Effects of the analgesic agent tramadol in normal and arthritic rats: comparison with the effects of different opioids, including tolerance and cross-tolerance to morphine.
The effects of the analgesic agent tramadol (0.1-1 mg/kg i.v.) were compared to those of the mixed agonist-antagonist analgesics nalbuphine (1 mg/kg i.v.) and buprenorphine (3 micrograms/kg i.v.) in the vocalization threshold to paw pressure test. Normal and Freund's adjuvant-induced arthritic rats were used. We have shown previously that these animals used as a model of clinical pain exhibit an enhanced sensitivity to morphine (0.1-1 mg/kg i.v.), with a rapid development of tolerance after repetitive low doses, a response not observed in normal rats. In the present study, the antinociceptive effects of tramadol, buprenorphine and nalbuphine were enhanced (by 2- to 5-fold) in arthritic compared to normal rats. In this model, these effects were significantly reduced by a dose of naloxone (0.1 mg/kg i.v.) that completely antagonized the effect of morphine. In this model, the antinociceptive effect of tramadol (1 mg/kg i.v.) was comparable to that of nalbuphine (1 mg/kg i.v.), buprenorphine (3 micrograms/kg i.v.) and morphine (1 mg/kg i.v.). Repeated administration of low doses of tramadol twice daily for 4 days to arthritic rats did not induce tolerance, in contrast to nalbuphine, buprenorphine, and morphine. In addition, no cross-tolerance between tramadol and morphine was observed in these animals.
Kayser
V
V
Unité de Recherche de Physiopharmacologie du Système Nerveux, I.N.S.E.R.M., U 161, Paris, France.
Besson
J M
JM
Guilbaud
G
G
D000818:Animals; D001168:Arthritis / Q000503:physiopathology*; D002047:Buprenorphine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009266:Nalbuphine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D010147:Pain Measurement; D051381:Rats; D011919:Rats, Inbred Strains; D014147:Tramadol / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D009270:Naloxone; D014147:Tramadol; D002047:Buprenorphine; D009020:Morphine; D009266:Nalbuphine