Heat‐evoked vasodilatation in human hairy skin: axon reflexes due to low‐level activity of nociceptive afferents.

Abstract

1. Spreading vasodilatation of the axon reflex type was evoked by contact heat stimulation of the hairy skin in the human forearm (13X3 cm2 stimulus area) and was detected by laser Doppler flowmetry at 8, 19 and 30 mm distance.2. From a base temperature of 350, rapidly rising short heat stimuli (4°C s-1, 2 s plateau) elicited vasodilatation at an average threshold of 39 4 0C. For slowly rising sustained heat stimuli (64 s duration) the average threshold was 39-6 0C (n.s.). Laser Doppler flowmetry revealed a rapid onset within about 4 s, a long duration of several minutes beyond the end of the stimulus, and a rapid spread of vasodilatation to remote skin areas. These characteristics are typical for vasodilatation by an axon reflex of nociceptive afferents. 3. Axon reflex thresholds matched the lower range of C fibre nociceptor heat thresholds.Thermal stimuli that were adjusted to elicit about half-maximal phasic responses in warm fibres (steps from 30 to 350), but were below the range of C fibre nociceptor thresholds, did not cause any vasodilatation. 4. Pain thresholds were higher than axon reflex thresholds for both rapidly and slowly rising heat stimuli and strongly depended on the stimulus pattern (40-1 0C for rapidly rising stimuli and >430C for slowly rising stimuli). This observation is consistent with recent reports that the phasic response of nociceptive afferents is essential to overcome the summation requirements at central synapses. 5. In conclusion, axon reflex vasodilatation in response to heat stimuli in the hairy skin of humans is elicited by activation of heat-sensitive nociceptors, even in the absence of a conscious perception of heat pain. The dissociation of pain and vasodilatation thresholds supports the concept of two operating ranges of primary nociceptive afferents. Warm fibres do not contribute to axon reflex vasodilatation in the hairy skin of the human forearm. Release of vasoactive peptides by nociceptive primary afferents may also contribute to local heat-evoked vasodilatation at temperatures above 400C.

Sensory and sympathetic nerve contributions to the cutaneous vasodilator response from a noxious heat stimulus

“…• C), vasoactive peptides are released in large quantities by nociceptive primary afferents, resulting in a significant increase in SkBF (Magerl & Treede, 1996). The distinctive SkBF patterns witnessed in the present study seem to support claims made by Minson et al (2002), who suggested that a smaller initial peak might be associated with a greater risk of local tissue damage in response to direct heat.…”

Prevalence of somatic small fiber neuropathy in obesity

“…15 For example, excitation of C-fiber discharges need not be associated with pain sensation but can evoke a flare response. [11][12][13][14] The two may have different sensory/efferent pathways, and/or different sub-sets of nociceptors. 15,33 The difference in the flare and pain response to a heat-ramp stimulus among the normal and obese subjects may be indicative of such a dissociation and, in fact, would favor a concept that the organism attempts to elicit an early protective reaction (neurogenic vasodilatation) at a temperature (441C) just below that which will become injurious to tissue.…”

“…15,33 The difference in the flare and pain response to a heat-ramp stimulus among the normal and obese subjects may be indicative of such a dissociation and, in fact, would favor a concept that the organism attempts to elicit an early protective reaction (neurogenic vasodilatation) at a temperature (441C) just below that which will become injurious to tissue. 14 Flare can be suppressed or abolished by denervation, 21,42 local anesthetics, 12,21 capsaicin-desensitization, 22,34 disease (diabetes, post-herpetic neuralgia), 21,43 and aging. 32 Under circumstances of prolonged depression of small fiber function, tissue integrity can be substantially impaired.…”

“…4 The Ad-and, more so, C-fiber primary afferent neurons involved in SSFN are notably nociceptors responding to noxious mechanical, thermal, and irritant chemical stimuli; but they can also be excited by non-noxious stimuli such as heat and transcutaneous electrical stimulation. [11][12][13][14][15] Although C-fibers convey pain signals to the CNS, they also have an 'efferent, or effector' function. Under normal physiological conditions, 16 C-fibers control vasodilatation of the skin microvasculature (arterioles), mediating axonreflexes locally 17 and/or centrally (dorsal root reflexes 18 ) by release of neuropeptides (e.g., calcitonin gene-related peptide, CGRP) from the terminals of the nociceptive afferents.…”

Relationships Between Skin Temperature and Temporal Summation of Heat and Cold Pain

“…Psychophysical thresholds for heat pain range from 40 to 49 for stimulation at glabrous and hairy skin sites with probes of different sizes and with widely varying ramp rates and stimulus durations (Hamalainen et al 1982;LaMotte 1984;LaMotte et al 1983;Morin and Bushnell 1998;Pertovaara et al 1996;Strigo et al 2000;Wahren et al 1989;Yarnitsky and Ochoa 1991). Most of the mean threshold values cluster between 43 and 46°C (Craig and Bushnell 1994;Dyck et al 1993;Hardy et al 1952;Harju 2002;Magerl and Treede 1996;Nielsen and Arendt-Nielsen 1998;Taylor et al 1993;Tillman et al 1995;Torebjork et al 1984;Verdugo and Ochoa 1992). In experiment 2 of this study, eVAS ratings of 10 represent a conservative estimate of threshold pain.…”