Elsevier

The Lancet

Volume 353, Issue 9168, 5 June 1999, Pages 1959-1964
The Lancet

Series
Neuropathic pain: aetiology, symptoms, mechanisms, and management

https://doi.org/10.1016/S0140-6736(99)01307-0Get rights and content

Summary

We highlight current theories about peripheral neuropathic pain and show that progress in management is contingent on targeting treatment not at the aetiological factors or the symptoms but at the mechanisms that operate to produce the symptoms. This approach will require substantial progress in our understanding of the pathophysiology of neuropathic pain, the development of accurate diagnostic tools to discover what mechanisms contribute to the pain syndrome in an individual, and effective treatments aimed specifically at the mechanisms.

Section snippets

Neuropathic pain is a pathological pain

The capacity to experience pain has a protective role: it warns us of imminent or actual tissue damage and elicits coordinated reflex and behavioural responses to keep such damage to a minimum. If tissue damage is unavoidable, a set of excitability changes in the peripheral and central nervous system establish a profound but reversible pain hypersensitivity in the inflamed and surrounding tissue. This process assists wound repair because any contact with the damaged part is avoided until

Aetiology of neuropathic pain

Neuropathic pain is currently classified on the basis of the aetiology of the insult to the nervous system or the anatomical distribution of the pain. Although this classification has some use for the differential diagnosis of the neuropathy, and for disease-modifying treatment if available, it offers no framework for clinical management of the pain. The relation between aetiology, mechanisms, and symptoms in this condition is complex (figure 1). The pain that manifests in diverse diseases may

Why does nerve injury cause pain?

Pain is normally elicited only when intense or damaging noxious stimuli activate high-threshold nociceptor primary sensory neurons. Peripheral neuropathic pain manifests as spontaneous pain (stimulus-independent pain) or pain hypersensitivity elicited by a stimulus after damage to or alterations in sensory neurons (stimulus-evoked pain). Normal neuronal function is contingent on the neuron itself, its supporting glial cells, and the environment with which it interacts. For example, the

Symptoms of neuropathic pain

Many patients with neuropathic pain exhibit persistent or paroxysmal pain that is independent of a stimulus. This stimulus-independent pain can be shooting, lancinating, or burning and may depend on activity in the sympathetic nervous system. Spontaneous activity in nociceptor C fibres is thought to be responsible for persistent burning pain and the sensitisation of dorsal horn neurons. Similarly, spontaneous activity in large myelinated A fibres (which normally signal innocuous sensations) is

Stimulus-independent pain

Two types of sodium channel are found in sensory neurons; the first type are sensitive to tetrodotoxin, a potent puffer-fish toxin, and the second type are insensitive to tetrodotoxin. The channels that are sensitive to tetrodotoxin are responsible for the initiation of the action potential and exist in all sensory neurons. By contrast, channels that are insensitive to tetrodotoxin are found only on nociceptor sensory neurons, have much slower activation and inactivation kinetics than the

Mechanisms as the target of management

The relation between the mechanisms responsible for the symptoms of neuropathic pain, the molecular targets that underlie these mechanisms, current drug therapy of neuropathic pain, and the new agents under development are shown in the panel. Knowledge about the mechanisms that produce neuropathic pain has advanced through laboratory investigation and quantitative sensory testing of symptoms in patients, the latter shows whether the pain is mediated centrally or peripherally and which fibre

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