Hyperalgesia and increased sevoflurane minimum alveolar concentration induced by opioids in the rat: a randomised experimental study.

ABSTRACT

BACKGROUND: Perioperative opioids reduce inhalational anaesthetic requirements. The initial hypoalgesia may, however, be followed by a rebound hyperalgesia. OBJECTIVES: To determine whether prior opioid administration influences inhalational anaesthetic requirements, which might be associated with opioid-induced hyperalgesia. DESIGN: A prospective, randomised, experimental study. SETTING: Experimental Surgery, La Paz University Hospital, Madrid, Spain. ANIMALS Seventy-nine adult male Wistar rats. INTERVENTIONS: Sevoflurane minimum alveolar concentration (MAC) and mechanical nociceptive thresholds (MNTs) were assessed at baseline and 7 days later following opioid treatment with remifentanil 120 µg  kg-1  h-1, buprenorphine 150 µg kg-1, methadone 8 mg  kg-1 or morphine 10 mg  kg-1 The duration of the effect of remifentanil on MAC and MNT was evaluated in addition to the preventive effect of ketamine 10 mg  kg-1 on remifentanil-induced hyperalgesia. MAIN OUTCOME MEASURES: The effect of different opioid treatments on MAC and MNT was evaluated using analysis of variance (ANOVA). RESULTS: All studied opioids produced an immediate reduction in sevoflurane MAC, followed by an increase (16%) in baseline MAC 7 days later (P < 0.05), although the immediate MAC reduction produced by these opioids at that time was not different. Remifentanil produced a decrease in MNT (P < 0.05), which was associated with an increase in the MAC (P < 0.05) that persisted at 21 days. The effect of remifentanil on MNT and MAC was blocked by ketamine. CONCLUSION: Opioid-induced hyperalgesia was associated with an increase in the MAC in normal rats who had not undergone surgery. Both effects lasted 21 days and were prevented by ketamine.