Complexity of systems and actions underlying neurogenic inflammation

Excerpt

All components of the body from skin to soft tissue to all visceral organs and bone receive extensive innervation arising from the dorsal roots. Dating to the expression of the “Law of Bell and Magendie”, this innervation is considered to represent the pathway by which afferent or sensory input to the cord occurs. As reviewed in great detail by Valente and Brain [1] in this issue, work in the early twentieth century confounded this notion, with Stricker [2] and later Bayliss [3] demonstrating that information traveling antidromically in the dorsal root could have significant augmenting effects upon peripheral blood flow in a manner independent of the innervation provided by the sympathetic nerves (leading typically to reduced flow), suggesting a “motor” function of this pathway. The role of the sensory afferents was further suggested by the absence of vasodilation after cutaneous denervation [4]. Sensory innervation may vary in its precise composition, but invariably it possesses axons which are myelinated and unmyelinated. A telling association was made by Hinsey and Gasser [5], who showed that cutaneous vasodilation evoked by antidromic stimulation of sensory nerves occurred only if the stimulus was of sufficient intensity to evoke a slowly conducting C fiber potential wave. Following a long and winding pathway, which included the isolation of the peptide substance P (SP) from the dorsal roots and its identification as a vasodilator [6] with a role in plasma extravasation elicited by antidromic stimulation secondary to release of such a neuromediator from chemosensitive small-diameter afferent fibers [7]. Pretreatment of adult rats with the pungent capsaicin resulted in local vasodilation, acute pain behavior, and persistent morphological changes [8] with an associated functional impairment of chemosensitive C fibers [9]. These observations merged with the classic appreciation that a neuron releasing products at one terminal will release those products at all of its terminals, a variant professed by Eccles [10] of the original expression of the classic Dales law [11]. So, here we are today. These observations and the contents of this issue inspire several thoughts by the editors and we encourage the reader to consider their implications for their own favored system. …