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Background/Objectives: Tentonin-3/TMEM150C is a pore-forming protein of a mechanically activated channel recently identified that typically displays rapid activation followed by slow inactivation. It has been detected in murine dorsal root ganglia, nodose ganglion baroreceptors, and muscle spindles. Nevertheless, primary sensory neurons expressing tentonin-3/TMEM150C fall into the categories of nociceptors, mechanoreceptors, and proprioceptors. Methods: We used immunohistochemistry and image analysis (examining the size of the neuronal bodies in the dorsal root ganglia) to investigate the distribution of tentonin-3/TMEM150C in human cervical dorsal root ganglia, sensory nerve formations in the glabrous skin, especially cutaneous end-organ complexes or sensory corpuscles, and muscle spindles. Results: In dorsal root ganglia, 41% of neurons were tentonin-3/TMEM150C-positive, with a distribution of small (12.0%), intermediate (18.1%), and large (10.9%). In the glabrous skin, tentonin-3/TMEM150C was observed in the axon of Meissner, Pacinian, and Ruffini corpuscles as well as in the axon of the Merkel cell–axon complexes. Furthermore, tentonin-3/TMEM150C-positive axons were observed in muscle spindles. No free nerve endings displaying immunoreactivity were found. Conclusions: This is the first report on the distribution of tentonin-3/TMEM150C immunoreactivity in the human peripheral somatosensory system, and although it is a brief preliminary study, it opens new perspectives for the study of this new mechano-gated ion channel. Full article

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. Full article

Sensory corpuscles of human skin are terminals of primary mechanoreceptive neurons associated with non-neuronal cells that function as low-threshold mechanoreceptors. Structurally, they consist of an extreme tip of a mechanosensory axon and nonmyelinating peripheral glial cells variably arranged according to the morphotype of the sensory corpuscle, all covered for connective cells of endoneurial and/or perineurial origin. Although the pathologies of sensitive corpuscles are scarce and almost never severe, adequate knowledge of the structure and immunohistochemical profile of these formations is essential for dermatologists and pathologists. In fact, since sensory corpuscles and nerves share a basic structure and protein composition, a cutaneous biopsy may be a complementary method for the analysis of nerve involvement in peripheral neuropathies, systemic diseases, and several pathologies of the central nervous system. Thus, a biopsy of cutaneous sensory corpuscles can provide information for the diagnosis, evolution, and effectiveness of treatments of some pathologies in which they are involved. Here, we updated and summarized the current knowledge about the immunohistochemistry of human sensory corpuscles with the aim to provide information to dermatologists and skin pathologists. Full article

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. Full article