Pain a Disease

5 MC Bushnell AV Apkarian SB McMahon MKoltzenburg Representation of pain in the brain Wallrsquos and Melzackrsquos Textbook of Pain Vol 5 LondonElsevier 2006 pp107-

124

6 A Kuchinad PSchweinhardt DA Seminovicz PB Wood BA Chizh and MCBushnell Accelerated Brain Grey Matter Loss in Fibromyalgia Patients Premature Aging of the Brain The Journal of Neuroscience 4200727 (15) 4004-4007

7 Louise Oaklander Objective evidence that small- fibre polyneuropathy underlies some illnesses currently labled fibromyalgia Pain Nov 2013 Vol 154 Issue11 pp 2310-16

8 W Haueser Kati Thieme CTurk Guidelines on the management of fibromyalgia syndrome - a systematic review European Journal of Pain Jan 2010 Vol 14 p 5-10