Potentiation by ketamine of fentanyl antinociception. I. An experimental study in rats showing that ketamine administered by non-spinal routes targets spinal cord antinociceptive systems.

Abstract

Background. Ketamine has been found to exert antinociceptive effects in animals and to be analgesic at subanaesthetic doses in humans. This study was designed to investigate the involvement of spinal cord mechanisms in the potentiation of opioid analgesia by parenteral non-spinal administration of ketamine. Methods. Thresholds for nociception were measured in an acute pain model in rats that allowed identification of antinociceptive effects due to drug action in the spinal cord. Dose-response curves for the antinociceptive effects of ketamine alone and ketamine in conjunction with the mu opioid fentanyl were constructed. Results. Intraperitoneal ketamine up to 3.75 mg kg-1 caused no sedative or antinociceptive effects and intrathecal ketamine caused dose-dependent, spinally mediated antinociceptive effects. Injections of ketamine doses that caused no antinociceptive effects when given alone (intrathecal 25 mug and intraperitoneal 3.75 mg/kg) significantly increased spinally mediated antinociception produced by intrathecal fentanyl injections when assessed using noxious heat (tail-flick test) but not when assessed by noxious electrical current (electrical current threshold test). Conclusions. We conclude that ketamine can potentiate the effects of fentanyl by an interaction at the level of the spinal cord even when ketamine is given via a non-spinal route of administration.