ABSTRACT

It has been long suspected that the cannabinoid system participates in the antinociceptive effects of nonsteroidal anti-inflammatory drugs. We studied the possible effects of cannabinoid receptor antagonism on diclofenac-induced antinociception in the writhing test in mice.

In our study, male BALB/c mice, weighing 20-30 g, were used. Writhing responses were produced by intraperitoneal injection of 0.6% acetic acid. Different doses of diclofenac (3, 10, 30 mg/kg, i.p.) were tested, then the influence of AM-251 (1 mg/kg, i.p.), a cannabinoid CB1 receptor antagonist and AM-630 (3 mg/kg, i.p.), a cannabinoid CB2 receptor antagonist on the antinociceptive effects of diclofenac was studied.

Diclofenac administration elicited a significant, dose-dependent antinociceptive response; however, neither the cannabinoid CB1 receptor antagonist AM-251 nor the cannabinoid CB2 receptor antagonist AM-630 had any influence on the antinociceptive effect of diclofenac.

Iinhibition of cannabinoid receptors does not contribute to the antinociceptive action of systemic diclofenac. Further studies are needed to explain the antinociceptive mechanism of diclofenac.

Keywords: AM-251, AM-630, antinociception, cannabinoid receptors, diclofenac