Epidural ketamine potentiates epidural morphine but not fentanyl in acute nociception in rats

European Journal of Pain - Tập 7 - Trang 121-130 - 2003
Vincent L.H Hoffmann1,2, Alexis K Baker2, Marcel P Vercauteren1, Hugo F Adriaensen1, Theo F Meert2
1University Hospital Antwerp, Edegem, Belgium
2CNS Pain Discovery Group, Johnson and Johnson PRD, CNS Pain, Turnhoutsewg 30, B-2340, Beerse, Belgium

Tóm tắt

AbstractEpidural opioids have been reported to provide superior analgesia in acute pain management. Despite the fact that the required doses are low, major side effects such as respiratory depression may still occur. In an effort to maximize analgesia and to minimize the rate of side effects, epidural NMDA receptor antagonists, especially ketamine, may be co‐administered with opioids. This study investigated whether ketamine had beneficial effects on fentanyl‐ or morphine‐induced antinociception in an acute pain model in rats.In male Wistar rats, an epidural catheter was placed under general anaesthesia. After 1 week the animals were subjected to the tail withdrawal reaction (TWR) test. After determination of the basal reaction latencies, fentanyl, morphine, ketamine or combinations of an opioid with ketamine were administered epidurally. TWR latencies were measured for up to 2 h after treatment.Both opioids showed a dose related antinociceptive effect. Fentanyl had a fast onset and a short duration of action whereas the reverse was true for morphine. Ketamine exhibited only limited antinociceptive properties. In the combinations, ketamine improved morphine‐induced antinociception both in terms of maximal possible effect (MPE) as well as in duration of action. The combination of fentanyl with ketamine did not result in any improvement, neither in terms of MPE nor in duration of action. Moreover, increasing doses of ketamine tended to decrease the MPE of various doses of fentanyl. These data confirm that ketamine, contrary to opioids, does not possess important antinociceptive properties in an acute test such as the TWR test. Furthermore, these data indicate that additive drugs such as ketamine may have different effects on different opioids.

Tài liệu tham khảo

Aanonsen L.M., 1987, Nociceptive action of excitatory amino acids in the mouse: effects of spinally administered opioids, phencyclidine and sigma agonists, J. Pharmacol. Exp. Ther., 243, 9 10.1016/S0304-3959(96)03185-5 10.1016/0006-8993(92)90780-D 10.1097/00000539-199806000-00021 10.1097/00000542-198409000-00008 10.1016/S0091-3057(96)00462-5 Finney D.J., 1971, Statistical Methods in Biological Assay 10.1016/0006-8993(90)91247-E 10.1515/DMDI.1991.9.2.77 Gebhardt B, 1994, Pharmacology and clinical results with peridural and intrathecal administration of ketamine, Anaesthesist, 43, S34 10.1097/00000542-198111000-00007 GomesI GuptaA BansinathM DeviLA.Ketamine potentiates Morphine Activation of the MAPK Pathway. Presented at International Narcotics Research 31st Conference2000 Seattle (WA) USA. 10.1016/0304-3959(85)90001-6 10.1046/j.1365-201X.1996.566309000.x 10.1097/00000542-198803000-00025 Henthorn T.K., 1999, Active transport of fentanyl by the blood—brain barrier, J. Pharmacol. Exp. Ther., 289, 1084 10.1097/00000542-199901000-00023 10.1097/00001756-199602290-00037 10.1111/j.1600-0773.1995.tb01041.x 10.1111/j.1399-6576.1982.tb01765.x 10.1016/S0893-133X(00)00143-3 10.1213/00000539-198708000-00007 10.1213/00000539-199311000-00030 10.2165/00003495-199958050-00002 10.1097/00000539-199807000-00022 Leysen J.E., 1978, Characteristics and Function of Opioids, 479 10.1213/00000539-198903000-00031 10.1097/00000542-199301000-00016 10.1016/0304-3959(95)00073-2 10.1038/383819a0 10.1097/00000542-199201000-00014 10.1073/pnas.96.14.7731 10.1523/JNEUROSCI.15-03-02396.1995 10.1073/pnas.241296098 10.1016/S0024-3205(01)01008-6 10.1177/107385840100700307 10.1111/j.1365-2044.1989.tb11440.x 10.1016/0304-3959(82)90170-1 10.1097/00000542-199212000-00021 10.1097/00000542-198706000-00019 10.1097/00000542-199109000-00012 10.1007/978-1-4684-0123-3 10.1016/0028-3908(87)90084-0 10.1126/science.1824728 10.1016/S0091-3057(97)00011-7 10.1111/j.1399-6576.1992.tb03458.x Wong C.S., 1996, Ketamine potentiates analgesic effect of morphine in postoperative epidural pain control, Reg. Anesth., 21, 534 10.1097/00000542-199712000-00003 10.1016/0304-3959(91)90100-C
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European Journal of Pain

Tập 7

121-130

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