Brains In Pain

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Brains In Pain

• Dr.Helen Cohen
• Honorary Consultant / Arc Clinical Research
  Fellow
• RNHRD

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Overview

• CRPS Current views
• My research investigating allodynia
• CRPS What does the patient tell us?
• Symptoms/signs as organic phenomena
• Referred sensations
• Visual disturbances
• Parietal lobe

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Complex Regional Pain Syndrome
Pseudonyms

• Reflex Sympathetic Dystrophy RSD
• Algodystrophy
• Sudecks Atrophy
• Causalgia
• Shoulder-Hand syndrome

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Types

• Type 1 No nerve injury
• Type 2 Nerve injury
• No difference in presentation

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Bruehl
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CRPS
Swelling Sweating Colour Temperature Allodynia
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Thermography
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Definition

• IASP definition of CRPS
• Condition initiated by an injury (NOT always)
• Not limited to distribution of single
  peripheral nerve
• Pain disproportionate to inciting event
• Associated at some point with
• oedema
• changes in skin, blood flow
• abnormal sweating
• or allodynia
• or hyperalgesia
• Site usually distal extremity

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Diagnostic Criteria
IASP 2003

• Continuing (spontaneous and/or evoked) regional
  pain that is seemingly disproportionate in time
  or degree to the usual course of any known trauma
  or other lesion
• At least one symptom in 3 or more of the
  following categories
• At least one sign in 2 or more of the following
  categories
• Positive Sensory
• allodynia, hyperalgesia, deep somatic allodynia
• Vascular
• colour or temperature changes/asymmetry
• Sweating abnormalities or oedema
• Motor/Trophic
• weakness, ? ROM, skin/nail/hair changes, tremor,
  dystonia
• Research criteria at least one symptom in each
  category, and one sign in 2 or more catagories

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Typical CRPS literature

• Sympathetic dependent / independent pain
• Stages Hot / hot cold / cold
• Rare
• Cured by sympathetic blocks, sympathectomies,
  local guanethidine infusions etc

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Possible mechanisms

• Sensitised pain nerves CNS
• Neurogenic inflammation
• Autonomic sympathetic nerve involvement
• Abnormal nerve firing
• Motor system changes due to abnormalities in
  discharge patterns of a and ? motor neurons
• Genetic predisposition
• Other mechanisms such as exaggerated inflammatory
  response or protective disuse or myofascial
  dysfunctions

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Epidemiology

• Incidence of CRPS type 1 2 1 to 15.(1)
• Incidence of CRPS type 1 is 1-2 after various
  fractures.
• In prospective studies of Colles fracture the
  incidence is 7-35.
• Approx. 5 of these patients have lasting
  problems.
• Chronic, severe CRPS was rarer (lt2).
• 2-5 may develop CRPS type 2 after peripheral
  nerve injury.
• Ratio of female male is 31.(2)
• The affected age group is between 18 and 71 years
  with a mean age of 41.8 years.(3)
• CRPS can also occur in children. Children with
  diabetes have a higher incidence of CRPS as
  compared to non-diabetic children.(4)

(1) Purdy CA and Miller SJ. Reflex sympathetic
dystrophy syndrome. Comprehensive textbook of
foot surgery. (2nd ed), 1124-1134. 1992.
Williams and Wilkins. (2) Veldman PHJM, Reynen
HM, Arntz IE, and Goris RJA. Signs and symptoms
of reflex sympathetic dystrophy. Lancet 342,
1012-1016. 1993. (3) Allen G, Galer BS, and
Schwartz L. Epidemiology of complex regional pain
syndrome a retrospective chart review of 134
patients. Pain 80(3), 539-544. 1999. (4)
Schiller JE. Reflex sympathetic dystrophy of the
foot and ankle in children and adolescents.
Journal of the American Podiatry Medical
Association 79(11), 545-550. 1989.
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Presentation

• Severe, unremitting pain non-dermatomal
• Vasomotor / sudomotor disturbance
• Cast too tight
• Oedema trophic changes
• Allodynia
• Guarding
• Neuropathic quality to pain
• Lack of effect of analgesics inc. opiates

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Investigations

• Often not very helpful
• Xray osteoporosis
• Isotope bone scan Classic findings include
  increased periarticular uptake throughout the 3
  phases (blood pool, blood phase, scan phase)
• However, in some patients a reverse or mixed
  pattern is seen

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Investigations

• MRI A variety of MRI features have been reported
  including skin thickening, oedema, synovial
  hypertrophy, joint effusions and bone marrow
  oedema
• Thermography
• Sympathetic function
• EXCLUDE any other causes

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Pharmacological Management of CRPS

• OR
• Why dont drugs seem to work?

