Time dependent antinociceptive effects of morphine and tramadol in the hot plate test: Using different methods of drug administration in female rats

Morphine and tramadol which have analgesic effects can be administered acutely or
chronically. This study tried to investigate the effect of these drugs at various times by using
different methods of administration (intraperitoneal, oral, acute and chronic). Sixty adult
female rats were divided into six groups. They received saline, morphine or tramadol (20 to
125 mg/Kg) daily for 15 days. A hot plate test was performed for the rats at the 1st, 8th and 15th
days. After drug withdrawal, the hot plate test was repeated at the 17th, 19th, and 22nd days. There
was a significant correlation between the day, drug, group, and their interaction (P<0.001). At
1st day (d1), both morphine, and tramadol caused an increase in the hot plate time comparing
to the saline groups (P<0.001), while there was no correlation between drug administration
methods of morphine and/or tramadol. At the 8th day (d8), morphine and tramadol led to the
most powerful analgesic effect comparing to the other experimental days (P<0.001). At the
15th day (d15), their effects diminished comparing to the d8. After drug withdrawal, analgesic
effect of morphine, and tramadol disappeared. It can be concluded that the analgesic effect of
morphine and tramadol increases with the repeated use of them. Thereafter, it may gradually
decrease and reach to a level compatible to d1. The present data also indicated that although the
analgesic effect of morphine and tramadol is dose-and-time dependent, but chronic exposure to
them may not lead to altered nociceptive responses later in life