Decline of tactile sensation associated with ageing depends on modifications in skin and both central and peripheral nervous systems. At present, age‐related changes in the periphery of the somatosensory system, particularly concerning the effects on mechanoreceptors, remain unknown. Here we used immunohistochemistry to analyse the age‐dependent changes in Meissner's and Pacinian corpuscles as well as in Merkel cell‐neurite complexes. Moreover, variations in the neurotrophic TrkB‐BDNF system and the mechanoprotein Piezo2 (involved in maintenance of cutaneous mechanoreceptors and light touch, respectively) were evaluated. The number of Meissner's corpuscles and Merkel cells decreased progressively with ageing. Meissner's corpuscles were smaller, rounded in morphology and located deeper in the dermis, and signs of corpuscular denervation were found in the oldest subjects. Pacinian corpuscles generally showed no relevant age‐related alterations. Reduced expression of Piezo2 in the axon of Meissner's corpuscles and in Merkel cells was observed in old subjects, as well was a decline in the BDNF‐TrkB neurotrophic system. This study demonstrates that cutaneous Meissner's corpuscles and Merkel cell‐neurite complexes (and less evidently Pacinian corpuscles) undergo morphological and size changes during the ageing process, as well as a reduction in terms of density. Furthermore, the mechanoprotein Piezo2 and the neurotrophic TrkB‐BDNF system are reduced in aged corpuscles. Taken together, these alterations might explain part of the impairment of the somatosensory system associated with ageing.

Meissner corpuscles are cutaneous mechanoreceptors that are usually located in the dermal papillae of human glabrous skin. Structurally, these sensory corpuscles consist of a mechanoreceptive sensory neuron surrounded by non-myelinating lamellar Schwann-like cells. Some authors have described a partially developed fibroblastic capsule of endoneurial or perineurial origin around Meissner corpuscles; however, others have noted that these structures are non-encapsulated. As there is continuity between the periaxonic cells forming the sensory corpuscles and the cells of the nerve trunks, we used immunohistochemistry to examine the expression of endoneurial (CD34 antigen) or perineurial [Glucose transporter 1 (Glut1)] markers in human cutaneous Meissner corpuscles. We also investigated the immunohistochemical patterns of nestin and vimentin (the main intermediate filaments of the cytoskeleton of endoneurial and perineurial cells, respectively) in Meissner corpuscles. The most important finding from this study was that CD34-positive cells formed a partial/complete capsule of endoneurial origin around most Meissner corpuscles, without signs of other perineurial Glut1positive elements. However, the cytoskeletal proteins of the capsular CD34-positive cells did not include either nestin or vimentin, so the cytoskeletal composition of these cells remains to be established. Finally, the intensity of the immunoreactivity for CD34 in the capsule decreased with ageing, sometimes becoming completely absent in the oldest individuals. In conclusion, we report the first immunohistochemical evidence of the capsule of Meissner corpuscles in humans and demonstrate the endoneurial origin of the capsule.

Chondroitin sulfate is a glycosaminoglycan involved in maintaining the morphofunctional properties of the extracellular matrix in peripheral nerves, but its distribution in human sensory corpuscles is unknown despite the role of extracellular matrix in mechanotransduction and axonal guidance. In this study we used immunohistochemistry to analyze the distribution of chondroitin sulfate in human cutaneous Meissner and Pacinian corpuscles. Chondroitin sulfate expression was absent from Meissner corpuscles. In Pacinian corpuscles chondroitin sulfate was found associated to a CD34 positive endoneurial-related layer, interposed between the S100 protein positive inner core cells, and the vimentin positive inner core and outer core-capsule cells. Therefore, the intermediate CD34+/chondroitin sulfate+ intermediate layer present in Pacinian corpuscles isolates the neural segment of the corpuscles (axon and inner core) from the non-neural segments (outer core and capsule). These results suggest a role of chondroitin sulfate in the proper axonal growth and guidance, within the neuronal compartment of the Pacinian corpuscles during development and reinnervation, can be hypothesized. Moreover, a role of CS in mechanotransduction cannot be ruled out.

Mechanosensory afferents can be distinguished morphologically based on their sensory terminals in the skin (i.e. sensory corpuscles) and the speed with which they conduct action potentials; most of them respond to tactile stimuli with specific firing patterns (Rice and Albrecht, 2008; Gardner and Johnson, 2013). The dermis in vertebrate skin contains a variety of sensory corpuscles that mediate different types of sensibility, especially touch (McGlone and Reilly, 2010; McGlone et al., 2014). These structures, known as low-threshold mechanoreceptors (LTMRs), encode non-painful mechanical stimuli and relay the information to the peripheral pro

Vertebrate skin contains specialized sensory organs collectively referred to as sensory corpuscles, which are supplied by peripheral processes of primary sensory neurons that encode non-painful mechanical stimuli (low-threshold mechanoreceptors, LTMRs; Abraira & Ginty, 2013; Fleming & Luo, 2013; Zimmerman et al., 2014). A group of these structures localized in the erogenous zones are involved in sexual pleasure. In women, the glans clitoris is generally considered the structure most involved in sexual pleasure, and it is a key element required to reach orgasm. It is a fibrovascular, non-erectile, densely innervated structure located in the midline that is the only