Exogenous gaseous superoxide potentiates the antinociceptive effect of opioid analgesic agents.

The study examined the potentiation of the antinociceptive action of opioid analgesics produced by gaseous superoxide (GS) in the rat hind paw withdrawal test (PWT) and by GS or hydrogen peroxide (HP) in the formalin test. In the PWT, inhalation of GS for 50 minutes before i.p. injection of threshold doses of morphine (0.5mg/kg) and trimeperidine (1.0 mg/kg) increased the threshold of nociception (TN) by a maximum of 43.0% (p<0.05) and 113.4% (p<0.01) respectively. The GS/trimeperidine-dependent increase in TN showed two peaks, the second of which could be suppressed by nialamide. Naloxone abolished the GS/morphine-dependent increased in the TN. In the formalin test, a significant antinociceptive effect developed after GS inhalation or HP administration (intranasally, 2×5μl of 2×10−5 mol/l solution in saline) in combination with low doses of Omnopon (0.06–0.75 mg/kg). These results suggest that both GS and HP potentiate the antinociceptive effects of opioid analgesics.