Mechanical and cold polymodality coexist in tactile peripheral afferents, and it's not mediated by TRPM8

Abstract

In the mammalian somatosensory system, polymodality is defined as the competence of some neurons to respond to multiple forms of energy (e.g., mechanical and thermal). This ability is thought to be an exclusive property of nociceptive neurons (polymodal C-fiber nociceptors) and one of the pillars of nociceptive peripheral plasticity. The current study uncovered a completely different neuronal sub-population with polymodal capabilities on the opposite mechanical modality spectrum (tactile). We have observed that several tactile afferents (1/5) can respond to cold in non-nociceptive ranges. These cells' mechanical thresholds and electrical properties are similar to any low-threshold mechano-receptors (LT), conducting in a broad range of velocities (Aδ to Aβ), lacking CGRP and TRPM8 receptors. Due to its density, cold-response range, speed, and response to injury (or lack thereof), we speculate on its role in controlling reflexive behaviors (wound liking and rubbing) and modulation of nociceptive spinal cord integration. Further studies are required to understand the mechanisms behind this neuron's polymodality, central architecture, and impact on pain perception.

Keywords: Polymodality; cold; mechano-receptors; pain; somatosensory system.

Figure 1.

MC neuron’s polymodal response. (a) Schematic of the T11 in vivo model for physiological intracellular recording. (b) Study and activation protocol (CBP: cellular basal properties, RF: receptor field, SAP: cellular somatic properties, MT: mechanical threshold, CV: conduction velocity). (c) Relation between CV and AP D50 (LT: low threshold mechano-receptors, MC: mechano-cold polymodal receptors, AHT: fast conducting A fiber high threshold mechano-receptors, CHT: slow conducting C fiber high threshold mechano-receptors). (d) Typical MC spike (black) presented with the first derivative of the voltage (red). E and (f) MC response to mechanical stimulation (IFmax: Cellular instantaneous maximal frequency, Stm: applied stimuli, CR: cellular response). G and (h) MC response to cold (same cell as E). (i) Stained MC neuron IHC (NB: Neurobiotin). Scale bars: E (1 s), F (0.25 s), G (20 s), H (10 s), I (60×, 25 μm).