Adrenergic mediation of SMP: Via nociceptive or non-nociceptive afferents or both?

Abstract

R ecent animal experiments have provided neurophysiological ly based evidence that after nerve injury or alteration of tissue biochemistry a limited population of nociceptive afferents become noradrenergically responsive to sympathetic efferent activity. Campbell et al. (the authors) have integrated this evidence, their own data, and psychophysical data from LaMotte et al. 2 and Simone et al. 9 to provide a testable modification of sympathetically maintained pain (SMP) theory. Their proposal is particularly appealing insofar as it offers a mechanism to explain the rapid relief of pain that occurs in some causalgia/ref lex sympathetic dystrophy (RSD)/SMP patients following sympathetic intervention. As recognized by Price et al. s (target citation) rapid relief of SMP by sympathetic blockade has remained difficult to explain on the basis of prior theory. The authors' model is based upon four mini-hypotheses: (1) up-regulation of adrenoreceptors occurs in nociceptive afferents (and, by implication, in only nociceptive afferents); (2) sympathetic activation of these nociceptive afferents is responsible for ongoing or spontaneous pain in SMP condit ions; (3) persistent sympathetic activation of these up-regulated nociceptive afferents produces a labile central sensitization upon which, in SMP, the hyperalgesic (allodynic) quality of non-nociceptive afferent activity is based; and (4) the culprit in SMP is the alpha-1 adrenoreceptors in up-regulated nociceptors.