A Prolonged Nitric Oxide-Dependent, Opioid-Mediated Antinociceptive Effect of Hyperbaric Oxygen in Mice

Abstract 

Hyperbaric oxygen (HBO₂) therapy is reported to cause pain relief in several conditions of chronic pain. A single 60-minute session of HBO₂ treatment produced a prolonged antinociceptive effect in mice that persisted for 90 minutes after cessation of treatment. The HBO₂-induced antinociception was significantly attenuated by pretreatment before HBO₂ exposure with the opioid antagonist naltrexone, the nonspecific nitric oxide synthase (NOS)-inhibitor N^G-nitro-l-arginine methyl ester (L-NAME), and the selective neuronal NOS-inhibitor S-methyl-l-thiocitrulline (SMTC) but not the selective endothelial NOS-inhibitor N⁵-(1-iminoethyl)-l-ornithine (L-NIO). The antinociception was also significantly reduced by central pretreatment with a rabbit antiserum against dynorphin_1-13 but not by rabbit antisera against either β-endorphin or methionine-enkephalin. The prolonged antinociceptive effect at 90 minutes after HBO₂-induced treatment was also significantly attenuated by naltrexone but not L-NAME administered 60 minutes after HBO₂ treatment but before nociceptive testing. These findings indicate that the antinociception that persists for 90 minutes after HBO₂ exposure is mediated by nitric oxide (NO) and opioid mechanisms but that the NO involvement is critical during the HBO₂ treatment and not at the time of nociceptive testing. These results are consistent with the concept that HBO₂ may induce an NO-dependent release of opioid peptide to cause a long-acting antinociceptive effect.

Perspective

This article presents evidence of a persistent antinociceptive effect of hyperbaric oxygen treatment that is mediated by opioid and NO mechanisms. Further elucidation of the underlying mechanism could identify molecular targets to cause a longer-acting activation of endogenous pain-modulating systems.

Key words: Hyperbaric oxygen, nitric oxide, opioid, antinociception, mice