CHARACTERISTICS OF TOLERANCE TO SOMATIC AND VISCERAL ANTINOCICEPTION AFTER CONTINUOUS EPIDURAL INFUSION OF MORPHINE IN RATS

A continuous epidural infusion of morphine may cause a complicated tol erance to develop, depending on the spinal and supraspinal sites. We d esigned this study to clarify the characteristics of the tolerance to somatic and visceral antinociception after epidural morphine infusion. Rats received epidural infusion of morphine at the rates of 50 or 100 mu g . kg(-1). h(-1), or isotonic sodium chloride solution for 7 days . The tail-flick (TF) test and colorectal distension (CD) test were us ed to measure the somatic and visceral antinociceptive effects, respec tively. Nociceptive tests were performed on Days 1, 2, 3, 4, and 7. Af ter 7 days, time-response curves after epidural morphine (10 mu g) or intraperitoneal morphine (3 mg) challenge tests were conducted to asse ss the magnitude of tolerance. Epidurally infused morphine significant ly increased percent maximal possible effects (%MPEs) (P < 0.05) in bo th the TF and CD tests, depending on the concentration of morphine. In the epidural morphine challenge test, increases in %MPEs were signifi cantly attenuated (P < 0.05) in the morphine-infused group compared wi th the isotonic sodium chloride solution-infused group. The increases in %MPEs in the intraperitoneal challenge test were also attenuated in the morphine-infused group. We conclude that morphine tolerance to bo th somatic and visceral antinociception develops rapidly during epidur al infusion and is based on the development of tolerance at the system ic, as well as the epidural, level. Implications: A continuous epidura l infusion of morphine rapidly induces tolerance to visceral and somat ic antinociception in rats. This development is based on the developme nt of tolerance at the systemic, as well as the epidural, level.