{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T15:27:38Z","timestamp":1791473258800,"version":"4.3.4"},"reference-count":232,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2022,8,21]],"date-time":"2022-08-21T00:00:00Z","timestamp":1661040000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health (NIH)","doi-asserted-by":"publisher","award":["R01 NS038261"],"award-info":[{"award-number":["R01 NS038261"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Metabotropic glutamate receptors (mGluR or mGlu) are G-protein coupled receptors activated by the binding of glutamate, the main classical neurotransmitter of the nervous system. Eight different mGluR subtypes (mGluR1-8) have been cloned and are classified in three groups based on their molecular, pharmacological and signaling properties. mGluRs mediate several physiological functions such as neuronal excitability and synaptic plasticity, but they have also been implicated in numerous pathological conditions including pain. The availability of new and more selective allosteric modulators together with the canonical orthosteric ligands and transgenic technologies has led to significant advances in our knowledge about the role of the specific mGluR subtypes in the pathophysiological mechanisms of various diseases. Although development of successful compounds acting on mGluRs for clinical use has been scarce, the subtype-specific-pharmacological manipulation might be a compelling approach for the treatment of several disorders in humans, including pain; this review aims to summarize and update on preclinical evidence for the roles of different mGluRs in the pain system and discusses knowledge gaps regarding mGluR-related sex differences and neuroimmune signaling in pain.<\/jats:p>","DOI":"10.3390\/cells11162608","type":"journal-article","created":{"date-parts":[[2022,8,21]],"date-time":"2022-08-21T21:05:51Z","timestamp":1661115951000},"page":"2608","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Recent Advances in the Modulation of Pain by the Metabotropic Glutamate Receptors"],"prefix":"10.3390","volume":"11","author":[{"given":"Mariacristina","family":"Mazzitelli","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Neuroscience, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peyton","family":"Presto","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Neuroscience, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nico","family":"Antenucci","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Neuroscience, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shakira","family":"Meltan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Neuroscience, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Volker","family":"Neugebauer","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Neuroscience, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA"},{"name":"Center of Excellence for Translational Neuroscience and Therapeutics, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA"},{"name":"Garrison Institute on Aging, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e273","DOI":"10.1016\/j.bja.2019.03.023","article-title":"Chronic pain: A review of its epidemiology and associated factors in population-based studies","volume":"123","author":"Mills","year":"2019","journal-title":"Br. 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