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CRPS Treatments

• Whats the evidence ?
• Very little
• 2 Reviews
• Local anesthetic sympathetic blockade for complex
  regional pain syndrome MS Cepeda, DB Carr, J Lau
  2005
• 2 randomised clinical trials, 23 pts
• Sympathectomy for neuropathic pain
  A Mailis-Gagnon and A Furlan 2002
• 4 studies

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Why dont drugs seem to work?

• Causes of CRPS largely unknown
• It is suggested that
• Multiple mechanisms involving various regions
  of entire neuraxis underlie the development of
  CRPS
• Pathophysiology may vary from one patient to
  another

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Too many targets

• Network dysfunction other factors
• NO magic bullet
• Often opiate resistant

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Approaches to the drug treatment of CRPS

• Standard WHO pain ladder

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World Health Organization Pain Ladder
Freedom from cancer pain
Opioid for moderate to severe pain / -
Non-opioid / - Adjuvant
Morphine Paracetamol NSAID
3
Pain persisting or increasing
Opioid for mild to moderate pain / -
Non-opioid / - Adjuvant
Codeine Paracetamol NSAID
2
Pain persisting or increasing
Non-opioid / - Adjuvant
1
Paracetamol NSAID
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Individualised Approach

• Symptom based
• Systems based

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Analgesics

• Start with WHO
• KEEP IT SIMPLE (if drugs dont work, dont give
  em)
• If peaks troughs in pain control
• Consider slow release preparations
• If opioids are helping
• Consider transdermal patches - matrix patch
  (buprenorphine, fentanyl)
• Keeping patch on change over nausea titration
  up down heat drug release

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Opioids

• If they dont help, STOP them!
• Dont keep increasing dose will not help
• Opioid doped patients dont rehab!
• Some patients will be keen to come off others
  wont let the crutch go.

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Adjuvant Medications

• NSAIDS
• COX I / COX II
• Slight increased risk of stroke heart
  attack
• True for any NSAID ?
• GI ulceration
• Risk / benefit analysis

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Neuromodulatory

• Anticonvulsant medications
• Gabapentin, Pregabalin, Carbamazepine, Phenytoin,
  Topiramate, Valproate etc
• Side effects drowsiness, weight gain

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Antidepressants

• Tricyclics (nortriptyline, amitriptyline)
• SSRI (fluoxetine), SNRI (venlafaxine), NARI
  (reboxetine)
• Useful for BOTH pain and anxiety / depression
  related problems
• Different dosages for pain
• May help with poor sleep pattern
• Give nor/amitriptyline at 8 pm

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Muscle relaxants

• Muscle spasm dystonia in CRPS
• Baclofen
• SE sedation, hypotonia
• Benzodiazepines
• SE habituation, drowsiness

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NMDA receptor antagonists

• Ketamine
• Ketamine coma

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Calcium modulating

• Calcitonin nasal, s/c
• Pamidronate infusion

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Immunomodulatory

• Anti-TNF
• IV-immunoglobulins
• Steroids

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Interventional

• Nerve / sympathetic blocks
• Local eg.stellate ganglion
• Regional use of cuff
• Agents lignocaine, clonidine, baclofen,
  guanethidine
• Sympathectomy chemical, surgical
• (risk of abnormal sweating, increased pain)
• Spinal column stimulator
• Intrathecal drugs baclofen, clonidine, opioids
• Amputation

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Sympathectomy

• Cochrane review Authors' conclusions
• The practice of surgical and chemical
  sympathectomy is based on poor quality evidence,
  uncontrolled studies and personal experience.
  Furthermore, complications of the procedure may
  be significant, in terms of both worsening the
  pain or producing a new pain syndrome and
  abnormal forms of sweating (compensatory
  hyperhidrosis and pathological gustatory
  sweating).

