• Consider whether there is a treatable underlying cause (for example, nerve compression from bone metastases or soft-tissue disease) and seek specialist advice regarding further treatment of the cause (for example, surgical stabilization for bone metastases or radiotherapy for soft-tissue disease).
• If pain is purely neuropathic and reversible conditions (for example, vitamin B₁₂ deficiency) have been excluded:
• Consider offering amitriptyline (off-label use) or pregabalin (or gabapentin if there is a local decision to prefer gabapentin over pregabalin).
• Titrate the dosage according to response and tolerability.
• For further information, on contraindications, cautions, managing adverse effects, and second-line options if amitriptyline or pregabalin are not effective, see the CKS topic on Neuropathic pain - drug treatment.
• If pain is of mixed origin, use standard analgesics in addition to a tricyclic antidepressant or pregabalin (or gabapentin) if pain is not adequately controlled with standard analgesia alone. See Non-emergency management of persistent pain.
• Seek specialist advice or consider referral if pain persists.

Treating the underlying cause of neuropathic pain

• The recommendation to manage any treatable causes of neuropathic pain is based on a textbook on symptom relief in palliative care [Regnard and Hockley, 2004a], a chapter from the ABC of palliative care [Colvin et al, 2006], a textbook of symptom management in advanced cancer [Twycross and Wilcock, 2001], and the Palliative Care Formulary [Twycross and Wilcock, 2007].

Management of neuropathic pain

• If pain is purely neuropathic and reversible conditions (for example, vitamin B₁₂ deficiency) have been excluded, CKS recommends that neuropathic pain should be managed in accordance with guidance issued by National Institute for Health and Clinical Excellence (NICE) on drug treatment of neuropathic pain in adults in non-specialist settings [NICE, 2010]. For further information, see the CKS topic on Neuropathic pain - drug treatment.
• Having reviewed the evidence for a number of neuropathic conditions (including cancer pain and neuropathic cancer pain), the NICE guidance development group (GDG) treated the term 'neuropathic pain' as a blanket condition regardless of the underlying cause; the GDG considered this to be helpful and practical for non-specialist healthcare professionals and patients. However, condition-specific recommendations were made if robust evidence on clinical efficacy and cost-effectiveness existed (as in the case of painful diabetic neuropathy), or where the evidence was clearly uncertain and insufficient to alter current clinical practice (as in the case of trigeminal neuralgia). The GDG acknowledged that evidence for treating a particular neuropathic pain condition with a particular aetiology is often extrapolated to other neuropathic pain conditions with other aetiologies, although there is little evidence to support the validity of this [NICE, 2010].

Persistent neuropathic pain

• CKS recommends seeking specialist advice for people with persistent neuropathic pain because various additional treatments may be considered for use by specialists, including cognitive behaviour therapy, ketamine, methadone, nerve blocks, or spinal analgesia.