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Background: The antidepressant amitriptyline, the inhibitor of microglia activation minocycline, and the neurokinin-1 antagonist maropitant have all been used to prevent or treat hyperalgesia and opioid tolerance., Objectives: To determine the effect of amitriptyline, minocycline, maropitant, independently or with remifentanil, on the sevoflurane minimum alveolar concentration in rats and whether these drugs may block opioid-induced hyperalgesia and acute opioid tolerance under inhalational anaesthesia., Design: A randomised, laboratory study., Setting: Experimental Unit, La Paz University Hospital, Madrid, Spain., Animals: One hundred and fourteen adult male Wistar rats., Interventions: Intraperitoneal administration of amitriptyline (10 and 50  mg  kg-1), minocycline (30 and 100  mg  kg-1), maropitant (10 and 30 mg  kg-1) or isotonic saline, combined with a constant rate intravenous infusion of remifentanil (240 μg  kg-1  h-1) or saline., Main Outcome Measures: Sevoflurane minimum alveolar concentration was determined before and after administration of the drugs; acute opioid tolerance was defined as a decreased ability of remifentanil to reduce the minimum alveolar concentration in the short term. In addition, mechanical nociceptive thresholds were determined before and after these treatments. Opioid-induced hyperalgesia was defined as an increase in mechanical nociceptive thresholds after opioid administration., Results: Amitriptyline, minocycline and maropitant reduced minimum alveolar concentration up to 24 (8)%, 23 (6)% and 15 (5)%, respectively (P <0.001). Remifentanil alone reduced minimum alveolar concentration by 36 (6)% (P <0.001), and in combination with amitriptyline, minocycline and maropitant, the reduction was 76 (9)%, 75 (16)% and 59 (5)%, respectively (P <0.001). An acute tolerance effect (P < 0.01) and a decrease in the mechanical nociceptive thresholds were observed with remifentanil in all groups., Conclusion: Amitriptyline, minocycline and maropitant reduced the minimum alveolar concentration and potentiated the remifentanil minimum alveolar concentration reduction but failed to block opioid-induced hyperalgesia and acute opioid tolerance.

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.