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The mu-opioid receptor agonist morphine, but not agonists at delta- or kappa-opioid receptors, induces peripheral antinociception mediated by cannabinoid receptors.
Br J Pharmacol. 2008 Jul; 154(5):1143-9.BJ

Abstract

BACKGROUND AND PURPOSE

Although participation of opioids in antinociception induced by cannabinoids has been documented, there is little information regarding the participation of cannabinoids in the antinociceptive mechanisms of opioids. The aim of the present study was to determine whether endocannabinoids could be involved in peripheral antinociception induced by activation of mu-, delta- and kappa-opioid receptors.

EXPERIMENTAL APPROACH

Nociceptive thresholds to mechanical stimulation of rat paws treated with intraplantar prostaglandin E2 (PGE2, 2 microg) to induce hyperalgesia were measured 3 h after injection using an algesimetric apparatus. Opioid agonists morphine (200 microg), (+)-4-[(alphaR)-alpha-((2S,5R)-4-Allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide (SNC80) (80 microg), bremazocine (50 microg); cannabinoid receptor antagonists N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251) (20-80 microg), 6-iodo-2-methyl-1-[2-(4-morpholinyl)ethyl]-1H-indol-3-yl(4-methoxyphenyl) methanone (AM630) (12.5-100 microg); and an inhibitor of methyl arachidonyl fluorophosphonate (MAFP) (1-4 microg) were also injected in the paw.

KEY RESULTS

The CB1-selective cannabinoid receptor antagonist AM251 completely reversed the peripheral antinociception induced by morphine in a dose-dependent manner. In contrast, the CB2-selective cannabinoid receptor antagonist AM630 elicited partial antagonism of this effect. In addition, the administration of the fatty acid amide hydrolase inhibitor, MAFP, enhanced the antinociception induced by morphine. The cannabinoid receptor antagonists AM251 and AM630 did not modify the antinociceptive effect of SNC80 or bremazocine. The antagonists alone did not cause any hyperalgesic or antinociceptive effect.

CONCLUSIONS AND IMPLICATIONS

Our results provide evidence for the involvement of endocannabinoids, in the peripheral antinociception induced by the mu-opioid receptor agonist morphine. The release of cannabinoids appears not to be involved in the peripheral antinociceptive effect induced by kappa- and delta-opioid receptor agonists.

Authors+Show Affiliations

Department of Pharmacology, Institute of Biological Sciences, UFMG, Av. Antônio Carlos, Belo Horizonte, Brazil.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

18469844

Citation

da Fonseca Pacheco, D, et al. "The Mu-opioid Receptor Agonist Morphine, but Not Agonists at Delta- or Kappa-opioid Receptors, Induces Peripheral Antinociception Mediated By Cannabinoid Receptors." British Journal of Pharmacology, vol. 154, no. 5, 2008, pp. 1143-9.
da Fonseca Pacheco D, Klein A, de Castro Perez A, et al. The mu-opioid receptor agonist morphine, but not agonists at delta- or kappa-opioid receptors, induces peripheral antinociception mediated by cannabinoid receptors. Br J Pharmacol. 2008;154(5):1143-9.
da Fonseca Pacheco, D., Klein, A., de Castro Perez, A., da Fonseca Pacheco, C. M., de Francischi, J. N., & Duarte, I. D. (2008). The mu-opioid receptor agonist morphine, but not agonists at delta- or kappa-opioid receptors, induces peripheral antinociception mediated by cannabinoid receptors. British Journal of Pharmacology, 154(5), 1143-9. https://doi.org/10.1038/bjp.2008.175
da Fonseca Pacheco D, et al. The Mu-opioid Receptor Agonist Morphine, but Not Agonists at Delta- or Kappa-opioid Receptors, Induces Peripheral Antinociception Mediated By Cannabinoid Receptors. Br J Pharmacol. 2008;154(5):1143-9. PubMed PMID: 18469844.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The mu-opioid receptor agonist morphine, but not agonists at delta- or kappa-opioid receptors, induces peripheral antinociception mediated by cannabinoid receptors. AU - da Fonseca Pacheco,D, AU - Klein,A, AU - de Castro Perez,A, AU - da Fonseca Pacheco,C M, AU - de Francischi,J N, AU - Duarte,I D G, Y1 - 2008/05/12/ PY - 2008/5/13/pubmed PY - 2008/10/3/medline PY - 2008/5/13/entrez SP - 1143 EP - 9 JF - British journal of pharmacology JO - Br J Pharmacol VL - 154 IS - 5 N2 - BACKGROUND AND PURPOSE: Although participation of opioids in antinociception induced by cannabinoids has been documented, there is little information regarding the participation of cannabinoids in the antinociceptive mechanisms of opioids. The aim of the present study was to determine whether endocannabinoids could be involved in peripheral antinociception induced by activation of mu-, delta- and kappa-opioid receptors. EXPERIMENTAL APPROACH: Nociceptive thresholds to mechanical stimulation of rat paws treated with intraplantar prostaglandin E2 (PGE2, 2 microg) to induce hyperalgesia were measured 3 h after injection using an algesimetric apparatus. Opioid agonists morphine (200 microg), (+)-4-[(alphaR)-alpha-((2S,5R)-4-Allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide (SNC80) (80 microg), bremazocine (50 microg); cannabinoid receptor antagonists N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251) (20-80 microg), 6-iodo-2-methyl-1-[2-(4-morpholinyl)ethyl]-1H-indol-3-yl(4-methoxyphenyl) methanone (AM630) (12.5-100 microg); and an inhibitor of methyl arachidonyl fluorophosphonate (MAFP) (1-4 microg) were also injected in the paw. KEY RESULTS: The CB1-selective cannabinoid receptor antagonist AM251 completely reversed the peripheral antinociception induced by morphine in a dose-dependent manner. In contrast, the CB2-selective cannabinoid receptor antagonist AM630 elicited partial antagonism of this effect. In addition, the administration of the fatty acid amide hydrolase inhibitor, MAFP, enhanced the antinociception induced by morphine. The cannabinoid receptor antagonists AM251 and AM630 did not modify the antinociceptive effect of SNC80 or bremazocine. The antagonists alone did not cause any hyperalgesic or antinociceptive effect. CONCLUSIONS AND IMPLICATIONS: Our results provide evidence for the involvement of endocannabinoids, in the peripheral antinociception induced by the mu-opioid receptor agonist morphine. The release of cannabinoids appears not to be involved in the peripheral antinociceptive effect induced by kappa- and delta-opioid receptor agonists. SN - 0007-1188 UR - https://www.unboundmedicine.com/medline/citation/18469844/The_mu_opioid_receptor_agonist_morphine_but_not_agonists_at_delta__or_kappa_opioid_receptors_induces_peripheral_antinociception_mediated_by_cannabinoid_receptors_ DB - PRIME DP - Unbound Medicine ER -