Hyperbaric oxygen produces a nitric oxide synthase-regulated anti-allodynic effect in rats with paclitaxel-induced neuropathic pain

Research has demonstrated that hyperbaric oxygen (HBO₂) treatment produced relief of both acute and chronic pain in patients and animal models. However, the mechanism of HBO₂ antinociceptive effect is still elusive. Based on our earlier findings that implicate NO in the acute antinociceptive effect of HBO₂, the purpose of this study was to ascertain whether HBO₂-induced antinociception in a chronic neuropathic pain model is likewise dependent on NO. Neuropathic pain was induced in male Sprague Dawley rats by four injections of paclitaxel (1.0 mg/kg, i.p.). Twenty-four hours after the last paclitaxel injection, rats were treated for one day or four consecutive days with 60-min HBO₂ at 3.5 atmospheres absolute (ATA). Two days before HBO₂ treatment, some groups of rats were implanted with Alzet® osmotic minipumps that continuously infused a selective inhibitor of neuronal NO synthase (nNOS) into the lateral cerebral ventricle for 7 days. Mechanical and cold allodynia were assessed every other day, using electronic von Frey and acetone assays, respectively. Rats in the paclitaxel control group exhibited a mechanical or cold allodynia that was significantly reversed by one HBO₂ treatment for mechanical allodynia and four HBO₂ treatments for cold allodynic. In rats treated with the nNOS inhibitor, the effects of HBO₂ were nullified in the mechanical allodynia test but unaffected in the cold allodynia test. In summary, these results demonstrate that the antiallodynic effect of HBO₂ in two different pain tests is dependent on NO in the CNS.