dc.contributor.author | Thapa, Dinesh | |
dc.date.accessioned | 2019-11-28T16:39:49Z | |
dc.date.available | 2019-11-28T16:39:49Z | |
dc.date.issued | 2019-11-28T16:39:49Z | |
dc.identifier.uri | http://hdl.handle.net/10222/76707 | |
dc.description.abstract | The 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.iso | en | en_US |
dc.subject | Cornea | en_US |
dc.subject | Pain and inflammation | en_US |
dc.subject | Cannabinoids | en_US |
dc.title | TARGETING THE ENDOCANNABINOID SYSTEM WITH ORTHOSTERIC AND ALLOSTERIC CANNABINOID LIGANDS TO REDUCE CORNEAL PAIN AND INFLAMMATION | en_US |
dc.date.defence | 2018-01-08 | |
dc.contributor.department | Department of Pharmacology | en_US |
dc.contributor.degree | Master of Science | en_US |
dc.contributor.external-examiner | n/a | en_US |
dc.contributor.graduate-coordinator | Dr. Ryan Pelis | en_US |
dc.contributor.thesis-reader | Dr. Eileen Denovan-Wright | en_US |
dc.contributor.thesis-reader | Dr. Susan E. Howlett | en_US |
dc.contributor.thesis-supervisor | Dr. Melanie Kelly | en_US |
dc.contributor.ethics-approval | Received | en_US |
dc.contributor.manuscripts | Yes | en_US |
dc.contributor.copyright-release | Yes | en_US |