The sensations that characterize neuropathic pain vary and are often multiple—burning, gnawing, aching, and shooting or lancinating qualities are described. There is a frequent association with the symptoms of hyperesthesia, hyperalgesia, allodynia, or hyperpathia. The abnormal sensations coexist in many cases with a sensory deficit and local autonomic dysfunction. Furthermore, chronic pain of neuropathic injury generally responds less well to treatment in comparison to acute pain. The following are the main types of neurogenic pain.
Pain states of peripheral nerve origin, for which the term neuropathic is more strictly applicable, far outnumber those caused by spinal cord, brainstem, thalamic, and cerebral disease. Although the pain is localized to a sensory territory supplied by a nerve, plexus or nerve root, it often radiates to adjacent areas. Sometimes the onset of pain acuity follows an injury; more often it appears at some point during the evolution or recession of the disorder. The disease of the nerve may be obvious, expressed by the usual sensory, motor, reflex, and autonomic changes, or these changes may be undetectable by standard tests. In the latter case, the term neuralgia is used.
The postulated mechanisms of peripheral nerve pain are diverse and differ from those of central diseases. Some of the major ideas were mentioned in the earlier section on chronic pain. One mechanism is denervation hypersensitivity, first described by Walter Cannon. He noted that when a group of neurons is deprived of its natural innervation, they become hyperactive. Others point to a reduced density of certain types of fibers in nerves supplying a causalgic zone as the basis of the burning pain but the comparison of the density of nerves from painful and nonpainful neuropathies has not proved to be consistently different. For example, Dyck and colleagues, in a study of painful versus nonpainful axonal neuropathies, concluded that there was no difference between them in terms of the type of fiber degeneration. Also, the occurrence of ectopic impulse generation all along the surface of injured axons and the possibility of ephaptic activation of unsheathed axons seem applicable particularly to some causalgic states. Stimulation of the nervi nervorum of larger nerves by an expanding intraneural lesion or a vascular change was postulated by Asbury and Fields as the mechanism of nerve trunk pain. The sprouting of adrenergic sympathetic axons in response to nerve injury has already been mentioned and is an ostensible explanation for the abolition of some cases of causalgic pain by sympathetic blockade. This has given rise to the term sympathetically sustained pain for some cases of causalgia, as discussed below.
Regenerating axonal sprouts, as in a neuroma, are also hypersensitive to mechanical stimuli. On a molecular level, it has been shown that voltage-gated sodium channels accumulate at the site of a neuroma and all along the axon after nerve injury, and that this gives rise to ectopic and spontaneous activity of the sensory nerve cell and its axon. Such firing has been demonstrated in humans after nerve injury. This mechanism is concordant with the relief of neurogenic pain by sodium channel-blocking antiepileptic drugs. Spontaneous activity in nociceptive C fibers is thought to give rise to burning pain; firing of large myelinated A fibers is believed to produce dysesthetic pain induced by tactile stimuli. The abnormal response to stimulation is also influenced by sensitization of central pain pathways, probably in the dorsal horns of the spinal cord, as outlined in the review by Woolf and Mannion. Hyperalgesia and allodynia are thought to result from such a spinal cord mechanism. Several observations have been made regarding the neurochemical mechanisms that might underlie these changes but none provides a consistent explanation. Possibly more than one of these mechanisms is operative in a given peripheral nerve disease.