Comparative antinociceptive effect of arachidonylcyclopropylamide, a cannabinoid 1 receptor agonist & lignocaine, a local anaesthetic agent, following direct intrawound administration in rats

BACKGROUND & OBJECTIVES: Treatment of inflammatory pain with opioids is accompanied by unpleasant and, at times, life-threatening side effects. Cannabis produces antinociception as well as psychotropic effects. It was hypothesized that peripheral cannabinoid receptors outside the central nervous system could be selectively activated for relief of pain. This study was undertaken to measure the antinociceptive effect of type 1 cannabinoid receptor (CB1r) agonist arachidonylcyclopropylamide (ACPA) in a rat model of inflammatory pain after intrawound administration and the effects were compared with lignocaine. METHODS: Wounds were produced under controlled conditions by an incision in the right hind paw in rats. ACPA (10, 30 or 100 μg/10 μl) was administered directly into the wound. Antinociception was evaluated by guarding, allodynia and thermal hyperalgesia. This was compared to lignocaine (30 μg/10 μl). Reversal of ACPA (30 μg)-mediated antinociceptive effect was attempted by intrawound AM251 (100 μg), a CB1r antagonist. Antinociception was also evaluated after contralateral administration of ACPA (30 μg). Primary afferent nociceptive input to the spinal cord was investigated by c-Fos expression after ACPA treatment (100 μg). RESULTS: ACPA, but not lignocaine, inhibited guarding behaviour, which was locally mediated. Conversely, lignocaine, but not ACPA, inhibited thermal hyperalgesia and mechanical allodynia. ACPA-mediated inhibitory effect was reversible and dose dependent. It was associated with a decreased c-Fos expression. Locomotor activity was unaffected following ACPA (100 μg) treatment. INTERPRETATION & CONCLUSIONS: Lignocaine attenuated evoked pain behaviour whereas ACPA decreased guarding score. This difference was likely due to blockade of sodium ion channels and the activation of peripheral CB1r, respectively. Central side effects were absent after ACPA treatment. Further studies need to be done to assess the effect of ACPA treatment in clinical conditions.