The Effect of Ciprofloxacin and Gentamicin on Spinal Morphine-Induced Antinociception in Rats*

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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; P0.05). This was reversed with intraperitoneal naloxone (P0.05). 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.