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The antinociceptive effects of intraplantar injections of 2-arachidonoyl glycerol are mediated by cannabinoid CB2 receptors.
Br J Pharmacol. 2007 Mar; 150(6):693-701.BJ

Abstract

BACKGROUND AND PURPOSE

2-arachidonoyl glycerol (2-AG) is an endogenous cannabinoid with central antinociceptive properties. Its degradation is catalysed by monoacylglycerol lipase (MGL) whose activity is inhibited by URB602, a new synthetic compound. The peripheral antinociceptive effects of 2-AG and URB602 in an inflammatory model of pain are not yet determined. We have evaluated these effects with and without the cannabinoid CB(1) (AM251) and CB(2) (AM630) receptor antagonists.

EXPERIMENTAL APPROACH

Inflammation was induced in rat hind paws by intraplantar injection of formalin. Nociception was assessed behaviourally over the next 60 min, in 19 experimental groups: (1) control; (2-6) 2-AG (0.01-100 microg); (7) AM251 (80 microg); (8) AM251+2-AG (10 microg); (9) AM630 (25 microg); (10) AM630+2-AG (10 microg); (11-16) URB602 (0.1-500 microg); (17) 2-AG+URB602 (ED(50)); (18) AM251+URB602 (ED(50)); (19) AM630+URB602 (ED(50)). Drugs were injected s.c. in the dorsal surface of the hind paw (50 microl), 15 min before formalin injection into the same paw.

KEY RESULTS

2-AG and URB602 produced dose-dependent antinociceptive effects for the late phases of the formalin test with ED(50) of 0.65+/-0.455 mug and 68+/-14.3 microg, respectively. Their combination at ED(50) doses produced an additive antinociceptive effect. These effects were inhibited by AM630 but not by AM251 for 2-AG and by the two cannabinoid antagonists for URB602.

CONCLUSIONS AND IMPLICATIONS

Locally injected 2-AG and URB602 decreased pain behaviour in a dose-dependent manner in an inflammatory model of pain. The antinociceptive effect of 2-AG was mediated by the CB(2) receptor.

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Authors+Show Affiliations

Guindon J
Department of Pharmacology, Faculty of Medicine, Université de Montréal, Québec, Canada.
Desroches J
No affiliation info available
Beaulieu P
No affiliation info available

MeSH

Analgesics, Non-NarcoticAnimalsArachidonic AcidsBiphenyl CompoundsDose-Response Relationship, DrugEndocannabinoidsEnzyme InhibitorsGlyceridesIndolesMaleMonoacylglycerol LipasesPain MeasurementPiperidinesPyrazolesRatsRats, WistarReceptor, Cannabinoid, CB1Receptor, Cannabinoid, CB2

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17179944

Citation

Guindon, J, et al. "The Antinociceptive Effects of Intraplantar Injections of 2-arachidonoyl Glycerol Are Mediated By Cannabinoid CB2 Receptors." British Journal of Pharmacology, vol. 150, no. 6, 2007, pp. 693-701.
Guindon J, Desroches J, Beaulieu P. The antinociceptive effects of intraplantar injections of 2-arachidonoyl glycerol are mediated by cannabinoid CB2 receptors. Br J Pharmacol. 2007;150(6):693-701.
Guindon, J., Desroches, J., & Beaulieu, P. (2007). The antinociceptive effects of intraplantar injections of 2-arachidonoyl glycerol are mediated by cannabinoid CB2 receptors. British Journal of Pharmacology, 150(6), 693-701.
Guindon J, Desroches J, Beaulieu P. The Antinociceptive Effects of Intraplantar Injections of 2-arachidonoyl Glycerol Are Mediated By Cannabinoid CB2 Receptors. Br J Pharmacol. 2007;150(6):693-701. PubMed PMID: 17179944.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The antinociceptive effects of intraplantar injections of 2-arachidonoyl glycerol are mediated by cannabinoid CB2 receptors. AU - Guindon,J, AU - Desroches,J, AU - Beaulieu,P, Y1 - 2006/12/18/ PY - 2006/12/21/pubmed PY - 2007/5/4/medline PY - 2006/12/21/entrez SP - 693 EP - 701 JF - British journal of pharmacology JO - Br J Pharmacol VL - 150 IS - 6 N2 - BACKGROUND AND PURPOSE: 2-arachidonoyl glycerol (2-AG) is an endogenous cannabinoid with central antinociceptive properties. Its degradation is catalysed by monoacylglycerol lipase (MGL) whose activity is inhibited by URB602, a new synthetic compound. The peripheral antinociceptive effects of 2-AG and URB602 in an inflammatory model of pain are not yet determined. We have evaluated these effects with and without the cannabinoid CB(1) (AM251) and CB(2) (AM630) receptor antagonists. EXPERIMENTAL APPROACH: Inflammation was induced in rat hind paws by intraplantar injection of formalin. Nociception was assessed behaviourally over the next 60 min, in 19 experimental groups: (1) control; (2-6) 2-AG (0.01-100 microg); (7) AM251 (80 microg); (8) AM251+2-AG (10 microg); (9) AM630 (25 microg); (10) AM630+2-AG (10 microg); (11-16) URB602 (0.1-500 microg); (17) 2-AG+URB602 (ED(50)); (18) AM251+URB602 (ED(50)); (19) AM630+URB602 (ED(50)). Drugs were injected s.c. in the dorsal surface of the hind paw (50 microl), 15 min before formalin injection into the same paw. KEY RESULTS: 2-AG and URB602 produced dose-dependent antinociceptive effects for the late phases of the formalin test with ED(50) of 0.65+/-0.455 mug and 68+/-14.3 microg, respectively. Their combination at ED(50) doses produced an additive antinociceptive effect. These effects were inhibited by AM630 but not by AM251 for 2-AG and by the two cannabinoid antagonists for URB602. CONCLUSIONS AND IMPLICATIONS: Locally injected 2-AG and URB602 decreased pain behaviour in a dose-dependent manner in an inflammatory model of pain. The antinociceptive effect of 2-AG was mediated by the CB(2) receptor. SN - 0007-1188 UR - https://www.unboundmedicine.com/medline/citation/17179944/The_antinociceptive_effects_of_intraplantar_injections_of_2_arachidonoyl_glycerol_are_mediated_by_cannabinoid_CB2_receptors_ L2 - https://doi.org/10.1038/sj.bjp.0706990 DB - PRIME DP - Unbound Medicine ER -