Neuritic (Neuropathic) Pain

Neuritic (Neuropathic) Pain Definition and classification

Neuropathic pain is pain caused by a lesion or disease of the somatosensory nervous system, at either a peripheral or a central level.

It is a clinical description, not a diagnosis — the definition requires a demonstrable lesion or disease that satisfies standard neurological criteria.

Contrast with nociceptive pain (activation of receptors in the peripheral somatosensory nervous system by mechanical, thermal or chemical stimuli in non-neural tissue — soft-tissue, musculoskeletal and visceral pain) and with nociplastic pain (altered nociception without clear tissue damage or a somatosensory lesion — fibromyalgia, non-specific low back pain, irritable bowel syndrome, complex regional pain syndrome type 1). "Nociplastic" replaces the older terms dysfunctional pain, central sensitization and pain of unknown origin.

Peripheral causes: painful diabetic neuropathy, postherpetic neuralgia, trigeminal neuralgia, radiculopathy, vertebral canal stenosis, carpal tunnel syndrome, chemotherapy-induced neuropathy, post-traumatic and post-surgical neuropathy, phantom limb pain, and leprous neuritis (an important Indian cause).

Central causes: central post-stroke pain (thalamic or Déjerine–Roussy syndrome), spinal cord injury, multiple sclerosis, syringomyelia.

Mechanisms: peripheral sensitisation with upregulation of sodium channels (Nav1.7, Nav1.8) and ectopic ectopic discharge; central sensitisation and wind-up at the dorsal horn; loss of descending inhibitory modulation; deafferentation and cortical reorganisation.

Ageing alters pain processing: meta-analyses show a modest increase in pain threshold (which shortens the warning interval before tissue damage and leads to under-reporting of mild pain, increasing the risk of undiagnosed disease) but a decrease in pain tolerance.

Temporal summation of heat pain is greater and capsaicin-induced mechanical hyperalgesia lasts longer in older adults, indicating prolonged pain facilitation; endogenous pain inhibition is reduced. Net conclusion: severe pain is less well tolerated in older people.

Descriptors: burning, shooting, lancinating, electric-shock-like, pricking, tingling or squeezing pain in a neuroanatomical distribution; usually constant but may be paroxysmal, and typically worse at night.

Associated sensory disturbance: paraesthesiae and dysaesthesiae, allodynia, hyperalgesia and hyperpathia, often coexisting with sensory loss, impaired motor function, muscle atrophy or abnormal deep tendon reflexes.

Assessment: characterise the pain, map its distribution, examine for sensory signs, and identify the causative lesion. Screening tools include DN4, LANSS and painDETECT. Assess sleep, mood, function and the impact on activities of daily living.

Pain is a major determinant of frailty — in the English Longitudinal Study of Ageing, subjects reporting moderate to severe pain were more likely to become frail over the following eight years, independent of age, sex, lifestyle, depressive symptoms and socioeconomic factors.

Pain is not a symptom of dementia, but dementia impairs self-report and amplifies the impact of pain on function, mood, cognition and tolerance of adverse drug effects. Use observational tools (PAINAD, Abbey, DOLOPLUS-2) when self-report is unreliable.

First-line agents: gabapentinoids (gabapentin, pregabalin), serotonin–noradrenaline reuptake inhibitors (duloxetine, venlafaxine) and tricyclic antidepressants (amitriptyline, imipramine, nortriptyline).

Tricyclics are best avoided in older people because of their adverse effect profile, especially tertiary tricyclics such as amitriptyline. If a tricyclic is required, nortriptyline is the safer option. All TCAs can prolong the QT interval — obtain an ECG before starting. Cautions: arrhythmia, recent myocardial infarction, glaucoma and SIADH.

Pregabalin has linear, dose-proportional absorption, rapid onset and requires minimal titration; but acute kidney injury and rhabdomyolysis are recognised adverse effects — monitor renal function and creatine phosphokinase. Both gabapentinoids need dose reduction in renal impairment; sedation, dizziness and ataxia are the limiting effects in the elderly.

SNRIs lack antimuscarinic effects and are better tolerated than TCAs, but tend to raise heart rate and blood pressure — monitor blood pressure, pulse, creatinine and liver enzymes; avoid with monoamine oxidase inhibitors.

Second-line: tramadol and topical agents — 5% lidocaine patches and 8% capsaicin patches for peripheral neuropathic pain such as postherpetic neuralgia or post-traumatic neuropathy. Where there are concerns about the safety of systemic treatment, as in the frail elderly, lidocaine patches may be used as first-line therapy.

Strong opioids have been downgraded to third-line because of safety concerns.

Efficacy is modest — the number needed to treat for a 50% reduction in pain is 3.6 for tricyclics, 6.4 for SNRIs, 7.7 for pregabalin and 4.3 for strong opioids. Combination trials give inconsistent results, and the maximum tolerated dose of each drug is lower in combination, so titrate one agent at a time.

Carbamazepine remains first-line specifically for trigeminal neuralgia (oxcarbazepine as an alternative); monitor full blood count for aplastic anaemia and sodium for hyponatraemia, and beware interactions with warfarin and theophylline.

Not recommended: cannabinoids cannot be recommended for chronic pain in older people on current evidence; gabapentin and pregabalin are not supported for chronic back pain, exposing patients to risk without clear benefit.

Education is fundamental — the nature of pain, realistic expectations, and the benefits and risks of each option. Dispel the misconception that pain can always be eliminated; educate family and carers, particularly where there is cognitive impairment.

Cognitive-behavioural therapy, graded exercise, physiotherapy, TENS, acupuncture, desensitisation and mirror therapy. Effect sizes are small to moderate but the safety profile is better than drugs; used as an adjunct they permit lower drug doses and fewer adverse effects.

Interventional options for refractory pain: nerve blocks, epidural steroid injection, radiofrequency ablation, spinal cord stimulation, intrathecal therapy.

Prevention: recombinant zoster vaccination prevents herpes zoster and postherpetic neuralgia; good glycaemic and metabolic control reduces incident diabetic neuropathy; pyridoxine with isoniazid; and prompt corticosteroid treatment of leprous neuritis prevents permanent nerve damage.

Principles in the elderly: start low, go slow, one drug at a time, set realistic goals (30–50% pain reduction, improved sleep and function rather than freedom from pain), review regularly, and deprescribe if ineffective.