Analgesic synergy and improved motor function produced by combinations of mu-delta- and mu-kappa-opioids.

This study evaluated the effects of intrathecal administration of a low-analgesic dose of the selective mu-agonist DAMGO co-administered with sequentially increasing doses of either the selective delta-agonist DPDPE or the selective kappa-agonist, U50,488H on mechanical nociceptive thresholds in the rat. Potent analgesic synergy was observed with both combinations. Since an elevation in nociceptive threshold can result from motor deficits, as well as true analgesia, we also evaluated the effects of the combination regimens on motor coordination using a rotarod apparatus. The combination regimens produced significantly less motor deficits than those observed when DPDPE and U50,488H were administered as single agents. These findings of enhanced analgesia with decreased motor side-effects associated with administration of fixed mu/delta or mu/kappa combinations suggest that co-administration of opiates that act at different receptors may constitute a superior approach to the treatment of pain.