title: The antinociceptive activity of intrathecally administered amiloride and its interactions with morphine and clonidine in rats.
abstract: In this study, we aimed to evaluate the antinociceptive interaction between intrathecally administered amiloride and morphine or clonidine. Using rats chronically implanted with lumbar intrathecal catheters, we examined the ability of intrathecal amiloride, morphine, clonidine, and mixtures of amiloride-morphine and amiloride-clonidine to alter tail-flick latency. To characterize any interactions, isobolographic analysis was performed. The effects of pretreatment with intrathecally administered naloxone or yohimbine were tested. Intrathecal administration of amiloride (25-150 μg), morphine (.25-10 μg), or clonidine (.5-10 μg) alone produced significant dose-dependent antinociception in the tail-flick test. The median effective dose (ED(50)) values for intrathecally administered amiloride, morphine, and clonidine were 120.5 μg, 5.0 μg, and 4.4 μg, respectively. Isobolographic analysis exhibited a synergistic interaction after coadministration of amiloride-morphine and amiloride-clonidine. Intrathecal pretreatment with naloxone (10 μg) completely blocked the antinociceptive effects of morphine and the amiloride-morphine mixture. Intrathecal pretreatment with yohimbine (20 μg) completely blocked the antinociceptive effect of clonidine and antagonized the effect of the amiloride-clonidine mixture. There was no motor dysfunction or significant change in blood pressure or heart rate after the intrathecal administration of amiloride, amiloride-morphine, and amiloride-clonidine. The synergistic effect observed after the coadministration of amiloride and morphine or clonidine suggests a functional interaction among calcium channels, μ-receptors and α(2)-receptors at the spinal cord level of the nociceptive processing system.
  
  
  CONCLUSIONS
  Although intrathecal morphine and clonidine produces pronounced analgesia, antinociceptive doses of intrathecal morphine and clonidine produce several side effects, including hypotension, bradycardia, sedation, and tolerance. This article presents antinociceptive synergistic interaction between amiloride and morphine, amiloride, and clonidine on thermal nociceptive tests in the rat.
authors.affiliation: Department of Anesthesiology, State Key Laboratory of Oncology on Southern China, Cancer Center, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Handong
authors.initials: H
authors.lastname: Ouyang
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Bai
authors.forename: Wan
authors.initials: W
authors.lastname: Huang
authors.forename: Dongtai
authors.initials: D
authors.lastname: Chen
authors.forename: Shuji
authors.initials: S
authors.lastname: Dohi
authors.forename: Weian
authors.initials: W
authors.lastname: Zeng
mesh_terms: D000584:Amiloride / Q000008:administration & dosage*; D000700:Analgesics / Q000008:administration & dosage*; D000818:Animals; D019540:Area Under Curve; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006339:Heart Rate / Q000187:drug effects; D006930:Hyperalgesia / Q000188:drug therapy / Q000503:physiopathology; D007278:Injections, Spinal; D008297:Male; D009020:Morphine / Q000008:administration & dosage*; D009043:Motor Activity / Q000187:drug effects; D010147:Pain Measurement / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D026941:Sodium Channel Blockers / Q000008:administration & dosage*; D013997:Time Factors
chemical_list: D000700:Analgesics; D026941:Sodium Channel Blockers; D009020:Morphine; D000584:Amiloride; D003000:Clonidine