The Relationship between Cutaneous C Fibre Type and Antidromic Vasodilatation in the Rabbit and the Rat

Abstract

Skin blood flow was monitored during antidromic stimulation of identified cutaneous C fibres in fine filaments dissected from the saphenous nerve of anaesthetized rabbits and rats. The techniques used to monitor skin blood flow were laser Doppler perfusion imaging and laser Doppler flowmetry. In the rabbit filaments a total of thirty‐three C fibres were tested for their ability to produce antidromic vasodilatation. The only C fibres found to have vasodilator actions were of the polymodal nociceptor afferent class, and fourteen (50%) of the twenty‐eight polymodal nociceptor units tested were vasoactive. The afferent receptive fields of polymodal nociceptor afferents were mapped carefully using suprathreshold mechanical stimuli, and there was a good correlation between afferent receptive field area and area of vasodilatation. In the rat, eleven of the fifty‐four C fibres antidromically stimulated had vasodilator actions. All eleven vasoactive C fibres were nociceptive and comprised seven polymodal nociceptor units, two heat nociceptor units and two incompletely classified nociceptor units. The area of increased blood flow was always coincident with the afferent field of the stimulated unit. In the rat the vasodilator units were not evenly distributed over the saphenous nerve receptive field. Nine of the eleven vasoactive C fibres had receptive fields located on the foot or the digits, and only two were on the ankle or lower leg. Overall, the population of nociceptive C fibres was evenly distributed over the saphenous nerve receptive field. In both the rabbit and the rat, a subclass of polymodal nociceptor afferents form the majority of the vasoactive units and will make the main contribution to axon reflex flare and other neurogenic inflammatory responses involving vasodilatation. The vasoactive polymodal nociceptor units tend to have relatively low mechanical sensitivity, although they have typical heat thresholds. In the rat heat nociceptor units also have vasodilator actions. However, such heat nociceptor units form a minor functional class of afferent C fibre in the rat saphenous nerve, and are not found in the rabbit saphenous nerve. The findings from this study in the rabbit and the rat are compared with the situation in pig skin. The close relationship between afferent receptive field area and spread of flare across species is noted, and the way these measures increase with body size is discussed.

Neuronal system-dependent facilitation of tumor angiogenesis and tumor growth by calcitonin gene-related peptide

“…Axon reflex elicited by nociceptive stimulation may be closely related to the increased release of CGRP from nerve endings. It has been suggested that the axon reflex in human skin is a response neurally mediated by C-fiber nociceptors, which have been shown to stimulate vasodilatation via the release of CGRP and substance P (23). The present results suggested that axon reflex-mediated CGRP release may be a key event involved in facilitation in tumor-associated angiogenesis.…”

A subpopulation of capsaicin‐sensitive porcine dorsal root ganglion neurons is lacking hyperpolarization‐activated cyclic nucleotide‐gated channels

“…For example, silent nociceptors are by far more abundant in man and pig than in rodents (Lynn and Carpenter, 1982;Handwerker et al, 1991;Lynn et al, 1995;Schmidt et al, 1995;Gee et al, 1997). For example, silent nociceptors are by far more abundant in man and pig than in rodents (Lynn and Carpenter, 1982;Handwerker et al, 1991;Lynn et al, 1995;Schmidt et al, 1995;Gee et al, 1997).…”

“…There is evidence that silent nociceptors are more abundant in human (Schmidt et al, 1995), monkey (Meyer et al, 1991), and pig (Lynn et al, 1995), than in rodents (Lynn and Carpenter, 1982;Handwerker et al, 1991;Gee et al, 1997). Moreover, it has been shown that the axon-reflex induced vasodilatation in skin is mediated by silent nociceptors in both man (Schmelz et al, 2000) and pig Sann and Pierau, 1998), but not in rodents (Gee et al, 1996).…”

Nociceptor sensitization to mechanical and thermal stimuli in pig skin in vivo

“…Mechanical thresholds, however, remained either unchanged (Andrew and Greenspan, 1999) or decreased upon constant suprathreshold (250 mN) mechanical stimulation (Du et al, 2006). In contrast to rodents (Gee et al, 1997), the sensitization of polymodal nociceptors alone would not entirely explain the generation of an axon reflex erythema recorded in the pig. It may be additionally hypothesized that in UV-B irradiated skin polymodal nociceptors also gain the ability to induce an axon reflex.…”