Evidence for a central but not a peripheral analgesic effect of clomipramine in rats.
The effect of clomipramine (CMI), a tricyclic antidepressant, was studied on an acute inflammatory pain model in an attempt to understand its potential antinociceptive activity, the involvement of a central and/or peripheral component and its influence on the inflammatory process. When administered (i.v.) before the inflammatory agent, carrageenan (CAR), CMI (0.125, 0.25 and 0.5 mg/kg) completely prevented the development of the hyperalgesia for 70-120 min according to the doses. This antinociceptive effect was suppressed by naloxone (100 micrograms/kg i.v.) for 65 min. Neither higher doses (1, 2 and 20 mg/kg, i.v.) nor CMI injected into the inflamed paw (15 min before CAR) modified pain thresholds. Moreover, CMI (0.5 and 2 mg/kg, i.v.) administered 15 min before CAR markedly increased the volume of the CAR-induced oedema. These results (1) demonstrate an opioid-dependent antinociceptive effect of CMI on this model, the doses used being lower than those active in thermal or electrical tests, and (2) tend to exclude a peripheral mechanism and an NSAID-like anti-inflammatory activity suggested by previous in vitro studies.
Ardid
D
D
Laboratoire de Pharmacologie Médicale, INSERM U195, Faculté de Médecine, 63001 Clermonl-Ferrand Cedex France.
Eschalier
A
A
Lavarenne
J
J
D000700:Analgesics; D000818:Animals; D002490:Central Nervous System / Q000187:drug effects*; D002997:Clomipramine / Q000494:pharmacology*; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D005528:Foot; D007267:Injections; D007275:Injections, Intravenous; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D010146:Pain / Q000503:physiopathology; D010525:Peripheral Nerves / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D012684:Sensory Thresholds / Q000187:drug effects
D000700:Analgesics; D009270:Naloxone; D002997:Clomipramine