Peripheral Mechanobiology of Touch-Studies on Vertebrate Cutaneous Sensory Corpuscles

Abstract

The vertebrate skin contains sensory corpuscles that are receptors for different qualities of mechanosensitivity like light brush, touch, pressure, stretch or vibration. These specialized sensory organs are linked anatomically and functionally to mechanosensory neurons, which function as low-threshold mechanoreceptors connected to peripheral skin through Aβ nerve fibers. Furthermore, low-threshold mechanoreceptors associated with Aδ and C nerve fibers have been identified in hairy skin. The process of mechanotransduction requires the conversion of a mechanical stimulus into electrical signals (action potentials) through the activation of mechanosensible ion channels present both in the axon and the periaxonal cells of sensory corpuscles (i.e., Schwann-, endoneurial- and perineurial-related cells). Most of those putative ion channels belong to the degenerin/epithelial sodium channel (especially the family of acid-sensing ion channels), the transient receptor potential channel superfamilies, and the Piezo family. This review updates the current data about the occurrence and distribution of putative mechanosensitive ion channels in cutaneous mechanoreceptors including primary sensory neurons and sensory corpuscles.

Keywords: Piezo2; acid-sensing ion channels; low-threshold mechanoreceptors; mechanoproteins; sensory corpuscles; skin; transient receptor potential channels.

Figure 1

Schematic representation of the afferent innervation of mammalian glabrous skin. Glabrous skin is supplied by myelinated and non-myelinated nerve fibers (Aβ, Aδ, C), originated from large, intermediate and small sized neurons (low-threshold mechanoreceptors (LTMRs) and nociceptors) localized in the dorsal root ganglia (DRG). Aβ nerve fibers end in the dermis forming different morphotypes of sensory corpuscles. Photos on the left side correspond to sections of Pacini’s corpuscles immunostained for neurofilament proteins (NFP) and S100 protein (S100P) to, respectively, label the axon (Ax; red immunofluorescence) and the Schwann-related cells (IC: inner core; green fluorescence). Right side photos correspond to a section of human lumbar DRG—immunostained for S100P and acid-sensing ion channel protein 2 (ASIC2). S100 protein labels satellite cells (arrows and green fluorescence) while neuronal cell bodies (asterisks and red fluorescence) display ASIC2 positivity.

Figure 2

Schematic representations and photos of the different sensory corpuscle morphotypes present in human digital glabrous and hairy skin. Aβ LTMRs contact with epithelial Merkel cells or Schwann-like cells forming Merkel cell–neurite complexes (Aβ slowly adapting (SA)I-LTMRs), Meissner corpuscles (Aβ rapidly adapting (RA)1-LTMRs), Pacinian corpuscles (Aβ RAII-LTMRs) and Ruffini endings (Aβ SAII-LTMRs). Hairs have a complex nervous apparatus that consists of lanceolate and circumferential endings as well as free nerve endings; occasionally, hairs have associated Merkel cells, Ruffini and even Pacinian corpuscles. Photos were obtained from sections of human digital and facial skin immunostained for neuron-specific enolase to label the central axon, i.e., the ending of Aβ low-threshold mechanoreceptors.

Figure 3

Schematic representation of the afferent innervation of mammalian hairy skin. Hairs form pilo–neural complexes with Aβ, Aδ, and C nerve fibers originated from large, intermediate and small sized primary sensory neurons localized in dorsal root ganglia (DRG). They form circumferential and longitudinal lanceolate endings around the hair follicle that work as RA-LTMRs, Aδ-LTMRs, and C-LTMRs. Guard hairs are innervated by Aβ RA-LTMR lanceolate endings; awl/auchene hairs by Aβ RA-LTMRs, Aδ-LTMRs and C-LTMRs lanceolate endings; and zigzag hairs by Aδ-LTMRs and C-LTMRs. Merkel cell touch domes are innervated by Aβ SAI-LTMRs. NSE: neuron-specific enolase; S100P: S100 protein; TRPC6: transient receptor potential canonical channel 6; TRPV4: transient-receptor potential vanilloid channel 4.

Figure 4

Expression of different putative mechanoproteins in cutaneous sensory corpuscles and human lumbar dorsal root ganglia (DRG). Brown boxes contain ion channels identified in LTMR axons or cells bodies, while blue boxes contain ion channels localized in Schwann-related cells of sensory corpuscles and satellite cells of DRG. Photos show localization of putative mechanoproteins in human cutaneous sensory corpuscles, Merkel cells and lumbar DRG.