Tramadol-induced hyperalgesia and its prevention by ketamine in rats A randomised experimental study

BACKGROUNDOpioid analgesia not only reduces inhalational anaesthetic requirements but may also induce delayed hyperalgesia, with potential effects on the minimum alveolar concentration (MAC) of inhalational anaesthetics.OBJECTIVESThe objective of this study was to evaluate the development of tramadol-induced hyperalgesia and the associated changes in MAC, and whether ketamine prevents both processes.DESIGNA randomised, experimental study.SETTINGExperimental Surgery Unit, La Paz University Hospital, Madrid, Spain.ANIMALSThirty-nine adult male Wistar rats.INTERVENTIONSMechanical nociceptive thresholds (MNT) were determined up to 21 days after the intraperitoneal administration of a single dose of tramadol (50mgkg(-1)) with or without ketamine (10mgkg(-1)), or 0.9% saline. The MNT and the MAC of sevoflurane were also assessed in a second experiment before, early (30min) and 7 days after drug administration with the same treatments.MAIN OUTCOME MEASURESThe MAC and MNT were evaluated. The analysis of variance (ANOVA) test was employed to determine differences between treatments and times on MAC and MNT.RESULTSTramadol, alone or combined with ketamine, produced an early increase in MNT. However, tramadol given alone decreased MNT from day 1 up to 3 weeks, which was associated with an increase in the MAC of sevoflurane (P<0.05; day 7). Ketamine administration prevented both the reduction in MNT and the increase in MAC (P>0.05).CONCLUSIONTramadol-induced hyperalgesia in the rat lasted for several weeks and was associated with an increase in the MAC of sevoflurane. Prior administration of ketamine blocked both phenomena.