Complex Regional Pain Syndrome and other pain syndromes

1. Dr Tulsi Ram Shrestha, KMCTH

2. Case
▪ A 35-year-old woman complains of diffuse burning pain in the left
arm and hand for the last 6 months.
▪ She recalls spraining her left wrist while playing volleyball.
▪ Her left hand feels colder than the right, and her fingertips are
blue.
▪ She is a recently divorced high-profile executive.

3. History
▪ 1864, Colonel Weir Mitchell
▪ Severely painful dystrophic
syndrome following ballistic injuries
in civil war soldiers: Causalgia
▪ 20th century, Peter Sudeck
▪ Features of pain, swelling, atrophy
etc. following minor injury to limbs –
hence this phenomenon came to be
called “Sudeck’s atrophy”

4. Introduction
▪CRPS describes an array of painful conditions
▪A continuing regional pain- seemingly disproportionate in
time or degree to the usual course of any known trauma
or other lesion
▪Pain- regional and usually has a distal predominance of
abnormal sensory, motor, sudomotor, vasomotor, and/or
trophic findings

5. Terminologies
▪ Allodynia Perception of an ordinarily non-noxious stimulus as pain
▪ Analgesia Absence of pain perception
▪ Anesthesia Absence of all sensation
▪ Anesthesia dolorosa Pain in an area that lacks sensation
▪ Dysesthesia Unpleasant or abnormal sensation with or without a stimulus
▪ Hypalgesia (hypoalgesia) Diminished response to noxious stimulation (eg, pinprick)
▪ Hyperalgesia Increased response to noxious stimulation
▪ Hyperesthesia Increased response to mild stimulation
▪ Hyperpathia Presence of hyperesthesia, allodynia, and hyperalgesia usually a/w overreaction, and
persistence of the sensation after the stimulus
▪ Hypesthesia (hypoesthesia) Reduced cutaneous sensation (eg, light touch, pressure, or temperature)
▪ Neuralgia Pain in the distribution of a nerve or a group of nerves
▪ Paresthesia Abnormal sensation perceived without an apparent stimulus
▪ Radiculopathy Functional abnormality of one or more nerve roots

6. IASP Diagnostic Criteria, 1994
1. an initiating event or cause of immobilization
2. continuing pain, allodynia, or hyperalgesia disproportionate to
the inciting event
3. evidence at some time(s) of edema, changes in skin blood flow,
or abnormal sudomotor activity in the painful region
4. the diagnosis is excluded by the existence of other conditions
that might account for the pain and dysfunction

7. Budapest Criteria
1. The patient has continuing pain which is disproportionate to the inciting
event
2. The patient has at least one sign in two or more categories
3. The patient reports at least one symptom in three or more categories
▪ Sensory: Allodynia and/or hyperalgesia
▪ Vasomotor: Temp asymmetry and/or skin color changes and/or skin color asymmetry
▪ Sudomotor/edema: Edema and/or sweating changes and/or sweating asymmetry
▪ Motor/trophic: Decreased ROM and/or motor dysfunction and/or trophic changes
4. No other diagnosis can better explain the signs and symptoms

8. CRPS: Types
▪ Type I
▪ corresponds to patients with CRPS without a definable nerve lesion
▪ Type II
▪ formerly termed “causalgia” and refers to cases where a definable nerve
lesion is present

9. Epidemiology
▪ Individuals aged between 61 and 70 years
▪ Female predilection (3:1)
▪ Increased preponderance for the upper limbs (3:2)
▪ Risk factors: menopause, individuals with a history of migraine,
osteoporosis, asthma and ACE inhibitor therapy and individuals
with an elevated intracast pressure due to a tight case or extreme
position
▪ Prognosis poorer in smokers

10. Incidence of CRPS
Following surgery of the upper and lower limbs Following fractures of the upper and lower limbs

11. Theories on pathophysiology of CRPS
1. CRPS arises because of an inflammatory process
2. CRPS as a sympathetically mediated condition
3. CRPS is facilitated by central sensitization
4. CRPS resultant of a ischaemia–reperfusion injury
5. Cortical reorganization and CRPS

12. Theories on pathophysiology of CRPS
6. CRPS resultant of a small-fibre neuropathy
7. CRPS as a result of sensitivity to neuropeptides
8. CRPS and psychological stress
9. Genetics and CRPS
10.CRPS as an auto-immune disorder

13. CRPS: Stages
Stage 1: warm CRPS
▪ Pain develops in a limb following an injury or spontaneously
▪ Burning throbbing aching pain, sensitivity to touch/ cold, edema
▪ Distribution of the pain: not compatible with a single peripheral
nerve, trunk, or root lesion
▪ Vasomotor disturbances: producing color/ temperature variations
▪ Radiograph of the affected limb: normal/ may show patchy
demineralization

15. Stage 2
▪ Disease progression of motor trophic changes
▪ Last 3 to 6 months
▪ Progressive soft -tissue swelling, thickening of the skin and
periarticular tissues, and muscle wasting

