Differential effects of SKF 38393 and LY 141865 on nociception and morphine analgesia.

The effects of SKF 38393 and LY 141865 on nociceptive sensitivity and morphine-induced analgesia were compared. SKF 38393 administered to mice either peripherally or centrally was without effect on either base line response latencies or morphine's analgesia. By contrast, s.c. injections of LY 141865 resulted in a dose-related hyperalgesia. A paradoxical analgesia was observed when LY 141865 was given intracerebroventricularly. Both the analgesia and hyperalgesia were antagonized by sulpiride but remained unaffected by the opioid antagonist Mr-1452. Central and peripheral pretreatment with LY 141865 resulted in respective enhancement and attenuation in the analgesic activity of morphine. The present results would indicate that D-2 receptors may be involved in nociception and analgesic mechanisms. In addition it suggests that D-2 receptors may exert both inhibitory and facilitatory influences on nociceptive and analgesic mechanisms.