Role of nitric oxide (NO) in the hyperbaric oxygen (HBO2)‐induced long‐lasting activation of endogenous opioid systems in mice

Abstract

Exposure to HBO2 causes a long‐lasting analgesic effect in patients with chronic pain (Kiralp et al., J. Int. Med. Res. 32:258–262, 2004). To determine the duration of antinociceptive effect in an animal model following exposure to HBO2, male NIH Swiss mice (20–30 g) were exposed to HBO2 at 2.5 ATA for 60 min then removed to room air for varying durations of time (5, 15, 30, 60, 90, 120, 150 or 180 min) prior to antinociceptive testing. The antinociceptive effect of HBO2 remained robust up to 90 min but subsided by 120 min. By contrast, mice exposed to 70% nitrous oxide for 60 min exhibited antinociception only through the 15‐min interval. When administered prior to HBO2 exposure, both naltrexone and L‐NAME antagonized the antinociceptive effect seen 90 min later. When administered prior to antinociceptive testing, naltrexone but not L‐NAME antagonized the antinociceptive effect of HBO2. These results suggest that there is a critical role of NO during HBO2 exposure that is required for expression of the opioid‐mediated antinociceptive effect 90 min later. (Supported in part by NIH Grant GM‐77153, ASPET SURF Program and the Chico Hyperbaric Center).