17. Stage 3: cold CRPS
▪ Joint contractures, limited ROM, trophic skin changes, brittle nails
▪ Severe bone demineralization on radiographic studies
▪ Independent of stage, decreased, sympathetic outflow to affected limb;
autonomic manifestations: due to catecholamine hypersensitivity→
cool, cyanotic extremity
▪ Despite decreased endogenous sympathetic mediators in the periphery,
application of exogenous catecholamines or anything triggering
increased sympathetic outflow to the periphery, like cold
temperatures→exaggerated effect and increased pain

19. DD
▪ Arthritis: atypical, Rheumatoid syndrome & Gout
▪ Peri-arthritis, septic arthritis
▪ Inflammation and infections
▪ Bursitis
▪ Capsulitis, tenosynovitis
▪ Post herpetic neuralgia
▪ Herniated disk
▪ Nerve entrapment neuropathies
▪ PVD

20. Investigations
Three-phase bone scans
▪ More sensitive investigation than plain radiography
▪ Involves use of Tc-99m-labelled bisphosphonates to detect early bone
changes
▪ Three phases: a blood pool phase, a blood phase and a scan phase
▪ Findings: increased periarticular uptake in the third phase (scan phase)
▪ Evidence of vasomotor instability and abnormal patterns of flow
distribution in the first and second phase (blood pool and blood phase)

21. Sweat testing
▪ An indicator powder that changes colour when in contact with sweat
▪ Powder applied to the affected limb, and change of colour noted
▪ Sweating is measured at rest (basal levels) and on stimulation of the
sudorimotor axonal reflex by inducing a cholinergic challenge
▪ Difference in output is measured quantitatively

22. Diagnostic sympathetic blocks
▪ Used to relieve pain by injecting LAs, or performing a sympathetic
ganglion block (e.g. stellate ganglion block for upper limb)
▪ Pain is relieved in the affected limb, but function may not be regained
▪ Placebo effect of the procedure itself should not be discounted, and it
has been shown that injection of saline into the stellate ganglion
produced pain relief similar to injection of local anaesthetic although
the effect lasted longer when local anaesthetic was injected

23. Prevention
▪ Only one prospective, double-blind study published in 1999
▪ Vitamin C was associated with a lower risk of reflex sympathetic
dystrophy after wrist fractures
▪ The study supported the use of vitamin C 500 mg daily for 50 days to
prevent the development of CRPS
Zollinger PE, Tuinebreijer WE, Kreis RW, Breederveld RS. Effect of vitamin C on frequency of reflex sympathetic dystrophy in
wrist fractures: a randomized trial. Lancet 1999; 354: 2025–8

24. Comprehensive management
▪ Patient information and education to support self-management
▪ Physical and vocational rehabilitation
▪ Pain relief- medication and procedures
▪ Psychological interventions

25. Medications and interventions
▪ Anti-neuropathic agents
▪ Gabapentin 1800 mg/day
▪ Amitriptyline 10 mg/day
▪ Pregabalin 75 mg/day
▪ 5% Lidocaine medicated plaster
▪ Bisphosphonates
▪ Inhibit bone resorption and improve levels of spontaneous pain, pressure tolerance, and joint mobility
▪ Immune-modulatory properties and though shown to be effective in CRPS

26. ▪ Ketamine
▪ NMDA receptor antagonist
▪ Topical: decrease allodynia and hyperalgesia
▪ IV : Reduce CRPS pain

27. ▪ Spinal cord stimulation
▪ Recognized treatment for neuropathic chronic pain
▪ NICE recommends SCS for patients who experience pain for ≥6 months despite conventional
medical management
▪ SCS modifies the perception of neuropathic and ischaemic pain by stimulating the dorsal
column of the spinal cord. SCS is minimally invasive and reversible.
▪ A typical SCS system has four components.
▪ Neurostimulator→ generates an electrical pulse (or receives radio frequency pulses) – this is surgically
implanted under the skin in the abdomen or in the buttock area.
▪ Electrode(s) implanted near the spinal cord either surgically or percutaneously (the latter via puncture, rather
than through an open surgical incision, of the skin).
▪ Lead→ connects the electrode(s) to the neurostimulator.
▪ Remote controller→ used to turn the neurostimulator on or off and to adjust the level of stimulation.
https://www.nice.org.uk/guidance/ta159/chapter/3-The-technology

28. ▪ Oral steroids
▪ Methylprednisolone 100 mg/day
▪ Reduced by 25 mg every 4 days

29. ▪ Bier Block
▪ Guanethedine, which acts by depleting norepinephrine in the limb
autonomic nerve endings, is supposed to reduce the regional
autonomic dysfunction.
▪ One study has demonstrated that an IVRSB with saline may be
more effective than IVRSB with guanethidine

30. Psychological interventions
▪ CBT is helpful in these patients and can even be offered to family members.
▪ Other stressors in life and potential psychiatric conditions should be
identified and dealt with by offering additional psychological support,
especially in those patients who do not make adequate progress with
treatment.
▪ CBT works in a synergistic fashion along with physical rehabilitation and
medical management of CRPS.

