Adrenergic mechanisms in antinociceptive effects of non steroidal anti-inflammatory drugs in acute thermal nociception in mice

Objective: The interactions of alpha-adrenoceptors with the antinociceptive effects of non-steroidal anti-inflammatory drugs (NSAIDs) were assessed in acute thermal nociception in mice. Materials and methods: The analgesic effect was analyzed by the tail-flick test. Results: The pretreatment with yohimbine (1 mg/kg i.p.), 30 min prior to the intraperitoneal injection of ketoprofen (50 mg/kg), diclofenac (30 mg/kg) and piroxicam (50 mg/kg) antagonized the antinociception induced by these NSAIDs, significantly reducing the tail-flick latency. Yohimbine did not affect paracetamol (125 mg/kg) induced antinociception. Prazosin (I mg/kg i.p.) antagonized only the effect of paracetamol, without affecting the latency of the other drugs. When NSAIDs were administered i.t. (ketoprofen 2 m/kg; diclofenac 0.9 mg/kg; piroxicam 1.5 mg/kg; paracetamol 3.75 mg/kg), the same results were obtained after i.p. pretreatment with yohimbine and prazosin. The pretreatment of phenoxybenzamine (1 mg/kg i.p.) antagonized all antinociceptive effects. Conclusions: NSAIDs induced antinociception in an acute thermal pain model without inflammation. The mechanism of antinociception induced by ketoprofen, diclofenac and piroxicam involves an activation of alpha(2)-adrenoceptors at spinal and supraspinal levels, while paracetamol-induced antinociception is probably due mainly to central activation of the descending noradrenergic inhibitory system by alpha(1)-adrenoceptors.