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The Effect of Ciprofloxacin and Gentamicin on Spinal Morphine‐Induced Antinociception in Rats *
Author(s) -
Luger Thomas J.,
Farkas Wolfgang,
Geisler Hans,
Lorenz Ingo H.
Publication year - 2005
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/j.1742-7843.2005.pto_05.x
Subject(s) - in vivo , medicine , pharmacology , downregulation and upregulation , endothelium , inflammation , adhesion , cell adhesion molecule , intercellular adhesion molecule 1 , immunology , chemistry , endocrinology , biochemistry , biology , microbiology and biotechnology , organic chemistry , gene
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]μg; ED50 ciprofloxacin‐morphine=0.87 (CI 95% 0.68, 1.21) μg, P<0.05) and in the tail‐flick test (ED50 saline‐morphine=1.98 (CI 95%: 1.21, 2.84) μg; ED50 ciprofloxacin‐morphine=0.37 (CI 95%: 0.23, 0.44) μg; 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]μg; tail‐flick test: 0.82 (CI 95%: 0.52, 1.92) μg) 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) μg; tail‐flick test: ED50 gentamicin‐morphine=2.43 (CI 95%: 1.58; 5.22]μg; 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.