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Non-Pharmaceutical

• Occupational therapy
• Desensitisation techniques
• Physiotherapy, hydrotherapy
• Mirror Visual Feedback
• Graded Motor Imagery
• Pain management
• Clinical psychology

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Key Points

• Opiates may not work
• Keep drug treatment simple
• There is very little evidence for the beneficial
  effect of most treatments for CRPS
• Non-drug treatments are a powerful, underused tool

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My Research
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Background knowledge
Cortical reorganisation in CRPS Confirmed by
imaging studies Reverses with resolution of
disease (Flor)
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Conflicting sensory information

• May cause pain (Harris)
• Cortical reorganisation as a cause
• Can cause pain in healthy volunteers
• Can worsen pain in FMS

Allocentric/egocentric integration
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Allodynia

• When a normally non-noxious stimulus is perceived
  as noxious ie. painful

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ARC Grant Work

• Allodynia in CRPS, RA, OA
• Autonomic dysfunction in CRPS
• Allocentric/egocentic mismatch susceptibility
• Correlation of the above
• Guide treatment approach

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Methods
The problem of qualia (is what I call green the
same as what you see as green?) QST Semmes
Weinstein monofilaments for mechanical detection
thresholds
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QST gadgets
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Body Map
MDT thresholds (grams) Allodynia Paraesthesia Refe
rred sensations
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Laser Doppler Flowmetry
CRPS
Healthy
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What does the patient tell us ?

• Foreigness of the limb
• Dislike/hatred of the limb
• Hiding/neglecting the limb
• Distorted body image
• Touch sensitivity beyond the limb
• Clumsiness/lack of control
• Visual disturbance
• Language/numerical problems
• Sensitivity to other sensory modalities
• Protective zone

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Bizarre symptoms as organic phenomena

• Chronic pain as a network dysfunction
• No single pain centre
• Somatotopic maps S1,S2, beyond
• Many brain areas can be activated
  (fMRIconsistently spinal cord, thalamus, S1, S2,
  insula, anterior cingulate and prefrontal cortex
  ALSO hippocampus, posterior parietal lobe, basal
  ganglia and brainstem)

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Referred sensations
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FACE BESIDE HANDS
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CRPS

• Expansion of receptive fields in somatosensory
  cortex.Cortical reorganization

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Visual Pathways
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Dorsal / ventral pathways
Old / unconscious / where
New / conscious / what
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Conflicting visual information
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What happens in CRPS ?

• Disturbed pain matrix
• Add visual incongruence
• Result PAIN

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Duck / rabbit
Conscious object recognition Memory
dependent Top-down bias
Ventral pathway
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Necker cube
Perspective, depth, scaling rules Object
recognition Bottom up bias
Dorsal pathway
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CRPS visual disturbances

• Movement of stable objects
• Dorsal pathway network dysfunction ( parietal
  lobe)
• Asymmetric autonomic sympathetic responses to
  AVS independent of baseline function

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Parietal lobe function

• Left sensory integrative processing important
  for normal language and maths
• Right sensory integrative processing related
  to the use of spatial information in
  perceptual, cognitive motor behaviours

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Parietal Lobe

• Left sided lesions
• Conduction aphasia
• Tactile agnosia
• Dysphasia
• R-L disorientation
• Finger agnosia
• Agraphia
• Body image disorders
• Sensory extinction
• Astereognosis
• Alexia
• Dysgraphaesthesia

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Right sided lesions

• Anosognosia (lack of awareness of disease)
• Neglect
• Tactile agnosia
• Asomatognosia
• Constructional dyspraxia

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Parietal Dysfunction?

• In CRPS patients there may be
• Neglect like phenomena
• Body dysmophia
• Motor dyspraxias
• Unusual sensory patterns extinction, allochiria
• Parietal abnormalities on formal detailed bed
  side testing

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CRPS

• Distorted body image
• Expanded peripersonal space
• Feel touch above body surface

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Phantom Limb
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Organic basis for the Bizarre

• Severe allodynia breeze is painful
• Cortical reorganisation referred sensations,
  phantom limb-like sensations
• Sensory conflict as basis for pain
• Chronic pain sensitised system (peripheral
  central) lowered thresholds
• Brain network dysfunction eg. Parietal
  dysfunction
• Role of psychological distress in chronic severe
  pain

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Translation of research into clinical practice

• Understanding of chronic pain mechanisms
• Which ones are more dominant in this patient?
• Individualise treatment
• Allodynia in chronic pain conditions
  (eg.fibromyalgia) translation of understanding
  treatment techniques

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The pain personality

• Brain network dysfunction
• What if there were similar dysfunctional cortical
  networks in chronic pain.
• A common personality might emerge

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Acknowledgements

• Funding Bodies Other Partners
• Arthritis Research Campaign
• Gwen Bush Foundation
• RSD-UK
• Royal National Hospital for Rheumatic Diseases
  Donated Funds

• CRPS Clinical Research Team
• Professor David Blake
• Dr. Helen Cohen
• Mrs Carole Dyer
• Dr. Jane Hall
• Dr. Nigel Harris
• Ms Keri Johnson
• Ms. Jenny Lewis
• Dr. Karen Rodham