Direct spinal effect of intrathecal acetaminophen on visceral noxious stimulation in rabbits

The aim of this study was to investigate the effect of intrathecal acetaminophen on visceral and somatic noxious stimulation in the intact, non-anesthetized rabbit. Sixteen rabbits had intrathecal catheters implanted surgically. Visceral noxious stimulation was induced by intestinal distension of the distal colon and somatic stimulation with increasing electrical current through skin electrodes placed in either the cervical or the lumbar area. The effect on visceral noxious stimulation was assessed following intrathecal injection of 0.5, 2.5 and 5 mg of acetaminophen and following 10 and 50 mg acetaminophen intravenously. Naloxone 0.2 mg and yohimbine 0.1 mg were administered intrathecally prior to intrathecal injection of acetaminophen 5 mg. A dose-dependent effect of intrathecal acetaminophen against the visceromotor reflex produced by intestinal distension was shown. No effects on thresholds to lumbar or cervical electrical stimulation or intestinal distension were observed following i.v. administration. Thresholds to noxious electrical stimulation were only significantly elevated at the lumbar level following i.t. injection of 5 mg acetaminophen. Naloxone failed to antagonize the effect of intrathecal acetaminophen, whereas intrathecal yohimbine attenuated the effect of intrathecal acetaminophen in both tests. In conclusion, a spinal, dose-dependent, naloxone-irreversible, and yohimbine-reversible effect of intrathecal acetaminophen on electrical and visceral noxious stimulation was demonstrated.