Low doses of nitroparacetamol or dexketoprofen trometamol enhance fentanyl antinociceptive activity

Abstract

We have reported that subeffective doses of the nonsteroidal anti-inflammatory drug (NSAID) dexketoprofen trometamol enhances μ-opioid receptor agonist fentanyl antinociception. The aim of this study was to assess if this effect can also be observed with other new cyclooxygenase-inhibitors such as nitroparacetamol, and in responses to high intensity electrical stimulation (wind-up). Single motor units were recorded in male Wistar rats under α-chloralose anaesthesia. The antinociceptive effect of fentanyl was studied alone and in the presence of subeffective doses of dexketoprofen trometamol or nitroparacetamol. In responses to noxious mechanical stimulation, the potency of fentanyl was enhanced by more than threefold in the presence of the NSAIDs and no significant recovery was observed after 45 min. The opioid antagonist naloxone and the α 2-adrenoceptor antagonist atipamezol did not reverse the effect. The enhancement of the effect of fentanyl in wind-up was lower though significant. We conclude that the co-administration of subeffective doses of new cyclooxygenase-inhibitors and the μ-opioid receptor agonist fentanyl should be considered as a potential pain therapy.