Subeffective doses of dexketoprofen trometamol enhance the potency and duration of fentanyl antinociception

The combination of classic non-steroidal antiinflammatory drugs (NSAIDs) with opiates induces more analgesia than the summed effect of each drug given separately. No studies have been performed using new generation NSAIDs and fentanyl nor on the duration of this effect. We have studied the analgesic effect of fentanyl alone and after the administration of subeffective doses of dexketoprofen trometamol in rat nociceptive responses. The responses were evoked by noxious mechanical stimulation and were recorded as single motor units in male Wistar rats anaesthetized with alpha-chloralose. The effective dose 50 (ED(50)) observed with fentanyl was 22.4 +/- 1.5 microg kg(-1) and full recovery was apparent 20 min later. The administration of a total dose of 40 microg kg(-1) of dexketoprofen trometamol did not induce any significant effect on the nociceptive responses. In the presence of dexketoprofen trometamol, the ED(50) for fentanyl was 5 fold lower than before: 3.8 +/- 1.1 microg kg(-1) and no significant recovery was observed 45 min later. The opioid antagonist naloxone (200 microg kg(-1)) did not reverse the effect, although in control experiments the same dose was able to prevent any action of fentanyl given alone. We conclude that the combination of fentanyl and subeffective doses of dexketoprofen trometamol induces a more potent and longer lasting analgesic effect than that observed with fentanyl alone, and that this is not an opioid mediated action.