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 antiinflammatory drugs (NSAIDs) were assessed in acute thermal nociception in mice.


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 (1 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 alpha2-adrenoceptors at spinal and supraspinal levels, while paracetamol-induced antinociception is probably due mainly to central activation of the descending noradrenergic inhibitory system by alpha1-adrenoceptors.
Pinardi
G
G
Pharmacology Program, ICBM, Faculty of Medicine, University of Chile, Santiago. gpinardi@machi.med.uchile.cl
Sierralta
F
F
Miranda
H F
HF
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D006358:Hot Temperature / Q000009:adverse effects*; D051379:Mice; D009619:Nociceptors / Q000187:drug effects*; D010147:Pain Measurement / Q000187:drug effects; D010643:Phenoxybenzamine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011930:Reaction Time / Q000187:drug effects; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000502:physiology*; D015016:Yohimbine / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D011942:Receptors, Adrenergic, alpha; D010643:Phenoxybenzamine; D015016:Yohimbine; D011224:Prazosin