The selective role of nitric oxide in opioid-mediated footshock stress antinociception in mice

Different kinds of stress induce distinct antinociceptive properties that may be related or unrelated to the endogenous opioid system. Nitric oxide (NO) has been implicated in stress-activated mechanisms. NO also plays an important role in the modulation of nociceptive responses and has many functional interactions with opioidergic pathways. The present study examined the role of NO in two distinct opioid-mediated and nonopioid types of antinociception induced by footshock stress and assessed by the tail flick latency in mice. Brief and continuous footshock (3 min) induced a naloxone-insensitive antinociception that was not altered by either l-NAME (10 mg/kg), aminoguanidine (100 mg/kg) or l-arginine (60 mg/kg). In contrast, prolonged and intermittent footshock (30 min) induced a naloxone-reversible antinociceptive effect that was blocked by l-NAME (2–10 mg/kg) but not by aminoguanidine (100 mg/kg). l-Arginine (20 and 60 mg/kg) also did not alter this type of antinociception. Morphine (1 mg/kg) induced a mild antinociceptive effect in nonstressed animals that was potentiated by l-NAME (2 mg/kg) but not affected by aminoguanidine (100 mg/kg). The same dose of morphine increased the antinociceptive effect of prolonged and intermittent footshock but this increase was inhibited by l-NAME (2 mg/kg) but not by aminoguanidine. In conclusion, NO of constitutive origin is selectively involved in an opioid-mediated type of footshock stress antinociception in mice.