Evidence Supporting a Role for Autonomic Modulation of C‐Low Threshold Mechanoreceptors

Abstract

C‐low threshold mechanoreceptors (LTMRs) are a functionally distinct class of cutaneous sensory fibers believed to facilitate the sensing and coding of pleasurable touch. These afferents have also been implicated in neuropathic pain states including allodynia, in which normally innocuous tactile stimuli elicit painful sensations. The mechanisms that mediate changes in C‐LTMR function are incompletely understood. Autonomic activity has been implicated in the maintenance of various pain syndromes, yet increases in autonomic neural activity do not seem to influence the firing properties of cutaneous nociceptors. Autonomic modulation of cutaneous C‐LTMRs may contribute to allodynia and neuropathic pain, but this has not been studied. We developed an in vitro isolated truncal skin‐nerve preparation to study the recruitment properties of C‐LTMRs following optical stimulation of skin (TH::CHR2 mice) and the actions of modulatory transmitters when bath applied to the subcutaneous interior side of the skin. Extracellular spike recordings were obtained from dorsal cutaneous nerves. Optogenetic recruitment of C‐LTMRs was temperature sensitive with lower temperatures recruiting more units. Recruited C‐LTMRs had typical conduction velocities (ranging from 0.35 to 0.5 m/s) and an average spike half‐width of 0.53 ms (+/− 0.2ms). We assessed fatigability in response to repetitive optical stimuli at 10 Hz. Consistent with previous reports C‐LTMRs were highly fatigable, especially at higher temperatures. Application of acetylcholine resulted in increased spontaneous afferent activity, reduced C‐LTMR recruitment, and increased fatigability. Application of the cholinesterase inhibitor neostigmine also depressed C‐LTMR recruitment. Norepinephrine also decreased recruitment and increased fatigability but reduced the incidence of spontaneous activity. The norepinephrine transport inhibitor clomipramine also reduced C‐LTMR recruitment. Serotonin did not result in changes to recruitment or fatigability of C‐LTMRs, but increased spontaneous activity. However, the serotonin transport inhibitor citalopram did reduce C‐LTMR recruitment. Similarly, dopamine administration had no effect, but application of the dopamine transport inhibitor buproprion depressed C‐LTMR recruitment. We conclude that C‐LTMR activity can be modified by neuromodulatory transmission and studies are underway to further characterize this effect.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.