Neuropathic Pain

Introduction

Neuropathic pain is pain caused by injury or disease of the peripheral or central nervous system. Sometimes colloquially called “nerve irritation pain”. It is one of the major causes of chronic pain.

It is thought to affect between 1-8% of the population.

Management firstly should involve treatment of the underlying condition, but in many cases, neuropathic pain becomes chronic. In these cases, management involves a variety of drugs, usually from the various classes of antidepressants, which are thought to also affect peripheral nerve signal transmission, in addition to their antidepressant effects.

• In many cases, prescribing is not in line with best evidence and doctors must take care to use appropriately evidenced treatments

Epidemiology

• Estimates of prevalence vary between studies from 1-8%
• Diabetic neuropathy affects 15-25% of diabetic patients
• Postherpetic neuralgia occurs in:
  • 10-20% of patients at one month from onset of rash
  • 5-10% at 3 months from onset of rash

Aetiology

There are many possible causes of neuropathic pain. These include:

• Diabetic peripheral neuropathy
• Spinal cord injury
• Complex regional pain syndrome
• Trigeminal neuralgia
• Post-hermetic neuralgia
• Alcoholic neuropathy
• Phantom limb pain
• Tumour – particularly of the brachial or lumbar sacral plexus
• Post surgical
• Other neuralgias

Presentation

Pain is typically described as “burning”, “aching” or “shooting”. Can be continuous or intermittent, generally is continuous with some day to day variation, and specific actions that may cause worsening of the pain. Other features include:

• Hyperalgesia – pain out of proportional to a normal painful stimulus
• Allodynia – pain caused by typically non-painful stimulus
• Parasthesia – pins and needles types sensation

Management

Management is very similar to others causes of chronic pain.

If possible, treat the underlying disorder, or at the very lest, attempt to limit its progression (e.g. in diabetes).

Analgeisa

Analgesic therapy typically would involve the analgesic ladder:

• Paracetamol, plus
• NSAIDs, plus
• Neuropathic pain agents (see below)

The role of opiates remains somewhat controversial. Most studies conclude that they are of very limited use in chronic pain and their use should be discouraged.

Many agents have been proven effective for neuropathic pain. These include:

• Tricyclic antidepressants
  • Amitriptyline – e.g. 10-25mg at night, increasing every 70-10 days to 100mg max
  • Nortriptyline
  • Antidepressants reduce pain independently of their antidepressant effects. It is believed to be through their action on noradrenaline and serotonin uptake, although they are also known to have local anaesthetic activity
  • Doses are typically smaller than those use to treat depression
  • Trials suggest 1 in 3patients benefit from TCAs
  • BEWARE of serotonin syndrome in anyone taking more than one drug known to affect serotonin uptake – this includes almost all types of antidepressants as well as tramadol (a synthetic opiate with serotonin effects)
• SNRI
  • Selective noradrenaline and serotonin re-uptake inhibitors
  • Duloxetine – particularly useful for peripheral diabetic neuropathy
  • Generally less effective than tricyclics for this indication
  • Trials suggest 1 in 5 patients benefit from an SNRI
• SSRI
  • Selective serotonin re-uptake inhibitors
  • Generally less effective than SNRIs for this indication
  • Trials suggest 1 in 7 patients benefit from an SSRI
• Antiepileptics
  • Thought to work by increasing the activity and / or effectiveness of GABA – which is typically involved in inhibitory actions in the brain and spinal cord
  • Gabapentin and pregabalin – the mechanisms are not fully understood, but thought to act on voltage-gated ion channels and affect the release of substance p, noradrenaline and glutamate.
    • Particularly useful in diabetic neuropathy and post-herpetic neuralgia
    • Gabapentin improves pain in about 1 in 7 patients
    • Pregabalin improves pain in about 1 in 5 patients
    • Both can lead to dependence and should be used with caution
    • Gabapentin is considered more effective and should be used in preference to pregabalin
  • Other anti-epileptics (such as sodium valproate, phenytoin, carbamazepine and lamotrigine) have NOT been proven to be effective. Some guidelines (such as SIGN  – Scottish guidelines) have recommended carbamazepine but evidence is very limited

Which agent to use?

Guidelines vary on which agents to use (which seems to suggest the evidence fOr the efficacy of one agent over another is poor [author’s opinion]).

UK NICE guidelines ??

• Start with any of:
  • Amitriptyline
  • Gabapentin
  • Pregabalin
  • Duloxetine
• Swap to an alternative if not effective
• Consider combinations to increase effectiveness – but there is no particular evidence to suggest one combination is better than any other
• Consider tramadol short term as an ‘acute rescue’ therapy
• Consider capsaicin cream
• [Author’s opinion] – I would avoid using amitriptyline and duloxetine in combination due to risk of serotonin syndrome, and gabapentin and pregabalin in combination because of their similar mechanism of action

Australian eTG guidelines ??

• 1st line
  • Amitriptyline – 10-25mg PO nocte
  • Increase every 7 days to a maximum of 100mg nocte
• 2nd line
  • Gabapentin – 100-300mg PO daily, increase every 3 days up to 2400mg daily, OR
  • Pregabalin – 75mg PO daily, increase to BD after 2-3 days and then up to a maximum of 300mg BD, OR
  • Duloxetine – 30mg PO daily, increasing to 60mg daily after 1 week and then a maximum of 60mg BD

In general, the use of opioids should be avoided and discouraged, although in reality, as all chronic pain starts out as acute pain, many patients you meet maybe on long term opioids. (Seems to be more of a problem in Australia than in the UK in the author’s experience).

• Tramadol usually recommended as the first line opioid if one is to be trialled
• Generally evidence for opioids in acute pain is good, but for chronic pain is very poor. Tolerance and dependence (addiction) developed quickly and can be hard to treat
• Misuse of prescribed opiates is common
• Attempt to “de-prescribe” at every opportunity

In a specialist (pain clinic) setting, some of the other agents may be tried:

• Cannabis extract
• Capsaicin patch
• Lamotrigine
• Leviteracetam (Keppra)
• Topiramate
• Venlafaxine
• Ketamine infusion (in an inpatient setting)

Non-pharmacological treatments

Cognitive behavioural therapy

• There is an association between chronic pain and depression. It has also been shown that even in cases without diagnosed depression, cognitive behavioural therapy may improve chronic pain (modestly).
• This can be a difficult conversation to have with a patient, although many patients just want their pain to get better and are open to many methods of how to do this

PENS

• Percutaneous electrical nerve stimulation may provide some short term analgesic effects
• TENS – transcutaneous electrical nerve stimulation has NOT been shown to be effective

Other measures

There is no proven evidence for the benefit of any of the following:

• Acupuncture
• Homeopathy
• TENS

Trigeminal neuralgia is a special case and considered separately.

• Carbamazepine and /or phenytoin may be used and are often effective

References

• Neuropathic Pain – patient.info
• Neuropathic pain: Treatment – eTG
• Murtagh’s General Practice. 6th Ed. (2015) John Murtagh, Jill Rosenblatt
• Oxford Handbook of General Practice. 3rd Ed. (2010) Simon, C., Everitt, H., van Drop, F.
• Beers, MH., Porter RS., Jones, TV., Kaplan JL., Berkwits, M. The Merck Manual of Diagnosis and Therapy

Read more about our sources

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