Antinociceptive activity of a novel CB1 receptor agonist in pain and its anti-exudative effect in inflammation in experiment

Objective. To study in experiment antinociceptive activity of cannabinoid CB1 receptor agonist (derivative of 2H-chromene, code CHR) in models of visceral postoperative and neuropathic pain, and to assess the contribution of its potential anti-exudative effect to mechanism of antinociceptive action. Material and methods. The study was conducted on CD-1 mice and Sprague Dawley rats. Animals were administered the 2H-chromene derivative CHR orally at an effective dose of 5 mg/kg. Antinociceptive activity of CHR compound was evaluated in models of postoperative and neuropathic pain in comparison with effects of tramadol 20 mg/kg and gabapentin 100 mg/kg. Anti-exudative and antinociceptive effects of CHR compound were investigated after a single administration to rats in a model of hind paw edema induced by carrageenan. We compared these effects with those following injection of sodium diclofenac 10 mg/kg. Results. CHR compound increased pain threshold by 40 times in postoperative pain model, in experimental neuropathic pain — by 3.5, 70 and 100 times within 1-7 days, respectively. Antinociceptive effect of CHR was not inferior tramadol and gabapentin. In hind paw edema model, CHR compound reduced exudation by 42%, while sodium diclofenac decreased exudation by 67%. Both compounds increased pain threshold by 15 times (p<0.05). Conclusion. The 2H chromene derivative CHR at effective dose of 5 mg/kg demonstrates antinociceptive effect in experimental postoperative and neuropathic pain. CHR inhibits exudation less effectively than sodium diclofenac but demonstrates comparable antinociceptive activity.