Pathophysiology of pain - neuropathic

Definition

Neuropathic pain arises from damage or dysfunction of the nervous system itself (peripheral nerve, plexus, spinal cord, or brain) rather than from ongoing tissue injury detected by intact nociceptors - a fundamentally different mechanism requiring different treatment
Common in advanced cancer from direct tumour infiltration/compression of nerves or plexuses, and also from cancer treatment itself (chemotherapy-induced peripheral neuropathy, post-surgical/post-radiotherapy nerve injury)

Nerve injury/dysfunction causes aberrant, spontaneous, or amplified signalling along the damaged pathway - peripheral sensitisation (damaged nerve fibres becoming spontaneously active or abnormally sensitive) and central sensitisation (amplified processing in the spinal cord/brain) both contribute, explaining why neuropathic pain can persist or even worsen despite no ongoing tissue damage at the original injury site

Classic descriptors: burning, shooting, electric shock-like, stabbing, often with associated allodynia (pain from a normally non-painful stimulus, e.g. light touch) or hyperalgesia (exaggerated pain response to a normally painful stimulus) - these qualitative descriptors, plus a distribution matching a nerve/dermatomal/plexus territory, distinguish it clinically from nociceptive pain

Poorly responsive to opioids alone compared with nociceptive pain (though opioids may still provide partial benefit and remain part of a combined regimen) - adjuvant agents are central: gabapentinoids (gabapentin, pregabalin), tricyclic antidepressants (amitriptyline, nortriptyline), and SNRIs (duloxetine) all have evidence for neuropathic pain specifically
Combination therapy (an adjuvant plus an opioid) is common, since neuropathic pain frequently coexists with a nociceptive component ("mixed pain") rather than occurring in pure isolation

Chemotherapy-induced peripheral neuropathy, tumour infiltration of a nerve plexus (e.g. brachial or lumbosacral plexopathy), post-herpetic neuralgia, phantom limb pain

Recognising a neuropathic component (from the pain's specific quality and distribution, not simply from its severity) is essential, since escalating opioid dose alone in pure or predominantly neuropathic pain produces diminishing returns and disproportionate side effects without adding an appropriate adjuvant agent

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