Neuropathic Pain and its Management

Neuropathic pain is defined by the International Association for the Study of Pain (IASP) as pain arising from inflammation or injury to the peripheral or central nervous system, or from dysfunction of the nervous system.¹
The terminology becomes a little confused, because the term 'neuropathic pain' was previously confined to peripheral nerve pain only. It is now used for pain of central origin as well (e.g.lateral medullary syndrome), and the addition of the concept of dysfunction allows for the inclusion of reflex sympathetic dystrophy.

The term 'neurogenic pain' was proposed to embrace both peripheral and central causes. However, at a meeting of the IASP in 2007 it was proposed to delete the term peripheral neurogenic pain, and introduce the term nociception, which the IASP define as the neural processes of encoding and processing noxious stimuli. This differentiates nociception (an unconscious reaction of the nervous system to tissue damage) from pain (a conscious sensation).²

• The discomfort is usually of a chronic nature and may be described by the patient as a burning sensation, a sharp, stabbing or shooting pain, or 'like an electric shock'.
• Other features may include:
  • Allodynia - seemingly harmless stimuli such as light touch can provoke pain.
  • Hyperpathia - a short episode of discomfort causes prolonged severe pain.
  • Hyperalgesia - discomfort which would otherwise be mild is felt as severe pain. The IASP state that hyperalgesia is a psychophysical term, it is has been suggested as the umbrella term for all conditions of increased pain sensitivity. Its definition parallels that of the physiological term "sensitisation".³

• One study suggests that approximately 8% of the UK population suffer from neuropathic pain.⁴
• This is consistent with a rather more selective group of patients attending a Neurology Clinic in Spain. Of the 1,972 patients attending, 7.95% were diagnosed as having neuropathic pain.⁵
• A study carried out in UK general practice found that the incidence of phantom limb pain and post-herpetic neuralgia are decreasing whilst painful diabetic neuropathy plateaued and trigeminal neuralgia remained constant.⁶

Aetiology^1,7

• The treatment of the underlying causative condition is central to the management of neuropathic pain but is outside the scope of this record. Neuropathy caused by mechanical pressure for example may require surgical and other interventional procedures.
• The main role of the GP in the management of neuropathic pain is in the control of symptoms where the underlying cause is medical, where the condition is of a chronic, recurring or acute self-limiting nature, or whilst awaiting specialist intervention.

Non-pharmacological measures

• Psychological techniques - there are no meta-analyses in the management of neuropathic pain per se, but CBT performed well in patients who had chronic pain from various causes.¹³ The trials that have been done indicate that CBT and other psychological techniques may be helpful in some forms of neuropathic pain.^14,15 Studies of chronic pain management suggest that a combination of psychological, pharmacological and physical therapies, tailored to the needs of the individual patient, may be the best approach.¹⁶
• Patient education - this is often quoted as a strategy, though the evidence-base is lacking.¹⁷ Logic would dictate however that an informed patient is more able to be involved in decisions about their care, and this is certainly relevant in terms of compliance.¹⁸
• Electrical stimulation - interpretation of systematic trials are difficult due to differing methodologies.¹⁹ However, transcutaneous electrical nerve stimulation (TENS) performs consistently well compared to placebo.^20,21
• Acupuncture - systematic evidence to support its use in neuropathic pain is lacking.²² There is some evidence that percutaneous nerve stimulation (PENS), which combines the techniques of acupuncture and TENS, may be helpful for some patients with diabetic neuropathy.²³

Pharmacological measures

Most controlled trials have focussed on the relief of pain, rather than the sometimes more distressing symptoms of allodynia or hyperalgesia, or the effect of treatment on the quality of life.²⁴ This makes a comparative interpretation of the available treatments difficult.^25,26The general consensus, however, supports the use of the following drugs:^27,28

• Non-opioid analgesics and NSAIDs These perform well against placebo, particularly in diabetic neuropathy, but most patients require more targeted treatments.^29,30
• Antidepressants A Cochrane review found that the 'numbers needed to treat' (NNT) for tricyclic antidepressants (TCAs) and venlafaxine was three.³¹ In other words, of every three patients prescribed these drugs, one would obtain at least moderate relief from neuropathic pain. Amitriptyline is the most frequently prescribed TCA (unlicensed use), initially 10-25 mg nocte. The dose may be increased gradually to 75 mg daily if required. Higher doses should be instituted under specialist supervision .A systematic review showed no difference between the tricyclics regarding effectiveness, but nortriptyline, also given initially at 10-25 mg at night, may cause less side effects.³² There is limited evidence that SSRIs are effective.³¹
• Anti-convulsants Both gabapentin and pregabalin are licensed for the treatment of neuropathic pain.^33,34 The optimum dose of gabapentin for this indication would seem to be 1800-3600 mg daily.³³ and of pregabalin 100-600 mg daily.³⁴ A Cochrane review supported the use of gabapentin in chronic neuropathic pain, but was inconclusive about its role in acute pain.³⁵ A recent trial supported the use of pregabalin in central neuropathic pain.³⁶ Both drugs can cause dizziness, drowsiness, and peripheral oedema. However, trials suggest that pregabalin is effective at lower doses, and therefore has less potential than gabapentin for causing adverse effects at a symptom-controlling dose.³⁷
• Opioids These may produce only a partial response, but may be useful where other methods fail. There is systematic evidence to support the use of tramadol,³⁸ and oxycodone.³⁹ There are small randomised trials supporting the use of methadone, but larger systematic reviews are required.⁴⁰ A Cochrane review found that whilst short-term trials were contradictory, intermediate-term trials provided evidence of effectiveness. It concluded that longer-term trials were required.⁴¹
• Topical creams Capsaicin cream is licensed for neuropathic pain. It can be applied three to four times a day. It should not be used on broken or inflamed skin. It can cause irritation at the site of application.^42,43 Systematic review suggests it may be useful as an adjunct for a small number of patients unresponsive to other treatment.⁴⁴
• Cannabinoids Research suggests that these may well prove useful treatment options in the future.⁴⁵
• Specialist-instituted treatments These include lidocaine^42,46 and ketamine, both of which are given intravenously (unlicensed use).⁴⁷ Sodium valproate and phenytoin are now generally reserved for specialist use,⁴⁸ and corticosteroids are sometimes given to relieve pressure in compression neuropathy.⁴² Intrathecal injections and nerve blocking techniques are other options, but relief tends to be temporary.⁴⁹

Referral to a specialist in pain management

This should be considered whenever there is doubt about the diagnosis of neuropathic pain, if there has been inadequate response to treatment, or if other treatments not available in primary care are required (e.g. unlicensed drugs, physical therapy such as nerve blocks, etc).