Changes in cerebral cAMP and PKA levels, during development of acute opioid tolerance induced by remifentanil in mice / 中华麻醉学杂志

ABSTRACT

Objective To investigate the changes in cerebral cAMP and PKA levels during development of acute opioid tolerance induced by remifentanil and to determine whether post-receptor cAMP/PKA signaling pathway is involved in the process. Methods Fifty-six male Kunming mice weighing 25-35 g were randomly divided into 5 groups group Ⅰ control (C) (n=8); group Ⅱ received morphine infused intraperitoneally (IP) at 0.6 μg'kg-1·min-1 for 120min(M) (n=8); group Ⅲ,Ⅳ,Ⅴ received remifentnil infused IP at 0.4, 0.8 and 1.6 μg·kg-1·min-1 for 120 min(R1=8, R2n=8; R3 n=24).Control group received IP infusion of normal saline. Tail-flick test was performed td measure the response of animals to a thermal nociceptive stimulus before IP infusion, at 30, 60, 90 and 120 min after beginning of IP infusion and at 15, 30, 45 and 60 min after termination of IP infusion. Eight animals were decapitated at 60 min after termination of IP infusion in all 5 groups and the other 16 animals in group R3 were decapitated at 30 and 45 min after termination of IP infusion (n=8 each) for determination of intracellular contents of cAMP and activities of PKA in cerebral cortex and inferior colliculus-striatum by ELISA or radioactive isotope [32p,] ATP-catalyzing assay. Results The tail-flick latency was significantly prolonged during IP infusion as compared with the baseline before infusion in group M, R1 , R2 and R3 but became significantly shorter at 30 and 45 min after infusion than the baseline values in group R1, R2 and R3indicating hyperalgesia after remifentauil infusion. The cerebral contents of cAMP and PKA activities at 60 min after termination of infusion were comparable or decreased in group M, R1, R2 and R3 as compared with group C. There was no significant difference in cerebral cAMP contents and PKA activities at 30, 60 and 45 min after IP remifentanil infusion in group R3. Conclusion Remifentanil can induce acute hyperalgesic effect on mice, and there is no up-regulation of post-receptor cAMP/PKA signaling pathway in the acute opioid tolerance, which is not similar to that chronic opioid tolerance.