{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T10:06:23Z","timestamp":1784887583651,"version":"3.55.0"},"reference-count":57,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2020,1,20]],"date-time":"2020-01-20T00:00:00Z","timestamp":1579478400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["MOP-97768"],"award-info":[{"award-number":["MOP-97768"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["EY024717, EY024625"],"award-info":[{"award-number":["EY024717, EY024625"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Cannabinoid receptor 1 (CB1) activation has been reported to reduce transient receptor potential cation channel subfamily V member 1 (TRPV1)-induced inflammatory responses and is anti-nociceptive and anti-inflammatory in corneal injury. We examined whether allosteric ligands, can modulate CB1 signaling to reduce pain and inflammation in corneal hyperalgesia. Corneal hyperalgesia was generated by chemical cauterization of cornea in wildtype and CB2 knockout (CB2\u2212\/\u2212) mice. The novel racemic CB1 allosteric ligand GAT211 and its enantiomers GAT228 and GAT229 were examined alone or in combination with the orthosteric CB1 agonist \u03948-tetrahydrocannabinol (\u03948-THC). Pain responses were assessed following capsaicin (1 \u00b5M) stimulation of injured corneas at 6 h post-cauterization. Corneal neutrophil infiltration was also analyzed. GAT228, but not GAT229 or GAT211, reduced pain scores in response to capsaicin stimulation. Combination treatments of 0.5% GAT229 or 1% GAT211 with subthreshold \u03948-THC (0.4%) significantly reduced pain scores following capsaicin stimulation. The anti-nociceptive effects of both GAT229 and GAT228 were blocked with CB1 antagonist AM251, but remained unaffected in CB2\u2212\/\u2212 mice. Two percent GAT228, or the combination of 0.2% \u03948-THC with 0.5% GAT229 also significantly reduced corneal inflammation. CB1 allosteric ligands could offer a novel approach for treating corneal pain and inflammation.<\/jats:p>","DOI":"10.3390\/molecules25020417","type":"journal-article","created":{"date-parts":[[2020,1,21]],"date-time":"2020-01-21T03:04:43Z","timestamp":1579575883000},"page":"417","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Allosteric Cannabinoid Receptor 1 (CB1) Ligands Reduce Ocular Pain and Inflammation"],"prefix":"10.3390","volume":"25","author":[{"given":"Dinesh","family":"Thapa","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Dalhousie University, Halifax, NS B3H 4R2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9816-4761","authenticated-orcid":false,"given":"Elizabeth A.","family":"Cairns","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Dalhousie University, Halifax, NS B3H 4R2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna-Maria","family":"Szczesniak","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Dalhousie University, Halifax, NS B3H 4R2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pushkar M.","family":"Kulkarni","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Northeastern University, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex J.","family":"Straiker","sequence":"additional","affiliation":[{"name":"Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN 47405, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ganesh A.","family":"Thakur","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Northeastern University, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie E. M.","family":"Kelly","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Dalhousie University, Halifax, NS B3H 4R2, Canada"},{"name":"Department of Anesthesia, Pain Management &amp; Perioperative Medicine, Dalhousie University, Halifax, NS B3H 4R2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,1,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/S1542-0124(12)70112-X","article-title":"Nerves and sensations from the eye surface","volume":"2","author":"Belmonte","year":"2004","journal-title":"Ocul. Surf."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/S0014-4835(03)00050-2","article-title":"Corneal nerves: Structure, contents and function","volume":"76","author":"Marfurt","year":"2003","journal-title":"Exp. 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