Patients with peripheral neuropathy commonly express positive sensory symptoms, such as paresthesias, dysesthesias and different types of pain. As opposed to negative sensory phenomena whose electrophysiological correlate can be readily measured through conventional laboratory methods, the study of positive sensory phenomena is problematic.
Recent microneurographic techniques permit recording from individual C-fibers and allow their segregation into different functional classes. Systematic recordings of peripheral nociceptors from patients or from many animal models of neuropathic pain have been performed over the past years. It has become clear that neuronal hyperexcitability in peripheral nociceptors is an important mechanism of spontaneous neuropathic pain as it leads to the generation of ectopic impulses in pain fibers. These ectopically generated impulses contribute a direct afferent input into the central nervous system that leads to the experience of spontaneous pain.
Particularly important for the study of neuropathic pain is the recording from mechano-sensitive as well as mechano-insensitive (or silent) C-nociceptors. Different abnormalities have been identified in neuropathic pain patients: spontaneous impulse generation, sensitization to mechanical, heat and cold stimuli, and “multispike” responses. In acquired neuropathy, this phenomenon does not occur in all types of C nociceptors but is restricted to certain types of peripheral C-nociceptors: the mechano-insensitive, peptidergic, NGF-dependent C-nociceptor, whereas in inherited painful neuropathies spontaneous activity occurs in both nociceptor classes.
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