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dc.contributor.authorThapa, Dinesh
dc.date.accessioned2019-11-28T16:39:49Z
dc.date.available2019-11-28T16:39:49Z
dc.identifier.urihttp://hdl.handle.net/10222/76707
dc.description.abstractThe endocannabinoid system, including cannabinoid 1 (CB1R) and cannabinoid 2 (CB2R) receptor, is an emerging target for treating pain and inflammation. This research investigated the effects of orthosteric and allosteric cannabinoid receptor ligands using a mouse model of corneal hyperalgesia. Behavioral pain responses were quantified 6 h after corneal chemical injury. Neutrophil infiltration was assessed by immunohistochemistry in post-mortem corneas 6-12 h post-injury. Tetrahydrocannabinol (∆8THC) mediated its anti-nociceptive and anti-inflammatory effects via CB1R whereas, cannabidiol (CBD) mediated anti-nociceptive and anti-inflammatory actions via 5-HT1A receptor. Anti-nociceptive and anti-inflammatory effects of the CBD-derivative, HU-308, were mediated via CB2R. Allosteric ligands can minimize side-effects associated with orthosteric receptor activation. The CB1R positive allosteric modulator (PAM), GAT229, and the ago-PAM, GAT211 (plus ∆8THC), or the CB1R allosteric agonist, GAT228, were anti-nociceptive and anti-inflammatory in cornea. Cannabinoids, together with allosteric ligands, could be a novel therapy for corneal pain and inflammation.en_US
dc.language.isoenen_US
dc.subjectCorneaen_US
dc.subjectPain and inflammationen_US
dc.subjectCannabinoidsen_US
dc.titleTARGETING THE ENDOCANNABINOID SYSTEM WITH ORTHOSTERIC AND ALLOSTERIC CANNABINOID LIGANDS TO REDUCE CORNEAL PAIN AND INFLAMMATIONen_US
dc.date.defence2018-01-08
dc.contributor.departmentDepartment of Pharmacologyen_US
dc.contributor.degreeMaster of Scienceen_US
dc.contributor.external-examinern/aen_US
dc.contributor.graduate-coordinatorDr. Ryan Pelisen_US
dc.contributor.thesis-readerDr. Eileen Denovan-Wrighten_US
dc.contributor.thesis-readerDr. Susan E. Howletten_US
dc.contributor.thesis-supervisorDr. Melanie Kellyen_US
dc.contributor.ethics-approvalReceiveden_US
dc.contributor.manuscriptsYesen_US
dc.contributor.copyright-releaseYesen_US
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