Selective activation of cannabinoid CB2 receptors suppresses hyperalgesia evoked by intradermal capsaicin - PubMed (original) (raw)
. 2004 Feb;308(2):446-53.
doi: 10.1124/jpet.103.060079. Epub 2003 Nov 10.
Affiliations
- PMID: 14610224
- DOI: 10.1124/jpet.103.060079
Selective activation of cannabinoid CB2 receptors suppresses hyperalgesia evoked by intradermal capsaicin
Andrea G Hohmann et al. J Pharmacol Exp Ther. 2004 Feb.
Abstract
The present studies were conducted to test the hypothesis that activation of peripheral cannabinoid CB(2) receptors would suppress hyperalgesia evoked by intradermal administration of capsaicin, the pungent ingredient in hot chili peppers. The CB(2)-selective cannabinoid agonist (2-iodo-5-nitro-phenyl)-[1-(1-methyl-piperidin-2-ylmethyl)-1H-indol-3-yl]-methanone (AM1241) (33, 330 microg/kg i.p.) suppressed the development of capsaicin-evoked thermal and mechanical hyperalgesia and allodynia. AM1241 also produced a dose-dependent suppression of capsaicin-evoked nocifensive behavior. The AM1241-induced suppression of each parameter of capsaicin-evoked pain behavior was completely blocked by the CB(2) antagonist N-[(1S)-endo-1,3,3-trimethyl bicycle [2.2.1] heptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyrazole-3-carboxamide (SR144528) but not by the CB(1) antagonist N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamidehydrochloride (SR141716A). AM1241 (33 microg/kg i.pl.) suppressed capsaicin-evoked thermal and mechanical hyperalgesia and allodynia after local administration to the capsaicin-treated (ipsilateral) paw but was inactive after administration to the capsaicin-untreated (contralateral) paw. Our data indicate that AM1241 suppresses capsaicin-evoked hyperalgesia and allodynia through a local site of action. These data provide evidence that actions at cannabinoid CB(2) receptors are sufficient to normalize nociceptive thresholds and produce antinociception in persistent pain states.
Similar articles
- Activation of peripheral cannabinoid CB1 and CB2 receptors suppresses the maintenance of inflammatory nociception: a comparative analysis.
Gutierrez T, Farthing JN, Zvonok AM, Makriyannis A, Hohmann AG. Gutierrez T, et al. Br J Pharmacol. 2007 Jan;150(2):153-63. doi: 10.1038/sj.bjp.0706984. Epub 2006 Dec 11. Br J Pharmacol. 2007. PMID: 17160008 Free PMC article. - Selective activation of cannabinoid CB(2) receptors suppresses spinal fos protein expression and pain behavior in a rat model of inflammation.
Nackley AG, Makriyannis A, Hohmann AG. Nackley AG, et al. Neuroscience. 2003;119(3):747-57. doi: 10.1016/s0306-4522(03)00126-x. Neuroscience. 2003. PMID: 12809695 - Selective activation of cannabinoid CB2 receptors suppresses neuropathic nociception induced by treatment with the chemotherapeutic agent paclitaxel in rats.
Rahn EJ, Zvonok AM, Thakur GA, Khanolkar AD, Makriyannis A, Hohmann AG. Rahn EJ, et al. J Pharmacol Exp Ther. 2008 Nov;327(2):584-91. doi: 10.1124/jpet.108.141994. Epub 2008 Jul 29. J Pharmacol Exp Ther. 2008. PMID: 18664590 Free PMC article. - Inhibition of pain responses by activation of CB(2) cannabinoid receptors.
Malan TP Jr, Ibrahim MM, Vanderah TW, Makriyannis A, Porreca F. Malan TP Jr, et al. Chem Phys Lipids. 2002 Dec 31;121(1-2):191-200. doi: 10.1016/s0009-3084(02)00155-x. Chem Phys Lipids. 2002. PMID: 12505700 Review. - Cannabinoid CB2 receptor-mediated anti-nociception in models of acute and chronic pain.
Jhaveri MD, Sagar DR, Elmes SJ, Kendall DA, Chapman V. Jhaveri MD, et al. Mol Neurobiol. 2007 Aug;36(1):26-35. doi: 10.1007/s12035-007-8007-7. Epub 2007 Oct 2. Mol Neurobiol. 2007. PMID: 17952647 Review.
Cited by
- Targeting the endocannabinoid system: a predictive, preventive, and personalized medicine-directed approach to the management of brain pathologies.
Reddy V, Grogan D, Ahluwalia M, Salles ÉL, Ahluwalia P, Khodadadi H, Alverson K, Nguyen A, Raju SP, Gaur P, Braun M, Vale FL, Costigliola V, Dhandapani K, Baban B, Vaibhav K. Reddy V, et al. EPMA J. 2020 Apr 15;11(2):217-250. doi: 10.1007/s13167-020-00203-4. eCollection 2020 Jun. EPMA J. 2020. PMID: 32549916 Free PMC article. Review. - Role of cannabinoids in the treatment of pain and (painful) spasticity.
Karst M, Wippermann S, Ahrens J. Karst M, et al. Drugs. 2010 Dec 24;70(18):2409-38. doi: 10.2165/11585260-000000000-00000. Drugs. 2010. PMID: 21142261 Review. - Crystal structure of a soluble form of human monoglyceride lipase in complex with an inhibitor at 1.35 Å resolution.
Schalk-Hihi C, Schubert C, Alexander R, Bayoumy S, Clemente JC, Deckman I, DesJarlais RL, Dzordzorme KC, Flores CM, Grasberger B, Kranz JK, Lewandowski F, Liu L, Ma H, Maguire D, Macielag MJ, McDonnell ME, Mezzasalma Haarlander T, Miller R, Milligan C, Reynolds C, Kuo LC. Schalk-Hihi C, et al. Protein Sci. 2011 Apr;20(4):670-83. doi: 10.1002/pro.596. Epub 2011 Mar 1. Protein Sci. 2011. PMID: 21308848 Free PMC article. - Contributions of academic laboratories to the discovery and development of chemical biology tools.
Huryn DM, Resnick LO, Wipf P. Huryn DM, et al. J Med Chem. 2013 Sep 26;56(18):7161-76. doi: 10.1021/jm400132d. Epub 2013 May 31. J Med Chem. 2013. PMID: 23672690 Free PMC article. Review. - In vitro pharmacological characterization of AM1241: a protean agonist at the cannabinoid CB2 receptor?
Yao BB, Mukherjee S, Fan Y, Garrison TR, Daza AV, Grayson GK, Hooker BA, Dart MJ, Sullivan JP, Meyer MD. Yao BB, et al. Br J Pharmacol. 2006 Sep;149(2):145-54. doi: 10.1038/sj.bjp.0706838. Epub 2006 Aug 7. Br J Pharmacol. 2006. PMID: 16894349 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical