Involvement of Cutaneous Sensory Corpuscles in Non-Painful and Painful Diabetic Neuropathy

Abstract

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.

Revealing the Meissner Corpuscles in Human Glabrous Skin Using In Vivo Non-Invasive Imaging Techniques

“…One important limitation of the present study is the age range of participants from 26 to 55 years. For older individuals (>65 years), an increased keratinization and a breakdown of both the dermal–epidermal junction and the sensory corpuscles, such as MCs, has been reported [ 16 , 27 ]. Future investigations will address the morphology of the protrusions in individuals of high age.…”

“…Most clinical studies focused on intraepithelial nerve fibers, while few investigated how the number or quality of corpuscles in human skin changes with pathologies of the peripheral or central nervous system [ 14 , 15 ]. Variations in the amount, physiology, and distribution of MCs can potentially serve as markers for disorders or patients with healing problems from diabetic neuropathy, as described by Garcia-Mesa et al [ 16 ]. However, biopsies are an invasive and uncomfortable method to quantify mechanoreceptors in healthy participants in fundamental physiology studies.…”

Relationship of PIEZO1 and PIEZO2 vascular expression with diabetic neuropathy

“…The subjects included in this study were used previously in our published manuscript about changes in cutaneous sensory corpuscles associated with painful and painless DPN ( García-Mesa et al, 2021 ).…”

Cutaneous‐immuno‐neuro‐endocrine (CINE) system: A complex enterprise transforming skin into a super organ

“…The preganglionic/presynaptic neurons of PSNS arises from medulla oblongata (within the nuclei of oculomotor, III cranial nerve {Edinger‐Westphal}; facial, VII cranial nerve, {superior salivatory nucleus}; glossopharyngeal, IX cranial nerve {inferior salivatory nucleus} and vagus, X cranial nerve {dorsal nucleus of vagus nerve and nucleus ambiguous}) and lateral horn of sacral spinal cord (S2‐S4) and mediate cholinergic response via ACh. The exact function of PSNS innervation in skin is not known 67,70,72–75 …”