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CB2 cannabinoid receptor mediation of antinociception.
Pain. 2006 May; 122(1-2):36-42.PAIN

Abstract

Management of acute pain remains a significant clinical problem. In preclinical studies, CB2 cannabinoid receptor-selective agonists inhibit nociception without producing central nervous system side effects. The CB2 receptor-selective agonist AM1241 produces antinociceptive effects that are antagonized by CB2, but not CB1, receptor-selective antagonists, suggesting that activation of CB2 receptors results in antinociception. However, it has not been possible to definitively demonstrate that these effects are mediated by CB2 receptors, because we have lacked the pharmacological tools to confirm the in vivo receptor selectivity of the antagonists used. Further, recent evidence for cannabinoid-like receptors beyond CB1 and CB2 raises the possibility that AM1241 exerts its antinociceptive effects at uncharacterized CB2-like receptors that are also inhibited by AM630. The experiments reported here further test the hypothesis that CB2 receptor activation inhibits nociception. They evaluated the antinociceptive actions of AM1241 and the less-selective CB2 receptor agonist WIN55,212-2 in wild-type (CB2+/+) mice and in mice with genetic disruption of the CB2 receptor (CB2-/- mice). AM1241 inhibited thermal nociception in CB2+/+ mice, but had no effect in CB2-/- littermates. WIN55,212-2 produced equivalent antinociception in CB1+/+ and CB1-/- mice, while its antinociceptive effects were reduced in CB2-/- compared to CB2+/+ mice. The effects of morphine were not altered in CB2-/- compared to CB2+/+ mice. These data strongly suggest that AM1241 produces antinociception in vivo by activating CB2 cannabinoid receptors. Further, they confirm the potential therapeutic relevance of CB2 cannabinoid receptors for the treatment of acute pain.

Authors+Show Affiliations

The University of Arizona College of Medicine, Tucson, AZ, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

16563625

Citation

Ibrahim, Mohab M., et al. "CB2 Cannabinoid Receptor Mediation of Antinociception." Pain, vol. 122, no. 1-2, 2006, pp. 36-42.
Ibrahim MM, Rude ML, Stagg NJ, et al. CB2 cannabinoid receptor mediation of antinociception. Pain. 2006;122(1-2):36-42.
Ibrahim, M. M., Rude, M. L., Stagg, N. J., Mata, H. P., Lai, J., Vanderah, T. W., Porreca, F., Buckley, N. E., Makriyannis, A., & Malan, T. P. (2006). CB2 cannabinoid receptor mediation of antinociception. Pain, 122(1-2), 36-42.
Ibrahim MM, et al. CB2 Cannabinoid Receptor Mediation of Antinociception. Pain. 2006;122(1-2):36-42. PubMed PMID: 16563625.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - CB2 cannabinoid receptor mediation of antinociception. AU - Ibrahim,Mohab M, AU - Rude,Megan L, AU - Stagg,Nicola J, AU - Mata,Heriberto P, AU - Lai,Josephine, AU - Vanderah,Todd W, AU - Porreca,Frank, AU - Buckley,Nancy E, AU - Makriyannis,Alexandros, AU - Malan,T Philip,Jr Y1 - 2006/03/23/ PY - 2005/06/01/received PY - 2005/12/04/revised PY - 2005/12/19/accepted PY - 2006/3/28/pubmed PY - 2006/6/7/medline PY - 2006/3/28/entrez SP - 36 EP - 42 JF - Pain JO - Pain VL - 122 IS - 1-2 N2 - Management of acute pain remains a significant clinical problem. In preclinical studies, CB2 cannabinoid receptor-selective agonists inhibit nociception without producing central nervous system side effects. The CB2 receptor-selective agonist AM1241 produces antinociceptive effects that are antagonized by CB2, but not CB1, receptor-selective antagonists, suggesting that activation of CB2 receptors results in antinociception. However, it has not been possible to definitively demonstrate that these effects are mediated by CB2 receptors, because we have lacked the pharmacological tools to confirm the in vivo receptor selectivity of the antagonists used. Further, recent evidence for cannabinoid-like receptors beyond CB1 and CB2 raises the possibility that AM1241 exerts its antinociceptive effects at uncharacterized CB2-like receptors that are also inhibited by AM630. The experiments reported here further test the hypothesis that CB2 receptor activation inhibits nociception. They evaluated the antinociceptive actions of AM1241 and the less-selective CB2 receptor agonist WIN55,212-2 in wild-type (CB2+/+) mice and in mice with genetic disruption of the CB2 receptor (CB2-/- mice). AM1241 inhibited thermal nociception in CB2+/+ mice, but had no effect in CB2-/- littermates. WIN55,212-2 produced equivalent antinociception in CB1+/+ and CB1-/- mice, while its antinociceptive effects were reduced in CB2-/- compared to CB2+/+ mice. The effects of morphine were not altered in CB2-/- compared to CB2+/+ mice. These data strongly suggest that AM1241 produces antinociception in vivo by activating CB2 cannabinoid receptors. Further, they confirm the potential therapeutic relevance of CB2 cannabinoid receptors for the treatment of acute pain. SN - 1872-6623 UR - https://www.unboundmedicine.com/medline/citation/16563625/CB2_cannabinoid_receptor_mediation_of_antinociception_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0304-3959(05)00640-8 DB - PRIME DP - Unbound Medicine ER -