{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T22:46:43Z","timestamp":1792709203208,"version":"4.5.0"},"reference-count":63,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2015,3,2]],"date-time":"2015-03-02T00:00:00Z","timestamp":1425254400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Wallerian degeneration or nerve demyelination, arising from spinal nerve compression, is thought to bring on chronic neuropathic pain. The widely distributed metabotropic glutamate receptor subtype 5 (mGluR5) is involved in modulating nociceptive transmission. The purpose of this study was to investigate the potential effects of mGluR5 on peripheral hypersensitivities after chronic constriction injury (CCI). Sprague-Dawley rats were operated on with four loose ligatures around the sciatic nerve to induce thermal hyperalgesia and mechanical allodynia. Primary afferents in dermis after CCI exhibited progressive decreases, defined as partial cutaneous denervation; importantly, mGluR5 expressions in primary afferents were statistically increased. CCI-induced neuropathic pain behaviors through the intraplantar injections of 2-methyl-6-(phenylethynyl)-pyridine (MPEP), a selective mGluR5 antagonist, were dose-dependently attenuated. Furthermore, the most increased mGluR5 expressions in primary afferents surrounded by reactive Schwann cells were observed at the distal CCI stumps of sciatic nerves. In conclusion, these results suggest that nerve demyelination results in the increases of mGluR5 expression in injured primary afferents after CCI; and further suggest that mGluR5 represents a main therapeutic target in developing pharmacological strategies to prevent peripheral hypersensitivities.<\/jats:p>","DOI":"10.3390\/ijms16034642","type":"journal-article","created":{"date-parts":[[2015,3,2]],"date-time":"2015-03-02T10:45:12Z","timestamp":1425293112000},"page":"4642-4665","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Nerve Demyelination Increases Metabotropic Glutamate Receptor Subtype 5 Expression in Peripheral  Painful Mononeuropathy"],"prefix":"10.3390","volume":"16","author":[{"given":"Miau-Hwa","family":"Ko","sequence":"first","affiliation":[{"name":"Department of Anatomy, College of Medicine, China Medical University, Taichung 40402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6380-3455","authenticated-orcid":false,"given":"Yu-Lin","family":"Hsieh","sequence":"additional","affiliation":[{"name":"Department of Anatomy, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung-Tsang","family":"Hsieh","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, National Taiwan University College of Medicine,  Taipei 10051, Taiwan"},{"name":"Department of Neurology, National Taiwan University Hospital, Taipei 10002, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"To-Jung","family":"Tseng","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Institute of Medicine, Chung Shan Medical University,  Taichung 40201, Taiwan"},{"name":"Department of Medical Education, Chung Shan Medical University Hospital,  Taichung 40201, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2015,3,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7739","DOI":"10.1073\/pnas.96.14.7739","article-title":"Distinct neurochemical features of acute and persistent pain","volume":"96","author":"Basbaum","year":"1999","journal-title":"Proc. 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