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However, despite current preclinical evidence supporting the use of CB<jats:sub>2<\/jats:sub> agonists for pain, successful translation of findings from preclinical models to human patients is lacking. This gap may reflect an incomplete understanding of the types of pain that best respond to CB<jats:sub>2<\/jats:sub> receptor activation, as well as limited knowledge of mechanisms underlying CB<jats:sub>2<\/jats:sub>\u2010mediated attenuation of pain behaviours. Additionally, how ligand\u2010specific biased signalling impacts CB<jats:sub>2<\/jats:sub>\u2010mediated analgesia in various types of pain has not been well characterized. Here, we review the preclinical literature that has examined the potential therapeutic efficacy of CB<jats:sub>2<\/jats:sub> agonists in rodent pain models associated with inflammation, traumatic nerve injury, toxic neuropathy (e.g. due to chemotherapy and anti\u2010retroviral treatment), post\u2010surgical pain, visceral pain and disease\u2010associated (e.g. due to cancer, arthritis and diabetes) pain states. We also discuss what is currently known about the mechanisms underlying these effects with an emphasis on insights derived from recently developed CB<jats:sub>2<\/jats:sub> reporter mice and conditional knockout (cKO) mouse models. These tools compensate for limitations of functional (rather than complete) global knockout (KO) mouse lines and lack of specificity of available CB<jats:sub>2<\/jats:sub> receptor antibodies to provide a more comprehensive understanding of CB<jats:sub>2<\/jats:sub>\u2010mediated analgesic mechanisms.<\/jats:p>","DOI":"10.1111\/bph.70116","type":"journal-article","created":{"date-parts":[[2025,7,4]],"date-time":"2025-07-04T03:13:38Z","timestamp":1751598818000},"page":"5090-5118","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Cannabinoid CB<sub>2<\/sub> receptor\u2010mediated analgesia: mechanism\u2010based insights and therapeutic potential"],"prefix":"10.1111","volume":"182","author":[{"given":"Kelsey G.","family":"Guenther","sequence":"first","affiliation":[{"name":"Program in Neuroscience Indiana University Bloomington  Bloomington Indiana USA"},{"name":"Department of Psychological and Brain Sciences Indiana 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