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, T. Nyári, G. Benedek, G. Horváth

Research output: Contribution to journalArticle

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 - 2010

Fingerprint

Ankle Joint
Arthritis
Joints
Ligands
Cannabinoid Receptor Antagonists
Topical Administration
Cannabinoid Receptors
Cannabinoids
Carrageenan
Hyperalgesia
Opioid Receptors
Pharmaceutical Preparations
Opioid Analgesics
2-arachidonylglycerol
endomorphin 1
Edema
Leg
Hypersensitivity
Inflammation
Injections

Keywords

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

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Pharmacology

Cite this

Peripheral antinociceptive effect of 2-arachidonoyl-glycerol and its interaction with endomorphin-1 in arthritic rat ankle joints. / Mecs, Laszlo; Tuboly, Gabor; Toth, Kalman; Nagy, Endre; Nyári, T.; Benedek, G.; Horváth, G.

In: Clinical and Experimental Pharmacology and Physiology, Vol. 37, No. 5-6, 2010, p. 544-550.

Research output: Contribution to journalArticle

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AU - Benedek, G.

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