Hyperbaric oxygen (HBO2) therapy induces analgesia in various conditions of pain in humans. In mice, HBO2 treatment evokes an acute antinociceptive response in the abdominal constriction test. To demonstrate the dependence of HBO2-induced antinociception on nitric oxide (NO), antinociceptive responsiveness to HBO2 was assessed after three different approaches that interfered with NO production. HBO2-induced antinociception was significantly attenuated by intracerebroventricular and intrathecal pretreatment with an inhibitor of NO synthase (NOS) enzyme and also by an antisense oligodeoxynucleotide directed against neuronal NOS. The antinociceptive effect was also significantly reduced in mice homozygous for a defective neuronal NOS gene. On the basis of these results, we conclude that neuronal NO is critical in the expression of the acute antinociceptive effect of HBO2.

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).

HBO2 treatment is reportedly effective in alleviating various chronic pain conditions (Yildiz et al., Curr. Pain Headache Rep. 10:95–100, 2006). To investigate the mechanism of action, male NIH Swiss mice (20–30 g) were exposed to HBO2 (100% O2 @ 2.5 ATA) and assessed for antinociceptive responsiveness using the glacial acetic acid abdominal constriction test conducted in a small animal hyperbaric chamber. This 10‐min exposure evoked a robust antinociceptive effect during the HBO2 exposure. The magnitude of the HBO2‐induced antinociceptive was significantly reduced by pretreatment with naloxone and L‐NAME and partly antagonized by pretreatment with an antiserum against rat dynorphin. By comparison, the magnitude of antinociceptive effect of 70% N2O was significantly attenuated by pretreatment with naloxone, L‐NAME and dynorphin antiserum. These results indicate that HBO2–induced antinociception has commonalities with N2O. HBO2, similar to N2O, seems to evoke an NO‐dependent, opioid receptor‐mediated antinociceptive effect that may involve a different endogenous opioid peptide. (Supported in part by NIH Grant GM‐77153, ASPET SURF Program and the Chico Hyperbaric Center).

Exposure to 3.5 ATA HBO2 causes antinociception in mice (Ohgami et al., NeuroReport 20:1325, 2010). However, breathing O2 at an elevated pressure can potentially cause oxygen toxicity. The aim of this study was to identify the determinants of HBO2 antinociception and the toxicity profile of HBO2. Male NIH Swiss mice were assessed for acute antinociceptive responsiveness under room air or 100% O2 at 1.0 or 3.5 ATA, using the acetic acid‐induced abdominal constriction test. Only the combination of 100% O2 and 3.5 ATA caused significant antinociception. The antinociceptive effect of 100% O2 was pressure‐dependent up to 3.5 ATA. Oxygen toxicity was assessed by analyzing the levels of two oxidative stress markers, MDA (malondialdehyde) and protein carbonyl, in brain, spinal cord and lung after HBO2 exposure. The results showed no significant increase of either marker in the tested tissues, indicating an absence of significant oxidative stress caused by an 11‐min HBO2 treatment. In fact, even a 60‐min HBO2 treatment failed to produce any significant changes. It is concluded that HBO2 at 3.5 ATA is able to produce significant antinociception without causing oxygen toxicity in mice. (This research was supported by NIH Grant AT‐007222 and the Allen I. White Distinguished Professorship at Washington State University.)