Modulators of pain in the spinal cord.

Intrathecal injection of subanalgesic doses of morphine (7.5 nmol) and dynorphin-A-(1-13) (1.25 nmol) in combination resulted in a marked analgesic effect as assessed by tail flick latency in the rat. The analgesic effect of the composite of dynorphin/morphine was dose-dependent in serial dilutions and not accompanied by any signs of motor dysfunction. Synergism between dynorphin and morphine can also be demonstrated without motor dysfunction, when dynorphin is injected together intrathecally with a serial increasing dosages of morphine. Metenkephalin showed an analogous synergistic effect with dynorphin and also morphine in the spinal cord, although dynorphin (and also metenkephalin) antagonized morphine analgesia by the intraventricular route. The underlying mechanism of the interactions among different classes of opioid ligands at different levels of the central nervous system deserves further study.