Nitric oxide synthase inhibition selectively potentiates swim stress antinociception in rats.

Since nitric oxide (NO) has been implicated in nociceptive processing, the present study examined whether NO synthase inhibition with either Nw-nitro-L-arginine (L-NA) or its methyl ester (L-NAME) would alter antinociception elicited by either continuous (CCWS) or intermittent cold-water swims (ICWS) on the tail-flick and jump tests. Whereas CCWS antinociception on both tests was significantly potentiated by a dose range of L-NA (0.1-4 mg/kg IP) and L-NAME (1 mg/kg IP), ICWS antinociception was largely unaffected by these manipulations. In contrast, administration of the less active D isomer (D-NAME) failed to alter CCWS antinociception and reduced ICWS antinociception. The ability of NO synthase inhibition to potentiate CCWS antinociception could not be explained by changes in CCWS hypothermia. Since ICWS antinociception is mediated by mu-opioid manipulations and CCWS antinociception is sensitive to delta-opioid and nonopioid manipulations, this indicates that NO synthase inhibition may be acting upon a selective form of pain inhibition.