Adrenosensitivity of injured afferent neurons does not require the presence of postganglionic sympathetic terminals

Abstract

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.

Effect of Sympathetic and Parasympathetic Mediators on the Release of Calcitonin Gene-Related Peptide and Prostaglandin E2 from Rat Dura Mater, in vitro

“…C‐fibres of the skin of normal rats do not respond to NE but NE causes an excitation of the neurons in rats with inflammation (31). Comparable effects were also seen in other models (46–49). In the present experiments, care was taken to avoid any inflammation of the dura mater and the basal levels of CGRP were low, indicating non‐stimulated conditions.…”

The effect of stellate ganglion block on the atypical facial pain

“…Sympathetic activity may generate pain under certain pathological conditions. In sympathetically maintained pain cases, the receptors at the primary afferents can change and become sensitive to adrenergic substances such as norepinephrine [ 13 14 ]. It was reported that SGB is effective to reduce pain related to temporal arteritis and sympathetic maintained headache and orofacial pain [ 15 16 ].…”

Neural Acupuncture Unit: A New Concept for Interpreting Effects and Mechanisms of Acupuncture

“…The injured and migrated cells consequently release various neuroactive mediators, which infiltrate the tissues and act at corresponding receptors on the surface of afferent nerve terminals in NAUs via the axon reflex [17]. Meanwhile, tissue injury results in plastic changes in peripheral primary afferents, which develop synapse-like contacts with postganglionic sympathetic nerve varicosities, where NA release acts on α -adrenoceptors on afferent nerve terminals of NAUs [22, 23]. …”