Transient receptor potential (TRP) cation channel subfamily M member 3 (TRPM3), a member of the TRP channel superfamily, was recently identified as a nociceptor channel in the somatosensory system, where it is involved in the detection of noxious heat; however, owing to the lack of potent and selective agonists, little is known about other potential physiological consequences of the opening of TRPM3. Here we identify and characterize a synthetic TRPM3 activator, CIM0216, whose potency and apparent affinity greatly exceeds that of the canonical TRPM3 agonist, pregnenolone sulfate (PS). In particular, a single application of CIM0216 causes opening of both the central calcium-conducting pore and the alternative cation permeation pathway in a membrane-delimited manner. CIM0216 evoked robust calcium influx in TRPM3-expressing somatosensory neurons, and intradermal injection of the compound induced a TRPM3-dependent nocifensive behavior. Moreover, CIM0216 elicited the release of the peptides calcitonin gene-related peptide (CGRP) from sensory nerve terminals and insulin from isolated pancreatic islets in a TRPM3-dependent manner. These experiments identify CIM0216 as a powerful tool for use in investigating the physiological roles of TRPM3, and indicate that TRPM3 activation in sensory nerve endings can contribute to neurogenic inflammation.
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http://dx.doi.org/10.1073/pnas.1419845112 | DOI Listing |
Nat Commun
January 2025
Institute of Developmental Biology and Neurobiology, Faculty of Biology, Johannes Gutenberg University Mainz, Mainz, Germany.
After a peripheral nerve injury, Schwann cells (SCs), the myelinating glia of the peripheral nervous system, convert into repair cells that foster axonal regrowth, and then remyelinate or re-ensheath regenerated axons, thereby ensuring functional recovery. The efficiency of this mechanism depends however on the time needed for axons to regrow. Here, we show that ablation of histone deacetylase 8 (HDAC8) in SCs accelerates the regrowth of sensory axons and sensory function recovery.
View Article and Find Full Text PDFReg Anesth Pain Med
January 2025
State University of Campinas, Campinas, SP, Brazil.
Background/importance: Local anesthetic (LA) mixtures are used in peripheral nerve blocks (PNB) to improve onset, though study results remain conflicting.
Objective: This systematic review and meta-analysis compared the efficacy outcomes of long-acting LA to their mixture with shorter-acting LA in ultrasound-guided PNB. The primary outcome was sensory block onset.
Small Methods
January 2025
Department of Electrical and Computer Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea.
Recently, implantable devices for treating peripheral nerve disorders have demonstrated significant potential as neuroprosthetics for diagnostics and electrical stimulation. However, the mechanical mismatch between these devices and nerves frequently results in tissue damage and performance degradation. Although advances are made in stretchable electrodes, challenges, including complex patterning techniques and unstable performance, persist.
View Article and Find Full Text PDFJ Clin Gastroenterol
January 2025
Department of Surgery, Oncology and Gastroenterology, University of Padua.
Among the various factors implicated in the pathogenesis of gastroesophageal reflux disease (GERD), visceral hypersensitivity and mucosal resistance have been recently re-evaluated in relation to the increasing phenomenon of proton pump inhibitor failure, particularly in patients with nonerosive reflux disease (NERD). Intensive research has allowed us to understand that noxious substances contained in the refluxate are able to interact with esophageal epithelium and to induce the elicitation of symptoms. The frequent evidence of microscopic esophagitis able to increase the permeability of the mucosa, the proximity of sensory afferent nerve fibers to the esophageal lumen favoring the higher sensitivity to noxious substances and the possible activation of inflammatory pathways interacting with sensory nerve endings are pathophysiological alterations confirming that mucosal resistance is impaired in GERD patients.
View Article and Find Full Text PDFZhongguo Zhen Jiu
January 2025
Department of Pain Medicine, Suizhou Hospital of Hubei University of Medicine, Suizhou 441300, China.
Objective: To evaluate the clinical efficacy of ultrasound-guided needle knife release with different pathways for carpal tunnel syndrome (CTS).
Methods: Sixty CTS patients were randomly divided into a transverse group and a longitudinal group, with 30 patients in each group. The transverse group received the needle knife release under ultrasound above and below the median nerve along the short axis, while the longitudinal group received the needle knife release under ultrasound above the median nerve along the long axis.
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