title: The effect of ciprofloxacin and gentamicin on spinal morphine-induced antinociception in rats.
abstract: This paper investigates the possible antinociceptive effect of systemically administered ciprofloxacin and gentamicin and its influence on intrathecal morphine-induced antinociception. Using thermal nociceptive tests (hot-plate test and tail-flick test) and a motor function test (catalepsy test) in male Sprague-Dawley rats (n=5-9/dose), the following observations were made: ciprofloxacin administered intraperitoneally in the dose range 4-64 mg/kg demonstrated a modest antinociceptive effect in both nociceptive tests. Solvent of ciprofloxacin (intraperitoneally) and saline (intraperitoneally), given as a control, showed no effect. Gentamicin, administered at a dose of 0.1-4 mg/kg intraperitoneally, demonstrated a significant (P<0.05) antinociceptive effect in the tail-flick test but not in the hot-plate test. However, opioid antagonists caused no significant change in the antibiotics. Furthermore, ciprofloxacin intraperitoneally produced a significant left-shift in the hot-plate test (ED50 saline-morphine=2.86 [CI 95%: 2.2, 4.32]microg; ED50 ciprofloxacin-morphine=0.87 (CI 95% 0.68, 1.21) microg, P<0.05) and in the tail-flick test (ED50 saline-morphine=1.98 (CI 95%: 1.21, 2.84) microg; ED50 ciprofloxacin-morphine=0.37 (CI 95%: 0.23, 0.44) microg; P<0.05) for intrathecal morphine-induced antinociception. From a comparison of these data with the predicted ciprofloxacin-morphine value (hot-plate test: 1.61 (CI 95%: 1.18, 2.51]microg; tail-flick test: 0.82 (CI 95%: 0.52, 1.92) microg) we estimate that ciprofloxacin and morphine produce at least additive effects (P>0.05). This was reversed with intraperitoneal naloxone (P<0.05). Gentamicin intraperitoneally did not influence the antinociception achieved with intrathecal administration of morphine (hot-plate test: ED50 gentamicin-morphine=2.71 (CI 95%: 2.35; 3.2) microg; tail-flick test: ED50 gentamicin-morphine=2.43 (CI 95%: 1.58; 5.22]microg; P>0.05). These data show that intraperitoneal administration of ciprofloxacin and gentamicin produces a modest antinociceptive effect in the hot-plate test and tail-flick test. Ciprofloxacin, but not gentamicin, can interact at least additively to increased naloxone-reversible morphine intrathecal antinociception. Differences in the ability to penetrate the blood-brain barrier between the two antibiotics could explain the lack of effect from gentamicin in the hot plate and on morphine-induced antinociception.
authors.affiliation: Department of Anaesthesiology and Critical Care Medicine, Innsbruck Medical University, 6620 Innsbruck, Austria. thomas.luger@uibk.ac.at
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Luger
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Farkas
authors.forename: Hans
authors.initials: H
authors.lastname: Geisler
authors.forename: Ingo H
authors.initials: IH
authors.lastname: Lorenz
mesh_terms: D000700:Analgesics / Q000627:therapeutic use*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002939:Ciprofloxacin / Q000627:therapeutic use*; D004357:Drug Synergism; D005260:Female; D005839:Gentamicins / Q000627:therapeutic use*; D007274:Injections, Intraperitoneal; D007278:Injections, Spinal; D009020:Morphine / Q000627:therapeutic use*; D009043:Motor Activity / Q000187:drug effects; D009270:Naloxone / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy*; D010147:Pain Measurement; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000700:Analgesics; D005839:Gentamicins; D009270:Naloxone; D002939:Ciprofloxacin; D009020:Morphine