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The underlying mechanism, however, remains unclear. The present study was, therefore, designed to determine the roles of peripheral group III metabotropic glutamate receptors (mGluRs) in formalin\u2010evoked spontaneous nociception. Pre\u2010treatment with intraplantar injections of L\u2010serine\u2010O\u2010phosphate (L\u2010SOP), a group III mGluRs agonist, significantly inhibited formalin\u2010induced nociceptive behaviours and decreased Fos production in the spinal dorsal horn. The inhibitory effects of L\u2010SOP were abolished completely by pre\u2010treatment with the group III mGluR antagonist (RS)\u2010a\u2010methylserine\u2010O\u2010phosphate (M\u2010SOP). These data suggest that the activation of group III mGluRs in the periphery may play a differential role in formalin\u2010induced nociception. In addition, L\u2010SOP decreased the formalin\u2010induced upregulation of tumour necrosis factor\u2010\u03b1 (TNF\u2010\u03b1) as well as interleukine\u20101\u03b2 (IL\u20101\u03b2) expression in the spinal cord, suggesting that activation of peripheral group III mGluRs reduces formalin\u2010induced nociception through inhibition of the pro\u2010inflammatory cytokines in the spinal cord. Therefore, the agonists acting peripheral group III mGluRs possess therapeutic effectiveness in chronic pain.<\/jats:p>","DOI":"10.1111\/1440-1681.13602","type":"journal-article","created":{"date-parts":[[2021,10,19]],"date-time":"2021-10-19T13:52:35Z","timestamp":1634651555000},"page":"319-326","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Activation of peripheral group III metabotropic glutamate receptors suppressed formalin\u2010induced nociception"],"prefix":"10.1111","volume":"49","author":[{"given":"Yan\u2010Li","family":"Li","sequence":"first","affiliation":[{"name":"Department of Neurology First Hospital, Shanxi Medical University Taiyuan Shanxi P.R.China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin\u2010Rui","family":"Chang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Cellular Physiology at Shanxi Medical University Ministry of Education Key Laboratory of 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