Amitriptyline, minocycline and maropitant reduce the sevoflurane minimum alveolar concentration and potentiate remifentanil but do not prevent acute opioid tolerance and hyperalgesia in the rat. Issue 4 (April 2015)

• Record Type: Journal Article
• Authors: Aguado, Delia; Abreu, Mariana; Benito, Javier; García-Fernández, Javier; Gómez de Segura, Ignacio A.
• Is Part Of: European journal of anaesthesiology. Volume 32:Issue 4(2015:Apr.)
• Publication Date: 2015-04
• Subjects: Anesthesiology -- Periodicals; Anesthesiology -- Periodicals; Anesthésiologie -- Périodiques; Anesthesiology; Periodicals; Electronic journals; 617.96
• DOI: 10.1097/EJA.0000000000000098
• Languages: English
• ISSNs: 0265-0215

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <title>BACKGROUND</title> <p>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.</p> </sec> <sec> <title>OBJECTIVES</title> <p>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.</p> </sec> <sec> <title>DESIGN</title> <p>A randomised, laboratory study.</p> </sec> <sec> <title>SETTING</title> <p>Experimental Unit, La Paz University Hospital, Madrid, Spain.</p> </sec> <sec> <title>ANIMALS</title> <p>One hundred and fourteen adult male Wistar rats.</p> </sec> <sec> <title>INTERVENTIONS</title> <p>Intraperitoneal administration of amitriptyline (10 and 50 mg kg<sup>−1</sup>), minocycline (30 and 100 mg kg<sup>−1</sup>), maropitant (10 and 30 mg kg<sup>−1</sup>) or isotonic saline, combined with a constant rate intravenous infusion of remifentanil (240 μg kg<sup>−1</sup> h<sup>−1</sup>) or saline.</p> </sec> <sec> <title>MAIN OUTCOME MEASURES</title> <p>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.</p> </sec> <sec> <title>RESULTS</title> <p>Amitriptyline, minocycline and maropitant reduced minimum alveolar concentration up to 24 (8)%, 23 (6)% and 15 (5)%, respectively (<italic>P</italic> <0.001). Remifentanil alone reduced minimum alveolar concentration by 36 (6)% (<italic>P</italic> <0.001), and in combination with amitriptyline, minocycline and maropitant, the reduction was 76 (9)%, 75 (16)% and 59 (5)%, respectively (<italic>P</italic> <0.001). An acute tolerance effect (<italic>P</italic> < 0.01) and a decrease in the mechanical nociceptive thresholds were observed with remifentanil in all groups.</p> </sec> <sec> <title>CONCLUSION</title> <p>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.</p> </sec> </abstract>