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The antinociceptive effect of Delta9-tetrahydrocannabinol in the arthritic rat involves the CB(2) cannabinoid receptor.
Eur J Pharmacol 2007; 570(1-3):50-6EJ

Abstract

Cannabinoid CB(2) receptors have been implicated in antinociception in animal models of both acute and chronic pain. We evaluated the role both cannabinoid CB(1) and CB(2) receptors in mechanonociception in non-arthritic and arthritic rats. The antinociceptive effect of Delta(9)-tetrahydrocannabinol (Delta(9)THC) was determined in rats following administration of the cannabinoid CB(1) receptor-selective antagonist, SR141716A, the cannabinoid CB(2) receptor-selective antagonist, SR144528, or vehicle. Male Sprague-Dawley rats were rendered arthritic using Freund's complete adjuvant and tested for mechanical hyperalgesia in the paw-pressure test. Arthritic rats had a baseline paw-pressure of 83 +/- 3.6 g versus a paw-pressure of 177 +/- 6.42 g in non-arthritic rats. SR144528 or SR141716A (various doses mg/kg; i.p.) or 1:1:18 (ethanol:emulphor:saline) vehicle were injected 1 h prior to Delta(9)THC (4 mg/kg; i.p) or 1:1:18 vehicle and antinociception determined 30min post Delta(9)THC. AD(50)'s for both antagonists were calculated with 95% confidence limits. In addition, midbrain and spinal cord were removed for determination of cannabinoid CB(1) and CB(2) receptor protein density in the rats. SR144528 significantly attenuated the antinociceptive effect of Delta(9)THC in the arthritic rats [AD(50) = 3.3 (2.7-4) mg/kg], but not in the non-arthritic rats at a dose of 10/mg/kg. SR141716A significantly attenuated Delta(9)THC-induced antinociception in both the non-arthritic [AD(50) = 1.4 (0.8-2) mg/kg] and arthritic rat [AD(50) = 2.6 (1.8-3.1) mg/kg]. SR141716A or SR144528 alone did not result in a hyperalgesic effect as compared to vehicle. Our results indicate that the cannabinoid CB(2) receptor plays a critical role in cannabinoid-mediated antinociception, particularly in models of chronic inflammatory pain.

Authors+Show Affiliations

Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA 23298-0524, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

17588560

Citation

Cox, Melinda L., et al. "The Antinociceptive Effect of Delta9-tetrahydrocannabinol in the Arthritic Rat Involves the CB(2) Cannabinoid Receptor." European Journal of Pharmacology, vol. 570, no. 1-3, 2007, pp. 50-6.
Cox ML, Haller VL, Welch SP. The antinociceptive effect of Delta9-tetrahydrocannabinol in the arthritic rat involves the CB(2) cannabinoid receptor. Eur J Pharmacol. 2007;570(1-3):50-6.
Cox, M. L., Haller, V. L., & Welch, S. P. (2007). The antinociceptive effect of Delta9-tetrahydrocannabinol in the arthritic rat involves the CB(2) cannabinoid receptor. European Journal of Pharmacology, 570(1-3), pp. 50-6.
Cox ML, Haller VL, Welch SP. The Antinociceptive Effect of Delta9-tetrahydrocannabinol in the Arthritic Rat Involves the CB(2) Cannabinoid Receptor. Eur J Pharmacol. 2007 Sep 10;570(1-3):50-6. PubMed PMID: 17588560.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The antinociceptive effect of Delta9-tetrahydrocannabinol in the arthritic rat involves the CB(2) cannabinoid receptor. AU - Cox,Melinda L, AU - Haller,Victoria L, AU - Welch,Sandra P, Y1 - 2007/06/05/ PY - 2006/08/11/received PY - 2007/05/10/revised PY - 2007/05/15/accepted PY - 2007/6/26/pubmed PY - 2007/12/6/medline PY - 2007/6/26/entrez SP - 50 EP - 6 JF - European journal of pharmacology JO - Eur. J. Pharmacol. VL - 570 IS - 1-3 N2 - Cannabinoid CB(2) receptors have been implicated in antinociception in animal models of both acute and chronic pain. We evaluated the role both cannabinoid CB(1) and CB(2) receptors in mechanonociception in non-arthritic and arthritic rats. The antinociceptive effect of Delta(9)-tetrahydrocannabinol (Delta(9)THC) was determined in rats following administration of the cannabinoid CB(1) receptor-selective antagonist, SR141716A, the cannabinoid CB(2) receptor-selective antagonist, SR144528, or vehicle. Male Sprague-Dawley rats were rendered arthritic using Freund's complete adjuvant and tested for mechanical hyperalgesia in the paw-pressure test. Arthritic rats had a baseline paw-pressure of 83 +/- 3.6 g versus a paw-pressure of 177 +/- 6.42 g in non-arthritic rats. SR144528 or SR141716A (various doses mg/kg; i.p.) or 1:1:18 (ethanol:emulphor:saline) vehicle were injected 1 h prior to Delta(9)THC (4 mg/kg; i.p) or 1:1:18 vehicle and antinociception determined 30min post Delta(9)THC. AD(50)'s for both antagonists were calculated with 95% confidence limits. In addition, midbrain and spinal cord were removed for determination of cannabinoid CB(1) and CB(2) receptor protein density in the rats. SR144528 significantly attenuated the antinociceptive effect of Delta(9)THC in the arthritic rats [AD(50) = 3.3 (2.7-4) mg/kg], but not in the non-arthritic rats at a dose of 10/mg/kg. SR141716A significantly attenuated Delta(9)THC-induced antinociception in both the non-arthritic [AD(50) = 1.4 (0.8-2) mg/kg] and arthritic rat [AD(50) = 2.6 (1.8-3.1) mg/kg]. SR141716A or SR144528 alone did not result in a hyperalgesic effect as compared to vehicle. Our results indicate that the cannabinoid CB(2) receptor plays a critical role in cannabinoid-mediated antinociception, particularly in models of chronic inflammatory pain. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/17588560/abstract/The_antinociceptive_effect_of_Delta9_tetrahydrocannabinol_in_the_arthritic_rat_involves_the_CB_2__cannabinoid_receptor L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(07)00625-5 DB - PRIME DP - Unbound Medicine ER -