Activation of CB1 and CB2 receptors attenuates the induction and maintenance of inflammatory pain in the rat
Abstract
The aim of the present study was to investigate the effects of cannabinoid agonists on established inflammatory hyperalgesia. We have compared the effects of pre-administration versus post-administration of a potent non-selective cannabinoid agonist HU210 and a selective CB2 receptor agonist JWH-133 on hindpaw weight bearing and paw oedema in the carrageenan model of inflammatory hyperalgesia. For comparative purposes we also determined the effects of the mu-opioid receptor agonist morphine and the COX2 inhibitor rofecoxib in this model. At 3 h following intraplantar injection of carrageenan (2%, 100 microl) there was a significant (P < 0.001) reduction in weight bearing on the ipsilateral hindpaw, compared to vehicle treated rats and a concomitant increase in ipsilateral hindpaw volume (P < 0.001), compared to vehicle treated rats. Systemic administration of HU210 (10 microg/kg) and JWH-133 (10 mg/kg) at 3 h following injection of carrageenan, significantly attenuated decreases in ipsilateral hindpaw weight bearing (P < 0.05 for both) and paw volume (P < 0.001 for both). Pre-administration of HU210 and JWH-133 had similar effects on weight bearing in this model. Pre-administered HU210 also significantly decreased carrageenan-induced changes in paw volume (P < 0.001), this was not the case for JWH-133. Effects of post-administered HU210 and JWH-133 on ipsilateral hindpaw weight bearing and paw volume were comparable to the effect of systemic post-administration of morphine and rofecoxib (3 mg/kg for both). In summary, both HU210 and JWH-133 attenuated established inflammatory hypersensitivity and swelling, suggesting that cannabinoid-based drugs have clinical potential for the treatment of established inflammatory pain responses.
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The synthetic cannabinoid agonist HU-210 restores the carrageenan-induced reduction in weight bearing in rats.
“For example, the synthetic cannabinoid agonist HU-210 restores the carrageenan-induced reduction in weight bearing in rats (Clayton et al, 2002;Elmes et al, 2005;Sofia et al, 1973).”
From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Elmes et al, 2005
The selective CB2 receptor agonists GW405833 and JWH133 attenuate edema and restore weight bearing in rat paws injected with carrageenan.
“The selective CB 2 receptor agonists GW405833 and JWH133 attenuate edema and restore weight bearing in rat paws injected with carrageenan (Clayton et al, 2002;Elmes et al, 2005).”
From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Elmes et al, 2005
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- Authors
- Elmes, S. J. R., Winyard, L. A., Medhurst, S. J., Clayton, N. M., Wilson, A. W., Kendall, D. A., & Chapman, V.
- Affiliations
- University of Nottingham (GB)
- GlaxoSmithKline (United Kingdom) (GB)
- Corresponding author
- Chapman, Victoria
- Venue
- Pain
- Published
- 2005-12
- Volume
- 118
- Issue
- 3
- Pages
- 327-335
- ISSN
- 0304-3959 (ISSN-L)
- OpenAlex
- W2080086221
- Cited by
- 97
- References
- 33
- Citations by year
- 2025: 2 · 2024: 3 · 2023: 5 · 2022: 1 · 2021: 6 · 2020: 6 · 2019: 2 · 2018: 5 · 2017: 3 · 2016: 4 · 2015: 1 · 2014: 3 · 2013: 4 · 2012: 4
- FWCI
- 7.02
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Pain (publishedVersion)
- PubMed (publishedVersion)
- Funders
- GlaxoSmithKline
- University of Nottingham
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Health Sciences › Medicine › Pharmacology › Inflammatory mediators and NSAID effects
- Keywords
- cannabinoid receptors, CB1 receptor, CB2 receptor, HU-210, JWH-133, inflammatory hyperalgesia, inflammatory pain, carrageenan-induced paw edema, mu-opioid receptor, morphine, rofecoxib, COX-2 inhibition, cannabinoid receptor agonists
- MeSH terms
- Analgesics, Animals, Cannabinoids, Carrageenan, Drug Combinations, Hyperalgesia, Inflammation, Male, Dronabinol, Weight-Bearing, Treatment Outcome, Receptor, Cannabinoid, CB1, Receptor, Cannabinoid, CB2, Rats
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