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.

Distal diabetic sensorimotor polyneuropathy (DDSP) is the most prevalent form of diabetic neuropathy, and some of the patients develop gradual pain. Specialized sensory structures present in the skin encode different modalities of somatosensitivity such as temperature, touch, and pain. The cutaneous sensory structures responsible for the qualities of mechanosensitivity (fine touch, vibration) are collectively known as cutaneous mechanoreceptors (Meissner corpuscles, Pacinian corpuscles, and Merkel cell–axonal complexes), which results are altered during diabetes. Here, we used immunohistochemistry to analyze the density, localization within the dermis, arrangement of corpuscular components (axons and Schwann-like cells), and expression of putative mechanoproteins (PIEZO2, ASIC2, and TRPV4) in cutaneous mechanoreceptors of subjects suffering clinically diagnosed non-painful and painful distal diabetic sensorimotor polyneuropathy. The number of Meissner corpuscles, Pacinian corpuscles, and Merkel cells was found to be severely decreased in the non-painful presentation of the disease, and almost disappeared in the painful presentation. Furthermore, there was a marked reduction in the expression of axonal and Schwann-like cell markers (with are characteristics of corpuscular denervation) as well as of all investigated mechanoproteins in the non-painful distal diabetic sensorimotor polyneuropathy, and these were absent in the painful form. Taken together, these alterations might explain, at least partly, the impairment of mechanosensitivity system associated with distal diabetic sensorimotor polyneuropathy. Furthermore, our results support that an increasing severity of DDSP may increase the risk of developing painful neuropathic symptoms. However, why the absence of cutaneous mechanoreceptors is associated with pain remains to be elucidated.

PIEZO1 and PIEZO2 are essential components of mechanogated ion channels, which are required for mechanotransduction and biological processes associated with mechanical stimuli. There is evidence for the presence of PIEZO1 and PIEZO2 in teeth and periodontal ligaments, especially in cell lines and mice, but human studies are almost nonexistent. Decalcified permanent human teeth and mouse molars were processed for immunohistochemical detection of PIEZO1 and PIEZO2. Confocal laser microscopy was used to examine the co‐localization of PIEZO 1 and PIEZO2 with vimentin (a marker of differentiated odontoblasts) in human teeth. In the outer layer of the human dental pulp, abundant PIEZO1‐ and PIEZO2‐positive cells were found that had no odontoblast morphology and were vimentin‐negative. Based on their morphology, location, and the absence of vimentin positivity, they were identified as dental pulp stem cells or pre‐odontoblasts. However, in mice, PIEZO1 and PIEZO2 were ubiquitously detected and colocalized in odontoblasts. Intense immunoreactivity of PIEZO1 and PIEZO2 has been observed in human and murine periodontal ligaments. Our findings suggest that PIEZO1 and PIEZO2 may be mechanosensors/mechanotransducers in murine odontoblasts, as well as in the transmission of forces by the periodontal ligament in humans and mice.

The carotid sinus and the carotid body are major peripheral chemo- and baro(mechano)receptors that sense changes in arterial wall pressure and in oxygen, carbon dioxide, and pH in arterial blood. Recently, it was demonstrated that the PIEZO1 and PIEZO2 mechanoreceptor/mechanotransducers are responsible for the baroreflex in the murine aortic arch (aortic sinus). Furthermore, some experimental evidence suggests that the carotid body could participate in mechanosensing. In this study, we used immunohistochemistry and immunofluorescence in conjunction with laser confocal microscopy to study the distribution of PIEZO1 and PIEZO2 in the human carotid sinus and carotid body as well as in the petrosal ganglion of the glossopharyngeal nerve and the superior cervical sympathetic ganglion. PIEZO1 and PIEZO2 were detected in different morphotypes of sensory nerve formations in the walls of the carotid sinus and carotid artery walls. In the carotid body, PIEZO1 was present in a small population of type I glomus cells and absent in nerves, whereas PIEZO2 was present in both clusters of type I glomus cells and nerves. The most prominent expression of PIEZO1 and PIEZO2 in the carotid body was found in type II glomus cells. On the other hand, in the petrosal ganglion, around 25% of neurons were PIEZO1-positive, and around 85% were PIEZO2-positive; regarding the superior cervical sympathetic ganglion, around 71% and 86% displayed PIEZO1 and PIEZO2, respectively. The results of this study suggest that PIEZO1 and PIEZO2 could be involved in the detection and/or mechanotransduction of the human carotid sinus, whereas the role of the carotid body is more doubtful since PIEZO1 and PIEZO2 were only detected in some nerves and PIEZO2 was present in a small population of type I glomus cells, with PIEZO1 being absent in these cells. However, since immunoreactivity for PIEZO2 was detected in type II glomus cells, researchers should investigate whether these cells play a role in the detection of mechanical stimuli and/or participate in mechanotransduction.