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Opioid receptor and NO/cGMP pathway as a mechanism of peripheral antinociceptive action of the cannabinoid receptor agonist anandamide.
Life Sci. 2009 Aug 26; 85(9-10):351-6.LS

Abstract

AIMS

In this study, we investigated whether the opioid system and the nitric oxide pathway were involved in the peripheral antinociception induced by a cannabinoid receptor agonist anandamide.

MAIN METHODS

Hyperalgesia was induced by a subcutaneous injection of carrageenan (250 microg) into the plantar surface of the rat's hindpaw and measured by the paw pressure test 3h after injection. The weight in grams (g) required to elicit a nociceptive response, paw flexion, was determined as the nociceptive threshold.

KEY FINDINGS

Anandamide elicited a dose-dependent (50, 75, and 100 ng per paw) antinociceptive effect. The highest dose of anandamide did not produce antihyperalgesia in the contralateral paw, indicating a peripheral site of action. The CB(1) receptor antagonist AM251 (20, 40, 80 and 160mug per paw) antagonized peripheral antihyperalgesia induced by anandamide (100 ng), in a dose-dependent manner, suggesting CB(1) receptor activation. Anandamide-induced peripheral antihyperalgesia was reverted by blockers of the l-arginine/NO/cGMP pathway N(G)-nitro-l-arginine (NOARG; 24, 36 and 48 microg per paw) and 1H-[1,2,4] Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 25, 50 and 100 microg per paw), in a dose-dependent manner. Furthermore, opioid receptor antagonist naloxone (12.5, 25 and 50 microg per paw) antagonized the peripheral antihyperalgesia induced by anandamide.

SIGNIFICANCE

This study provides evidence that the peripheral antinociceptive effect of the cannabinoid receptor agonist anandamide may result from l-arginine/NO/cGMP pathway activation and that the opioid system is also involved.

Authors+Show Affiliations

Department of Pharmacology, Institute of Biological Sciences, UFMG, 31270-100, Belo Horizonte, MG, CEP: 31.270-100, Brazil.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

19576231

Citation

Reis, Gláucia Maria Lopes, et al. "Opioid Receptor and NO/cGMP Pathway as a Mechanism of Peripheral Antinociceptive Action of the Cannabinoid Receptor Agonist Anandamide." Life Sciences, vol. 85, no. 9-10, 2009, pp. 351-6.
Reis GM, Pacheco D, Perez AC, et al. Opioid receptor and NO/cGMP pathway as a mechanism of peripheral antinociceptive action of the cannabinoid receptor agonist anandamide. Life Sci. 2009;85(9-10):351-6.
Reis, G. M., Pacheco, D., Perez, A. C., Klein, A., Ramos, M. A., & Duarte, I. D. (2009). Opioid receptor and NO/cGMP pathway as a mechanism of peripheral antinociceptive action of the cannabinoid receptor agonist anandamide. Life Sciences, 85(9-10), 351-6. https://doi.org/10.1016/j.lfs.2009.06.012
Reis GM, et al. Opioid Receptor and NO/cGMP Pathway as a Mechanism of Peripheral Antinociceptive Action of the Cannabinoid Receptor Agonist Anandamide. Life Sci. 2009 Aug 26;85(9-10):351-6. PubMed PMID: 19576231.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Opioid receptor and NO/cGMP pathway as a mechanism of peripheral antinociceptive action of the cannabinoid receptor agonist anandamide. AU - Reis,Gláucia Maria Lopes, AU - Pacheco,Daniela, AU - Perez,Andréa Castro, AU - Klein,André, AU - Ramos,Marina Abadia, AU - Duarte,Igor Dimitri Gama, Y1 - 2009/07/01/ PY - 2009/02/13/received PY - 2009/06/22/revised PY - 2009/06/24/accepted PY - 2009/7/7/entrez PY - 2009/7/7/pubmed PY - 2009/9/16/medline SP - 351 EP - 6 JF - Life sciences JO - Life Sci VL - 85 IS - 9-10 N2 - AIMS: In this study, we investigated whether the opioid system and the nitric oxide pathway were involved in the peripheral antinociception induced by a cannabinoid receptor agonist anandamide. MAIN METHODS: Hyperalgesia was induced by a subcutaneous injection of carrageenan (250 microg) into the plantar surface of the rat's hindpaw and measured by the paw pressure test 3h after injection. The weight in grams (g) required to elicit a nociceptive response, paw flexion, was determined as the nociceptive threshold. KEY FINDINGS: Anandamide elicited a dose-dependent (50, 75, and 100 ng per paw) antinociceptive effect. The highest dose of anandamide did not produce antihyperalgesia in the contralateral paw, indicating a peripheral site of action. The CB(1) receptor antagonist AM251 (20, 40, 80 and 160mug per paw) antagonized peripheral antihyperalgesia induced by anandamide (100 ng), in a dose-dependent manner, suggesting CB(1) receptor activation. Anandamide-induced peripheral antihyperalgesia was reverted by blockers of the l-arginine/NO/cGMP pathway N(G)-nitro-l-arginine (NOARG; 24, 36 and 48 microg per paw) and 1H-[1,2,4] Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 25, 50 and 100 microg per paw), in a dose-dependent manner. Furthermore, opioid receptor antagonist naloxone (12.5, 25 and 50 microg per paw) antagonized the peripheral antihyperalgesia induced by anandamide. SIGNIFICANCE: This study provides evidence that the peripheral antinociceptive effect of the cannabinoid receptor agonist anandamide may result from l-arginine/NO/cGMP pathway activation and that the opioid system is also involved. SN - 1879-0631 UR - https://www.unboundmedicine.com/medline/citation/19576231/Opioid_receptor_and_NO/cGMP_pathway_as_a_mechanism_of_peripheral_antinociceptive_action_of_the_cannabinoid_receptor_agonist_anandamide_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0024-3205(09)00283-5 DB - PRIME DP - Unbound Medicine ER -