title: Antinociceptive and motor effects of intrathecal morphine combined with intrathecal clonidine, noradrenaline, carbachol or midazolam in rats.
abstract: This study investigated antinociceptive effects of intrathecal morphine combined with intrathecal clonidine, noradrenaline, carbachol or midazolam in rats. Each animal received intrathecally, on 3 separate occasions (i) 2 micrograms morphine (M), (ii) a dose (D) of one of the non-opioid drugs, and (iii) a combination, 1/2(M+D), consisting of 1 microgram morphine plus half the dose of the non-opioid drug. Antinociceptive effects were assessed by the hot-plate and tail-flick tests over the duration of drug action. All non-opioid drugs studied led to dose-related antinociceptive effects when given alone. Addition of morphine caused a left shift in the dose-response curves of all the non-opioid drugs, indicating at least some degree of additive effects. Effects were considered supra-additive when the effect of the combination, 1/2(M+D), was significantly greater than both the effect of 2 micrograms morphine and the dose of non-opioid. Evidence of supra-additive antinociceptive effects was obtained only with the clonidine-morphine combination.
authors.affiliation: Pain Management Unit, Flinders Medical Centre, Bedford Park, S.A. 5042 Australia.
authors.forename: John L
authors.initials: JL
authors.lastname: Plummer
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Cmielewski
authors.forename: Geoffrey K
authors.initials: GK
authors.lastname: Gourlay
authors.forename: Harry
authors.initials: H
authors.lastname: Owen
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Cousins
mesh_terms: D000700:Analgesics / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology; D004357:Drug Synergism; D007278:Injections, Spinal; D008297:Male; D008874:Midazolam / Q000494:pharmacology; D009020:Morphine / Q000008:administration & dosage* / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects*; D009619:Nociceptors / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D000700:Analgesics; D009020:Morphine; D002217:Carbachol; D003000:Clonidine; D008874:Midazolam; D009638:Norepinephrine