(+)-Morphine attenuates the (-)-morphine-produced tail-flick inhibition via the sigma-1 receptor in the mouse spinal cord.

We have previously demonstrated that pretreatment with (+)-morphine given intrathecally attenuates the intrathecal (-)-morphine-produced tail-flick inhibition. The phenomenon has been defined as antianalgesia against (-)-morphine-produced analgesia. Present experiments were then undertaken to determine if the antianalgesic effect induced by (+)-morphine given spinally is mediated by the stimulation of the sigma-1 receptor in the mouse spinal cord. Sigma-1 receptor ligands, N-[2-(3,4-Dichlorophenyl)ethyl]-N-methyl-2-(dimethylamino)ethylamine dihydrobromide (BD1047) and (+)-pentazocine were used to determine if (+)-morphine-induced antianalgesia is mediated by the stimulation of sigma-1 receptors in the mouse spinal cord. Tail-flick test was employed to measure the nociceptive response. All compounds were given intrathecally. Pretreatment with BD1047 (1-10 μg) or (+)-pentazocine (0.1-10 μg) dose-dependently reversed the attenuation of the (-)-morphine-produced tail-flick inhibition induced by (+)-morphine (10 pg). BD1047 and (+)-pentazocine injected alone did not affect (-)-morphine-produced tail-flick inhibition. The finding indicates that (+)-morphine attenuates the (-)-morphine-produced tail-flick inhibition via the activation of the sigma-1 receptors in the mouse spinal cord. Sigma-1 receptors may play an important role in opioid analgesia in the mouse spinal cord.