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

BACKGROUND: Opioid 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. OBJECTIVES: The 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. DESIGN: A randomised, experimental study. SETTING: Experimental Surgery Unit, La Paz University Hospital, Madrid, Spain. ANIMALS: Thirty-nine adult male Wistar rats. INTERVENTIONS: Mechanical nociceptive thresholds (MNT) were determined up to 21 days after the intraperitoneal administration of a single dose of tramadol (50 mg kg−1) with or without ketamine (10 mg kg−1), or 0.9% saline. The MNT and the MAC of sevoflurane were also assessed in a second experiment before, early (30 min) and 7 days after drug administration with the same treatments. MAIN OUTCOME MEASURES: The MAC and MNT were evaluated. The analysis of variance (ANOVA) test was employed to determine differences between treatments and times on MAC and MNT. RESULTS: Tramadol, 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). CONCLUSION: Tramadol-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.

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