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

Laszlo Mecs, Gabor Tuboly, Kalman Toth, Endre Nagy, Tibor Nyari, Gyorgy Benedek, Gyöngyi Horvath

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13 Citations (Scopus)

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 μg/30 μL) into the tibiotarsal joint of the right hind leg. The mechanical threshold was assessed by von Frey filaments. 2-AG (3-200 μg), EM1 (100-300 μg) 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 (ED25: 233 (CI: 198-268) μg and 126 (CI: 88-162) μg, respectively; P < 0.05). The effects of EM1 and 2-AG were prevented by μ-opioid and cannabinoid 1 receptor antagonists, respectively. The ED25 value for the combination (98 (CI: 80-112) μg) 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.

Original languageEnglish
Pages (from-to)544-550
Number of pages7
JournalClinical and Experimental Pharmacology and Physiology
Volume37
Issue number5-6
DOIs
Publication statusPublished - Jan 1 2010

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Keywords

  • Antinociceptive activity
  • Arthritis
  • Cannabinoid
  • Inflammation
  • Interaction
  • Opioid
  • Pain
  • Peripheral sensory neurons

ASJC Scopus subject areas

  • Physiology
  • Pharmacology
  • Physiology (medical)

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