Complex Regional Pain Syndrome Type II

Complex regional pain syndrome (CRPS) type II (formerly causalgia) is a chronic pain condition that develops after a definable injury to a major peripheral nerve, with burning pain, allodynia, hyperalgesia and sensory, autonomic, vasomotor, sudomotor, motor and trophic changes. The pain is regional and not limited to the territory of the injured nerve, and disproportionate to the initial event.

The injury may be a traumatic transection, stretch, compression, gunshot or surgical injury to the median, ulnar, sciatic, tibial or peroneal nerve, or a brachial plexus injury. It accounts for about 5 to 10% of CRPS and 2 to 14% of nerve injuries. It was described in soldiers with gunshot nerve injuries.

The Budapest criteria are used for diagnosis, with type II assigned when a nerve lesion is confirmed (clinically or by electrodiagnostic testing). Complications are chronic pain, contracture, osteoporosis, disuse, depression, sleep disturbance, disability and reduced quality of life.

Pathophysiology.

Nerve injury causes ectopic discharge from the injured axons and sprouting, with expression of adrenergic receptors on nociceptors (sympathetic afferent coupling), upregulation of sodium channels, peripheral and central sensitisation, neurogenic inflammation, and cortical reorganisation. Neuroma formation contributes. Loss of small fibres in the affected skin occurs.

Features are:

• Burning, constant pain with allodynia and hyperalgesia, beginning soon after nerve injury and spreading beyond the distribution of the nerve.
• A nerve deficit (sensory loss, weakness in the nerve territory).
• A positive Tinel sign at the site of the lesion.
• Swelling, skin temperature and colour changes, and sweating changes.
• Trophic changes (shiny skin, nail and hair changes).
• Stiffness and loss of range of motion.

Examine the nerve function in detail (motor, sensory, reflexes), Tinel sign along the nerve, skin colour, temperature, swelling, sweating, range of motion, allodynia, and trophic changes. Compare with the opposite limb.

• Clinical diagnosis by the Budapest criteria, with evidence of a nerve lesion (clinical or electrodiagnostic).
• Nerve conduction studies and electromyography at 3 to 4 weeks show the site and severity of the nerve injury and monitor recovery.
• High resolution ultrasound or MRI neurography to show neuroma, transection, compression and scar entrapment.
• Radiographs, three phase bone scan (increased uptake) and skin temperature measurement support the diagnosis; thermography and quantitative sensory testing are adjuncts.
• Exclude infection, arterial insufficiency, deep vein thrombosis, arthritis, tumour and root lesions.

Differential diagnosis.

• CRPS type I (no nerve lesion).
• Neuroma and painful neuropathy.
• Nerve entrapment and radiculopathy.
• Peripheral vascular disease, infection and arthritis.

Treatment combines management of the nerve lesion and the pain syndrome, with multidisciplinary care.

Nerve surgery. Surgery on the injured nerve may relieve pain and restore function.

• Decompression of an entrapped or compressed nerve, release of scar (neurolysis), and repair of a transected nerve (direct end-to-end repair or nerve graft within 3 to 6 months for best recovery).
• Excision of a painful neuroma with burying of the nerve end into muscle or bone, targeted muscle reinnervation, or regenerative peripheral nerve interface for amputation neuromas.
• Time the surgery in specialist units; a sympathetic block before surgery shows whether the pain is sympathetically maintained.

Rehabilitation. Graded physiotherapy and occupational therapy, desensitisation, graded motor imagery, mirror therapy, oedema control, splinting of the paralysed muscles to avoid contracture while avoiding immobilisation of the painful limb, and pain psychology.

Drug treatment.

• Gabapentin 300 mg orally at night, increased by 300 mg every 1 to 3 days to 300 to 600 mg three times daily (maximum 1800 mg daily; reduce at creatinine clearance under 60 mL/min); monitor sedation and dizziness.
• Amitriptyline 10 mg orally at night, increased by 10 mg weekly to 50 to 75 mg (maximum 75 mg daily; avoid with cardiac conduction disease, glaucoma, urinary retention or recent myocardial infarction; monitor sedation and anticholinergic effects).
• Duloxetine 30 mg orally daily for 1 week, then 60 mg daily (maximum 120 mg daily; avoid with uncontrolled hypertension, severe hepatic or renal impairment and monoamine oxidase inhibitors; monitor blood pressure and mood) is an alternative.
• Topical lidocaine 5% plaster (up to 3 plasters for 12 hours in 24) or capsaicin 8% patch for localised allodynia.
• Prednisolone 30 to 40 mg orally in the morning for 2 to 4 weeks, then tapered over 2 to 4 weeks, is used in acute warm CRPS (off label; monitor glucose, blood pressure and mood).
• Alendronate 40 mg orally once daily for 8 weeks (off label; take fasting with a full glass of water and keep upright for 30 minutes; check calcium and creatinine; avoid with eGFR under 35 mL/min/1.73 m2) in early disease with bone changes.
• Opioids are of limited value and are avoided for long term use.

Interventional treatment (specialist).

• Sympathetic blocks (stellate ganglion for the upper limb: bupivacaine 0.25% 5 to 10 mL, maximum 2 mg/kg and not exceeding 150 mg; lumbar sympathetic block for the lower limb) when sympathetically maintained pain is present.
• Peripheral nerve stimulation, spinal cord stimulation or dorsal root ganglion stimulation for refractory pain (after failure of conservative treatment for 6 months), with psychological screening and a test period.

Analgesia.

• Paracetamol 1 g orally every 6 hours as needed for up to 5 to 7 days (maximum 4 g daily; 3 g daily when weight is under 50 kg, with chronic alcohol use or hepatic impairment).
• Ibuprofen 400 mg orally every 8 hours with food for up to 5 to 7 days (maximum 1200 mg daily); avoid with eGFR under 30 mL/min/1.73 m2, peptic ulcer, heart failure or anticoagulant use.

Monitoring. Pain score, nerve function, Tinel sign advance, range of motion and mood at every visit (every 2 to 4 weeks initially). Electromyography every 3 months to follow nerve recovery. Adverse effects of gabapentin, amitriptyline, duloxetine and steroids. Skin and limb protection in an anaesthetic area. Return to work and activity goals at 3 months.

Referral and escalation. Refer every suspected CRPS type II to a pain service and a peripheral nerve surgeon early (within 4 weeks). Urgent referral for a divided nerve needing repair, an expanding haematoma, vascular compromise, infection or suicidal thoughts.

Special groups.

• Veterans and trauma patients: nerve injury from gunshot and blast injuries; early surgical exploration.
• Children and adolescents: rare; rehabilitation and psychology are the mainstay.
• Amputees: neuroma related pain needs targeted nerve procedures.
• Kidney impairment: avoid NSAIDs, reduce gabapentin, and avoid duloxetine at eGFR under 30 mL/min/1.73 m2.