Inhibition of nitric oxide synthase enhances morphine antinociception in the rat spinal cord.

NG-nitro-L-arginine methyl ester (L-NAME, 400-1500 micrograms), administered intrathecally (ith.), elicits a slight but dose-related antinociception in rats, assessed by tail-flick and paw pressure tests. L-NAME (400 micrograms) and morphine (0.5 microgram) coadministered ith. elicit a profound and long-lasting antinociception, which is abolished by ith. administration of 3-morpholino-sydnonimine (SIN-1, 100 micrograms). Hemoglobin (266 micrograms) administered ith. also slightly potentiates morphine antinociception. These results suggest that nitric oxide (NO) is involved in spinal nociceptive events, and that the increased production of NO following the nociceptive input may diminish the efficiency of opioid antinociception in the spinal cord.