Antinociceptive effects of combining low doses of neuroleptic drugs and fentanyl in sheep.

Effects of low doses of the neuroleptic drugs droperidol and zuclopenthixol, combined with a subanalgesic dose of the opioid mu-agonist, fentanyl, on mechanical nociceptive thresholds were evaluated in sheep. Intravenously administered droperidol (5 micrograms/kg of body weight) did not induce any change in the nociceptive thresholds when administered alone, but caused marked increase in threshold responses when combined with a subanalgesic dose of fentanyl (5 micrograms/kg). Similarly, a combination of i.v. administered zuclopenthixol (100 micrograms/kg) and fentanyl induced significant (P < 0.05) antinociceptive effects, whereas zuclopenthixol administered i.v. alone had no effect on the threshold responses. Intrathecal administration of a low dose of droperidol (5-micrograms total dose) combined with i.v. administered fentanyl also increased mechanical thresholds significantly (P < 0.05). These results indicate that interactions exist between dopaminergic and opioid systems in the processing of nociceptive information and that these effects may, at least partially, be mediated spinally.