32. Entrapment syndrome
Nerve Entrapment Site Location of Pain
▪ Cranial nerves VII, IX, X Styloid process or stylohyoid ligament Ipsilateral tonsil, base of tongue, TM joint, and ear (Eagle syndrome)
▪ Brachial plexus Scalenus anticus muscle or a cervical rib Ulnar side of arm and forearm (scalenus anticus syndrome)
▪ Suprascapular nerve Suprascapular notch Posterior and lateral shoulder
▪ Median nerve Pronator teres muscle Proximal forearm and palmar surface of the first three digits (pronator syndrome)
▪ Median nerve Carpal tunnel Palmar surface of the first three digits (carpal tunnel syndrome)
▪ Ulnar nerve Cubital fossa (elbow) Fourth and fifth digits of the hand (cubital tunnel syndrome)
▪ Ulnar nerve Guyon’s canal (wrist) Fourth and fifth digits of the hand
▪ Lat femoral cutaneous Ant iliac spine under inguinal ligament Anterolateral thigh (meralgia paresthetica)
▪ Obturator nerve Obturator canal Upper medial thigh
▪ Saphenous nerve Subsartorial tunnel (adductor canal) Medial calf
▪ Sciatic nerve Sciatic notch Buttock and leg (piriformis syndrome)
▪ Common peroneal Fibular neck Lateral distal leg and foot
▪ Deep peroneal nerve Anterior tarsal tunnel Big toe or foot
▪ Superficial peroneal Deep fascia above the ankle Anterior ankle and dorsum of foot
▪ Posterior tibial nerve Posterior tarsal tunnel Undersurface of foot (tarsal tunnel syndrome)
▪ Interdigital nerve Deep transverse tarsal ligament Between toes and foot (Morton neuroma)

33. Myofascial pain syndromes
▪ Aching muscle pain, muscle spasm, stiffness, weakness, autonomic dysfunction
▪ Trigger points: discrete areas of marked tenderness in one or more muscles or the associated
connective tissue
▪ Signs of autonomic dysfunction (vasoconstriction or piloerection)
▪ Pain characteristically radiates in a fixed pattern that does not follow dermatomes.
▪ Gross trauma or repetitive microtrauma: major role
▪ Levator scapulae, masseter, quadratus lumborum, gluteus medius
Management
▪ May spontaneously resolve without sequelae, many patients continue to have latent trigger
points
▪ When trigger points are active, treatment is directed at regaining muscle length and elasticity
▪ Analgesia and Physical therapy

34. Fibromyalgia syndrome
▪ Chronic disorder- widespread and persistent non-inflammatory
musculoskeletal pain
▪ Concomitant symptoms: fatigue, insomnia, morning stiffness, depression,
anxiety, cognitive problems (concentration difficulties, memory/attention
problems)
Criteria
▪ WPI score ≥ 7, and SS scale score ≥ 5, or WPI of 3 to 6 and SS scale score ≥ 9
▪ Symptoms present at a similar level for at least 3 months
▪ Absence of another disorder that would otherwise explain the pain
Management
▪ Cardiovascular conditioning, strength training, improving sleep hygiene,
cognitive–behavioral therapy, patient education
▪ Pharmacotherapy- Pregabalin, duloxetine

35. Low back pain
▪ Paravertebral Muscle & Lumbosacral Joint Sprain/Strain
▪ Buttock Pain
▪ Degenerative Disc Disease
▪ Prolapsed Intervertebral Disc
▪ Spinal Stenosis
▪ Congenital Abnormalities
▪ Tumors
▪ Infection

36. Neuropathic pain
Diabetic Neuropathy
▪ Pathophysiology: Microangiopathy and to abnormal activation of glycation of
proteins
▪ M/c: Peripheral polyneuropathy
▪ symmetric numbness
▪ stocking-&-glove distribution
▪ paresthesias
▪ dysesthesias, pain
▪ Loss of proprioception→ gait disturbances
▪ Sensory deficits→ repetitive traumatic injuries
Management
▪ Symptomatic, glucose control
▪ Combination of an antiepileptic drug and a tricyclic antidepressant may be effective.

37. Post herpetic neuralgia
▪ Severe, radicular pain following resolution of
acute herpes zoster
▪ Typically affects the V1 nerve
▪ Trophic changes: scarring, loss of pigmentation/
hair, allodynia
▪ Paroxysmal bouts of pain during day,
superimposed on burning pain or dysaesthesia
Management
▪ Analgesics, Steroids
▪ Sympathetic blocks
▪ Antidepressants

38. Headaches

39. Trigeminal neuralgia
▪ tic douloureux, prosopalgia,Fothergill's disease, suicide disease
▪ Classically UL, usually located in the V2 or V3 distribution
▪ Electric shock quality, with episodes lasting from sec to min
▪ Often provoked by contact with a discrete trigger
▪ Facial muscle spasm
Common causes
▪ Compression by superior cerebellar artery as it exits brainstem
▪ Multiple sclerosis
▪ Cerebellopontine angle tumor
Management
▪ Carbamazepine (risk of agranulocytosis), Phenytoin or baclofen may be added
▪ Invasive treatments→ glycerol injection, radiofrequency ablation, balloon compression of
the gasserian ganglion, and microvascular decompression of the trigeminal nerve.