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Introduction: Amongst the medications to reduce pain, morphine as an important natural and tramadol as an important synthetic drug have been mostly considered. There are few studies on the comparison of the analgesic effect of these drugs in neonatal and perpubertal periods. Methods: Neonate rats (n=49) were randomly divided into three groups. On postnatal days 8-14, one group received saline and the two other groups received tramadol and morphine with increasing doses. On postnatal day 21, each group was divided into subgroups, which received each of morphine, tramadol or saline on postnatal days 22-28 (either for the first time or re-exposure). On postnatal days of 22 and 28, the pain-related behavior was tested by hot plate test. Results: Exposure to morphine significantly increased latency of reaction in hot plate test chronic morphine administration (p28) had a greater effect compared to single dose morphine administration (p22). Tramadol had no significant effect. Morphine and tramadol significantly increased pain latency in re-exposure. In case of tramadol, this increase was greater for single-dose compared to increasing-dose, while in case of morphine, this effect was greater for increasing-dose compared to single-dose. Conclusion: It seems that analgesic effect of re-exposure to tramadol in perepubertal rats is more than morphine and morphine's effect in the neonatal has a greater dose-dependency. Changes in the brain systems evolution influenced by exposure to these drugs and different functional mechanisms of morphine and tramadol are probably the basis for these results.

Keywords: Morphine, Tramadol, Perepubertal, Chronic, Hot plate

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