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Neuropathic Pain

Introduction

Neuropathic pain is pain due to a lesion, disease or pathological change in the somatosensory (nervous) system. Chronic neuropathic pain is common and may be related to: 

  • the underlying disease for which patients are referred to palliative care (eg cancer or multiple sclerosis)

  • treatment (eg post-operative neuropathic pain or chemotherapy-induced peripheral neuropathy)

  • other co-morbid conditions (eg post-herpetic neuralgia or diabetic neuropathy).

It is often complex to manage and may respond poorly to standard analgesics so specialist advice should be sought early. Neuropathic pain is commonly found in conjunction with other types of pain.

Assessment

  • Pain in a dermatomal or neuro-anatomical area, combined with a history of a disease or a lesion that might affect the nervous system, might suggest the possibility of neuropathic pain. This should be confirmed by clinical examination or detailed imaging.

  • Sensory descriptors associated with neuropathic pain include burning, tingling, pins and needles, shooting and numbness. They are not diagnostic however.

  • Confirm altered sensation in the area of pain by comparing responses with the non-painful contralateral or adjacent area of the body:

    • allodynia – painful response to light touch, eg stroking the skin with a finger or cotton wool

    • hypoaesthesia – an area of reduced sensation to non-painful or painful stimuli

    • hyperalgesia – an exaggerated pain response to stimulus, eg a lowered pin prick threshold

    • altered thermal threshold to cold or hot (eg reduced or exaggerated response to a cold metal spoon, or a hot cup of tea). 

Consider spinal cord compression.

Management

  • Opioids have some effect in neuropathic pain but many patients will need adjuvant analgesics. Corticosteroids, under specialist advice, can be used for neuropathic pain secondary to infiltrating cancer, particularly if limb weakness is present.

  • First-line adjuvants include antidepressants (eg amitriptyline) or anticonvulsants (eg gabapentin, pregabalin). Alternative 2nd line adjuvants under specialist palliative care advice include duloxetine and venlafaxine. Consider local guidance for drug choice or changing drugs, eg washout period (see Dosing guidance below.)

  • Side effects are common and include: 

    • amitriptyline – confusion, hypotension (caution should be exercised in cardiac disease).

    • gabapentin and pregabalin – sedation, tremor, confusion, peripheral oedema, dizziness (dose reduction is required in patient with renal impairment
  • Good quality evidence supports a combination of opioids and adjuvants for neuropathic pain. However, skilful titration is needed as side effects (particularly sedation and dizziness) are commonly synergistic too. In practice, this means using lower doses of both medicines than if they were used as monotherapy.
    • Allow adequate time to gradually titrate the dose of each analgesic, and advise patient, carer or both accordingly.

    • Adding lidocaine plasters or topical capsaicin cream (avoid mucous membranes) can be considered for localised pain, particularly if there is allodynia.

    • Specialists may recommend other adjuvant analgesics, eg other anticonvulsants, antidepressants, ketamine, methadone.

    • Consider referral for interventional techniques, eg radiotherapy/ transcutaneous electrical nerve stimulation (TENS)/nerve blocks/epidural or intrathecal analgesia.

      Dosing guidance; side effects are common, low dosage should be used initially particularly in the frail and elderly, use the lowest dose to achieve analgesia.

Table1

Drug

Dosing guide

Amitriptyline

10mg starting dose at night. 

If tolerated, increase to 25mgs after 3 to 7 days, then by 25mgs every 1 to 2 weeks.

Max 150mg (rarely required).

Gabapentin

Starting dose 100mg daily in elderly or frail patients, this can be increased by 100mg as is tolerated.

In fitter patients, titrate from 300mg - see BNF for further advice.

Maximum licensed dosage for neuropathic pain is 3600mg per day. Specialists may recommend higher doses.

Reduce dose in patients with renal impairment and seek specialist advice.

Pregabalin

Titrate dose from 25mg twice daily to maximum dose tolerated, not exceeding 300mg twice a day.

Reduced dose in patients with renal impairment : seek advice.

 

When switching from gabapentin to pregabalin, the following would be reasonable:

  • replace gabapentin 300mg three times a day with pregabalin 100mg twice a day

  • replace gabapentin 600mg, 900mg and 1200mg three times a day with pregabalin 200mg twice a day.

The dose of pregabalin can be further increased depending on response and tolerability to a maximum of 300mg twice a day.

Resources

Information for patients

  • Patients with chronic neuropathic pain can be encouraged to seek out self-help toolkits for non-pharmacological approaches to pain management.

  • Drugs can be used for more than their class effect, eg anti-epileptics, antidepressants.

  • Adequate analgesia may take longer in neuropathic pain.