Origins of antidromic activity in sensory afferent fibers and neurogenic inflammation

Abstract

Neurogenic inflammation results from the release of biologically active agents from the peripheral primary afferent terminal. This release reflects the presence of releasable pools of active product and depolarization-exocytotic coupling mechanisms in the distal afferent terminal and serves to alter the physiologic function of innervated organ systems ranging from the skin and meninges to muscle, bone, and viscera. Aside from direct stimulation, this biologically important release from the peripheral afferent terminal can be initiated by antidromic activity arising from five anatomically distinct points of origin: (i) afferent collaterals at the peripheral-target organ level, (ii) afferent collaterals arising proximal to the target organ, (iii) from mid-axon where afferents lacking myelin sheaths (C fibers and others following demyelinating injuries) may display crosstalk and respond to local irritation, (iv) the dorsal root ganglion itself, and (v) the central terminals of the afferent in the dorsal horn where local circuits and bulbospinal projections can initiate the so-called dorsal root reflexes, i.e., antidromic traffic in the sensory afferent.

Nerves in Bone: Evolving Concepts in Pain and Anabolism

“…In addition, these neurons can generate efferent signals, often in the form of dorsal root reflexes, that are directed toward their peripheral targets. In general, this antidromic activity can arise from collateral axon branches within or proximal to the target tissue, from the dorsal root ganglia, or from central or local circuits in the dorsal horn . The efferent activity of primary sensory neurons is most evident in neurogenic inflammation following tissue injury, where release of neuropeptides such as calcitonin gene‐related peptide (CGRP) and substance P (SP) promotes vasodilation and plasma extravasation, respectively .…”

“…In general, this antidromic activity can arise from collateral axon branches within or proximal to the target tissue, from the dorsal root ganglia, or from central or local circuits in the dorsal horn. (11) The efferent activity of primary sensory neurons is most evident in neurogenic inflammation following tissue injury, where release of neuropeptides such as calcitonin gene-related peptide (CGRP) and substance P (SP) promotes vasodilation and plasma extravasation, respectively. (12) The presence of neurogenic inflammation within bone is supported by a study in rats in which chemical sensory denervation suppressed vasodilation and inflammatory cell recruitment within the bone marrow after induction of adjuvantinduced arthritis.…”

Complexity of systems and actions underlying neurogenic inflammation

“…The classic work relating to the dorsal root reflex (DRR) of Barron and Mathews [16,17] clearly point to antidromic activity arising from the central terminal in the uninjured, normally functioning afferent secondary to focal depolarization in the dorsal horn after an afferent barrage. Finally, of additional interest is the fact that, as reviewed by Sorkin et al in this issue [15], such DRRs can be initiated by bulbospinal projections. [18] Such linkages point to mechanisms whereby supraspinal systems can regulate peripheral afferent terminal excitability.…”

“…While the classic notion is that the peripheral terminal release represents excitation arising from the local axon collateral, the review by Sorkin and colleagues [15] emphasizes that classical physiology has long pointed to the generation of This article is a contribution to the special issue on Neurogenic Inflammation -Guest Editors: Tony Yaksh and Anna Di Nardo antidromic activity from different parts of the afferent structure including: mid-axon (as after nerve compression or focal injury), the dorsal root ganglia and the central (spinal) terminal. Further, much work is being undertaken today emphasizing that as the DRG lies outside the blood-brain barrier, its excitability can be regulated by circulating products and inflammatory cells such as macrophages.…”

“…An interesting variant on this theme is that afferent axon collaterals also project into the DRG. As reviewed in the Sorkin article [15], peptidergic collaterals are observed in the DRG. These afferent axon collaterals thus deliver terminal neurotransmitters to cells within the dorsal root ganglion.…”