{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T09:14:15Z","timestamp":1783674855097,"version":"3.55.0"},"reference-count":64,"publisher":"Wiley","issue":"16","license":[{"start":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T00:00:00Z","timestamp":1778544000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T00:00:00Z","timestamp":1778544000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004099","name":"Ligue Contre le Cancer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004099","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>The G protein\u2010coupled estrogen receptor (GPER) participates in nociception. The GPER inverse agonist, a tetrapeptide (PLMI), was studied on pain\u2010like symptoms, in murine models of chemotherapy\u2010induced peripheral neuropathy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>All experiments were performed in mice. We used the PLMI and the GPER antagonist G15 to study the role of GPER in mechanical allodynia in the model of paclitaxel\u2010induced peripheral neuropathy. Sites of GPER\/PLMI actions were explored by using nociceptors and dorsal horn GPER knockouts. The effect of PLMI and\/or G15 was assessed in dorsal root ganglia primary cultures to explore the role of GPER in neuronal calcium flux. After a chronic administration of PLMI, the antinociceptive and neuroprotective effects were investigated in the paclitaxel\u2010induced neuropathy model. Short term memory, reward\u2010related conditioning and acute effects in bortezomib\u2010 and oxaliplatin\u2010induced nociception were evaluated. NMR and CD spectroscopy were used to determine the conformation of the peptide PLMI, in solution.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>In our paclitaxel\u2010induced pain\u2010like symptoms model, peripheral, spinal and supraspinal GPER participates in nociception. The peptide PLMI decreases nociception by lowering intraneuronal free calcium flux. Chronic PLMI treatment reduces pain\u2010like behaviours and protects against nerve conduction velocity deficits, without causing cognitive impairments or addiction. PLMI alleviates oxaliplatin\u2010 and bortezomib\u2010induced neuropathic pain. The peptide PLMI adopts a turn conformation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Implications<\/jats:title>\n                    <jats:p>Our results suggest that GPER inverse agonists could be used to alleviate nociception and to protect against paclitaxel\u2010induced peripheral neuropathy. The turn conformation of the PLMI peptide in solution is in favour of a bioactive GPCR\u2010interacting peptide.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70496","type":"journal-article","created":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T08:04:01Z","timestamp":1778573041000},"page":"4794-4817","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Antinociception and neuroprotection of the peptidic G protein\u2010coupled estrogen receptor inverse agonist PLMI in the murine model of paclitaxel\u2010induced peripheral neuropathy"],"prefix":"10.1111","volume":"183","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2135-8231","authenticated-orcid":false,"given":"Baptiste","family":"Jouffre","sequence":"first","affiliation":[{"name":"NEURO\u2010DOL, Pharmacologie Fondamentale et Clinique de la Douleur, INSERM \u2010 UMR 1107 Universit\u00e9 Clermont Auvergne  Clermont\u2010Ferrand 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