ABSTRACT
The mechanisms by which a noxious or nociceptive stimulus is evoked, propagated, integrated, and finally perceived are extremely complex. At each of these functional steps there is a delicate balance betwen excitatory and inhibitory influences from local, remote, and global factors. In neuropathic conditions this process becomes profoundly more complicated owing to both the interruption of the normal ‘‘wiring’’ of the system and the dynamic compensatory responses that occur throughout the nervous system. Some of these changes, which encompass anatomical, immune, and endocrine responses, among many others, are gradually reversed in concert with ‘‘healing’’ of the nerve injury. Other changes are more permanent and persist despite resolution of the original neuropathic insult. This latter group is likely to correlate closely with, and may be in part responsible for, chronic neuropathic pain syndromes.
