Specialized mechanoreceptor systems in rodent glabrous skin

Abstract

Key points An ex vivo preparation was developed to record from single sensory fibres innervating the glabrous skin of the mouse forepaw.The density of mechanoreceptor innervation of the forepaw glabrous skin was found to be three times higher than that of hindpaw glabrous skin.Rapidly adapting mechanoreceptors that innervate Meissner's corpuscles were severalfold more responsive to slowly moving stimuli in the forepaw compared to those innervating hindpaw skin.We found a distinct group of small hairs in the centre of the mouse hindpaw glabrous skin that were exclusively innervated by directionally sensitive D‐hair receptors.The directional sensitivity, but not the end‐organ anatomy, were the opposite to D‐hair receptors in the hairy skin.Glabrous skin hairs in the hindpaw are not ubiquitous in rodents, but occur in African and North American species that diverged more than 65 million years ago. AbstractRodents use their forepaws to actively interact with their tactile environment. Studies on the physiology and anatomy of glabrous skin that makes up the majority of the forepaw are almost non‐existent in the mouse. Here we developed a preparation to record from single sensory fibres of the forepaw and compared anatomical and physiological receptor properties to those of the hindpaw glabrous and hairy skin. We found that the mouse forepaw skin is equipped with a very high density of mechanoreceptors; >3 times more than hindpaw glabrous skin. In addition, rapidly adapting mechanoreceptors that innervate Meissner's corpuscles of the forepaw were severalfold more sensitive to slowly moving mechanical stimuli compared to their counterparts in the hindpaw glabrous skin. All other mechanoreceptor types as well as myelinated nociceptors had physiological properties that were invariant regardless of which skin area they occupied. We discovered a novel D‐hair receptor innervating a small group of hairs in the middle of the hindpaw glabrous skin in mice. These glabrous skin D‐hair receptors were direction sensitive albeit with an orientation sensitivity opposite to that described for hairy skin D‐hair receptors. Glabrous skin hairs do not occur in all rodents, but are present in North American and African rodent species that diverged more than 65 million years ago. The function of these specialized hairs is unknown, but they are nevertheless evolutionarily very ancient. Our study reveals novel physiological specializations of mechanoreceptors in the glabrous skin that likely evolved to facilitate tactile exploration.

Serial Histological Sectioning of the Intact Mouse Hind Paw for Quantification of the Anatomical Distribution of Meissner-like Corpuscles across the Skin

“…No other receptor types were identified with this preparation. Our observations are consistent with others who have found Meissner-like corpuscles in the glabrous skin of the mouse [12,15]. Pacinian corpuscles have not been found in rodent skin however they are abundant in the interosseous membrane of the rodent ulna and fibula [12].…”

“…This is an in vivo technique carried out in humans that involves the insertion of a microelectrode into a peripheral nerve to record neural activity in response to a stimulus [4]. Similar in vivo and ex vivo approaches to record responses from single sensory fibres have also been developed in mice to map single afferent centers in the glabrous hind paw skin [15,16]. Single afferent recordings, however, may not necessarily represent the sensory response of a single mechanoreceptor.…”

“…Single afferent recordings may arise from the combined responses of multiple terminal branches of a single afferent that each, presumably, end in a mechanoreceptor [17][18][19]. It is also possible that some mechanoreceptors are served by multiple afferents [15,18]. Thus, direct visualization of the hind paw skin using a histological approach is necessary to determine the anatomical location and density of mechanoreceptors across the entire foot sole.…”

“…Previous histological and microscopy studies of the mouse hind paw typically section and image isolated footpads or digits. As such, studies often infer about mechanoreceptor density across the entire hind paw based only on isolated histology in the pads and digits [13,15,24]. To fully understand how the distribution of mechanoreceptors across the foot sole correlates to its neurological responses, the hind paw glabrous skin must be fully visualized microscopically through serial sectioning.…”

Independent evolution of pain insensitivity in African mole-rats: origins and mechanisms

“…Despite the fact that cutaneous nerves in naked mole-rats have a depleted number of C-fiber nociceptors, our physiological studies have shown that the receptor properties of these neurons do not differ significantly from C-fibers in mice (Park et al 2008). This was the case for saphenous nerve Aδ-fibers with nociceptive properties, as well as for C-fiber nociceptors as measured using an ex vivo skin-nerve preparation (Milenkovic et al 2008;Moshourab et al 2013;Walcher et al 2018). The major C-fiber nociceptor population is classified as polymodal receptors (i.e., responding both to mechanical and thermal stimuli) and they make up the majority of C-fibers (60-70%) (Fleischer et al 1983;Koltzenburg et al 1997;Lewin and Moshourab 2004).…”