Adrenosensitivity of injured afferent neurons does not require the presence of postganglionic sympathetic terminals.
Nerve injury sometimes triggers neuropathic pain states that are exacerbated by sympathetic efferent activity. A classic example is causalgia. The mechanism of coupling between sympathetic efferent activity and the afferent discharge responsible for pain sensation is a subject of controversy. Some authors hold to the 'direct coupling hypothesis' which proposes that noradrenaline (NA), released from sympathetic varicosities, acts directly on alpha-adrenoreceptors located in the membrane of injured primary afferents. Others believe that coupling is indirect; that the effects of NA are mediated by additional, non-adrenergic, chemical substances and their receptors (the 'indirect coupling hypothesis'). For example, it has been proposed that in inflamed skin NA acts back on the sympathetic endings which, secondarily, release a prostanoid mediator which sensitizes afferent endings. We report that the responsiveness of injured afferent axons to systemically applied NA persists, and in fact increases in prevalence, in rats that underwent prior chemical or surgical sympathectomy. The observation of adrenosensitivity in injured afferents in the absence of sympathetic postganglionic endings is consistent with the direct coupling hypothesis, which associates adrenosensitivity with the injured afferent axon. It is not consistent with the indirect coupling hypothesis which requires the presence of sympathetic endings as a source for NA-evoked prostanoid release.
Rubin
G
G
Department of Neurosurgery, Rabin Medical Center (Beilinson Campus), Petah-Tiqva, Israel.
Kaspi
T
T
Rappaport
Z H
ZH
Cohen
S
S
Ravikovitch
M
M
Lomazov
P
P
Devor
M
M
D000316:Adrenergic alpha-Agonists / Q000378:metabolism*; D000818:Animals; D008297:Male; D009411:Nerve Endings / Q000502:physiology*; D009475:Neurons, Afferent / Q000502:physiology*; D009638:Norepinephrine / Q000502:physiology*; D016627:Oxidopamine; D051381:Rats; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000293:injuries; D013562:Sympathectomy / Q000379:methods; D013563:Sympathectomy, Chemical; D017779:Sympathetic Fibers, Postganglionic / Q000502:physiology*
D000316:Adrenergic alpha-Agonists; D016627:Oxidopamine; D009638:Norepinephrine