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

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.