Receptor mechanisms mediating the anti-neuroinflammatory effects of endocannabinoid system modulation in a rat model of migraine

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dc.authorid0000-0001-9261-2634en_US
dc.authorid0000-0003-3752-0846
dc.authorid0000-0001-7035-3336
dc.authorid0000-0002-1668-7850
dc.contributor.authorKılınç, Erkan
dc.contributor.authorAnkaralı, Seyit
dc.contributor.authorTorun, İbrahim Ethem
dc.contributor.authorDağıstan, Yaşar
dc.date.accessioned2021-06-23T19:17:10Z
dc.date.available2021-06-23T19:17:10Z
dc.date.issued2020
dc.departmentBAİBÜ, Tıp Fakültesi, Cerrahi Tıp Bilimleri Bölümüen_US
dc.departmentBAİBÜ, Tıp Fakültesi, Dahili Tıp Bilimleri Bölümü
dc.description.abstractCalcitonin gene-related peptide (CGRP), substance P and dural mast cells are main contributors in neurogenic inflammation underlying migraine pathophysiology. Modulation of endocannabinoid system attenuates migraine pain, but its mechanisms of action remain unclear. We investigated receptor mechanisms mediating anti-neuroinflammatory effects of endocannabinoid system modulation in in vivo migraine model and ex vivo hemiskull preparations in rats. To induce acute model of migraine, a single dose of nitroglycerin was intraperitoneally administered to male rats. Moreover, isolated ex vivo rat hemiskulls were prepared to study CGRP and substance P release from meningeal trigeminal afferents. We used methanandamide (cannabinoid agonist), rimonabant (cannabinoid receptor-1 CB1 antagonist), SR144528 (CB2 antagonist) and capsazepine (transient receptor potential vanilloid-1 TRPV1 antagonist) to explore effects of endocannabinoid system modulation on the neurogenic inflammation, and possible involvement of CB1, CB2 and TRPV1 receptors during endocannabinoid effects. Methanandamide attenuated nitroglycerin-induced CGRP increments in in vivo plasma, trigeminal ganglia and brainstem and also in ex vivo hemiskull preparations. Methanandamide also alleviated enhanced number and degranulation of dural mast cells induced by nitroglycerin. Rimonabant, but not capsazepine or SR144528, reversed the attenuating effects of methanandamide on CGRP release in both in vivo and ex vivo experiments. Additionally, SR144528, but not rimonabant or capsazepine, reversed the attenuating effects of methanandamide on dural mast cells. However, neither nitroglycerin nor methanandamide changed substance P levels in both in vivo and ex vivo experiments. Methanandamide modulates CGRP release in migraine-related structures via CB1 receptors and inhibits the degranulation of dural mast cells through CB2 receptors. Selective ligands targeting CB1 and CB2 receptors may provide novel and effective treatment strategies against migraine.en_US
dc.identifier.doi10.1111/ejn.14897
dc.identifier.endpage1031
dc.identifier.issn0953-816X
dc.identifier.issue4
dc.identifier.pmid32639078en_US
dc.identifier.scopus2-s2.0-85088387627en_US
dc.identifier.scopusqualityQ2en_US
dc.identifier.startpage1015
dc.identifier.urihttps://doi.org/10.1111/ejn.14897
dc.identifier.urihttps://hdl.handle.net/20.500.12491/5264
dc.identifier.volume55
dc.identifier.wosWOS:000552146800001en_US
dc.identifier.wosqualityQ3en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.institutionauthorKılınç, Erkan
dc.institutionauthorTorun, İbrahim Ethem
dc.institutionauthorDağıstan, Yaşar
dc.language.isoenen_US
dc.publisherWileyen_US
dc.relation.ispartofEuropean Journal Of Neuroscienceen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectCannabinoid Receptorsen_US
dc.subjectCGRPen_US
dc.subjectMast Cellsen_US
dc.subjectMethanandamideen_US
dc.subjectMigraineen_US
dc.subjectNeurogenic Inflammationen_US
dc.titleReceptor mechanisms mediating the anti-neuroinflammatory effects of endocannabinoid system modulation in a rat model of migraineen_US
dc.typeArticleen_US

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