Peripheral antinociceptive effect of 2-arachidonoyl-glycerol and its interaction with endomorphin-1 in arthritic rat ankle joints.

Abstract

1. Both cannabinoid and opioid receptors are localized at the peripheral level, and drugs acting on these receptors may produce antinociception after topical administration; however, the effect of endogenous ligands at these receptors is poorly understood. Our goal was to determine the antinociceptive potency of the endogenous cannabinoid 2-arachidonoyl-glycerol (2-AG), and its interaction with endomorphin-1 (EM1) at joint level in the rat inflammation model. 2. Mechanical hypersensitivity was produced by injection of carrageenan (300 microg/30 microL) into the tibiotarsal joint of the right hind leg. The mechanical threshold was assessed by von Frey filaments. 2-AG (3-200 microg), EM1 (100-300 microg) and their combinations in a fixed-dose ratio (1 : 10) were given into the inflamed joint, and the threshold was determined repeatedly for 105 min after the drug administrations. 3. Both ligands produced dose-dependent anti-hyperalgesia, and the highest doses caused prolonged effects, but they did not influence the degree of oedema and the withdrawal threshold at the non-inflamed side. EM1 had lower potency compared to 2-AG (ED(25): 233 (CI: 198-268) microg and 126 (CI: 88-162) microg, respectively; P < 0.05). The effects of EM1 and 2-AG were prevented by mu-opioid and cannabinoid 1 receptor antagonists, respectively. The ED(25) value for the combination (98 (CI: 80-112) microg) did not differ significantly from the value of 2-AG; however, the largest dose combination produced a significantly higher effect than the ligands by themselves. 4. Our data showed that 2-AG was an effective antinociceptive ligand at joint level, and its combination with EM1 produced long-lasting, effective antinociception.

• Authors: Laszlo Mecs, Gabor Tuboly, Kalman Toth, Endre Nagy, Tibor Nyari, Gyorgy Benedek, Gyöngyi Horvath
• Journal: Clinical and experimental pharmacology & physiology (Clin Exp Pharmacol Physiol) Vol. 37 Issue 5-6 Pg. 544-50 (May 2010) ISSN: 1440-1681 [Electronic] Australia
• PMID: 20529093 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Analgesics, Opioid
• Arachidonic Acids
• Cannabinoid Receptor Modulators
• Endocannabinoids
• Glycerides
• Ligands
• Narcotic Antagonists
• Oligopeptides
• Receptors, Cannabinoid
• Receptors, Opioid
• endomorphin 1
• glyceryl 2-arachidonate

Topics

• Analgesics, Opioid (administration & dosage, pharmacology, therapeutic use)
• Animals
• Arachidonic Acids (administration & dosage, pharmacology, therapeutic use)
• Arthritis, Experimental (drug therapy, metabolism)
• Cannabinoid Receptor Modulators (administration & dosage, pharmacology, therapeutic use)
• Dose-Response Relationship, Drug
• Drug Synergism
• Edema (drug therapy, metabolism)
• Endocannabinoids
• Glycerides (administration & dosage, pharmacology, therapeutic use)
• Ligands
• Male
• Narcotic Antagonists (pharmacology)
• Oligopeptides (administration & dosage, pharmacology, therapeutic use)
• Pain Threshold (drug effects)
• Rats
• Rats, Wistar
• Receptors, Cannabinoid (metabolism)
• Receptors, Opioid (metabolism)
• Tarsal Joints (drug effects, metabolism)