{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T09:01:35Z","timestamp":1785142895087,"version":"3.55.0"},"reference-count":38,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T00:00:00Z","timestamp":1783036800000},"content-version":"vor","delay-in-days":32,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["310467\/2023\u20103"],"award-info":[{"award-number":["310467\/2023\u20103"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Archiv der Pharmazie"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Although first\u2010line pharmacological treatments for neuropathic pain are often ineffective, cannabidiol has shown promise. However, the analgesic effects of orally administered, cannabidiol are limited by low bioavailability and a short half\u2010life. Therefore, this study investigated the effects of intrathecal (i.t.), cannabidiol administration on neuropathic pain, focusing on spinal 5\u2010HT\n                    <jats:sub>1A<\/jats:sub>\n                    receptors and microglial modulation. Male C57BL\/6 mice were subjected to neuropathic pain\u2010induced by chronic constriction injury (CCI). Mechanical nociceptive thresholds were assessed using von Frey filaments. The involvement of spinal 5\u2010HT\n                    <jats:sub>1A<\/jats:sub>\n                    receptors was examined by i.t. administration of the selective antagonist WAY\u2010100635. mRNA expression, IL\u201010, and TNF\u2010\u03b1 levels, and microglial activation were evaluated. Intrathecal, cannabidiol significantly reversed mechanical allodynia, producing a more potent and prolonged antinociceptive effect than oral administration. This effect was abolished by WAY\u2010100635, indicating spinal 5\u2010HT\n                    <jats:sub>1A<\/jats:sub>\n                    receptor involvement. Moreover, i.t. cannabidiol increased spinal IL\u201010 levels and 5\u2010HT\n                    <jats:sub>1A<\/jats:sub>\n                    receptor mRNA expression, while reducing microglial activation. In vitro, cannabidiol attenuated microglial activation and significantly reduced TNF\u2010\u03b1 production. In conclusion, i.t. cannabidiol effectively alleviates neuropathic pain in mice, with findings that may suggest the involvement of spinal mechanisms associated with 5\u2010HT\n                    <jats:sub>1A<\/jats:sub>\n                    receptor\u2010related signaling and modulation of microglial activation.\n                  <\/jats:p>","DOI":"10.1002\/ardp.70282","type":"journal-article","created":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T12:00:15Z","timestamp":1783080015000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Spinal 5\u2010HT\n                    <sub>1A<\/sub>\n                    Receptor\u2010Related and Microglial Mechanisms Associated With Intrathecal Cannabidiol\u2010Induced Antinociception in Neuropathic Pain"],"prefix":"10.1002","volume":"359","author":[{"given":"Sergio Saboia","family":"Junior","sequence":"first","affiliation":[{"name":"Laboratory of Neuroimmunobiology of Pain, Center for Experimental Biology Federal University of Alfenas  Alfenas Minas Gerais Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafaela Silva dos","family":"Santos","sequence":"additional","affiliation":[{"name":"Laboratory of Neuroimmunobiology of Pain, Center for Experimental Biology Federal University of Alfenas  Alfenas Minas Gerais Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00edvia Maria Ribeiro","family":"Ros\u00e1rio","sequence":"additional","affiliation":[{"name":"Laboratory of Neuroimmunobiology of Pain, Center for Experimental Biology Federal University of Alfenas  Alfenas Minas Gerais Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rayner Ribeiro","family":"Cardoso","sequence":"additional","affiliation":[{"name":"Laboratory of Neuroimmunobiology of Pain, Center for Experimental Biology Federal University of Alfenas  Alfenas Minas Gerais Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fl\u00e1vio Protasio","family":"Veras","sequence":"additional","affiliation":[{"name":"Laboratory of Neuroimmunobiology of Pain, Center for Experimental Biology Federal University of Alfenas  Alfenas Minas Gerais Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00e3o Paulo","family":"Prado","sequence":"additional","affiliation":[{"name":"Laboratory of Neuroimmunobiology of Pain, Center for Experimental Biology Federal University of Alfenas  Alfenas Minas Gerais Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ester Siqueira Caixeita","family":"Nogueira","sequence":"additional","affiliation":[{"name":"Department of Cellular and Developmental Biology Federal University of Alfenas  Alfenas Minas Gerais State Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angel Roberto","family":"Barchuk","sequence":"additional","affiliation":[{"name":"Insect Molecular Biology Laboratory Federal University of Alfenas  Alfenas Minas Gerais Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thiago Roberto Lima","family":"Romero","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Laboratory of Pain and Analgesia Federal University of Minas Gerais  Belo Horizonte Minas Gerais Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovane","family":"Galdino","sequence":"additional","affiliation":[{"name":"Laboratory of Neuroimmunobiology of Pain, Center for Experimental Biology Federal University of Alfenas  Alfenas Minas Gerais 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