SeriesNeuropathic pain: aetiology, symptoms, mechanisms, and management
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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