Effect of hyperbaric oxygen on chemotherapy-induced neuropathy in male and female rats.

Chemotherapeutic agents can cause peripheral neuropathy, a deleterious side effect of cancer treatment. Hyperbaric oxygen (HBO2) treatment has shown great potential for decreasing pain in numerous clinical pain conditions and in preclinical studies. This study was designed to test whether HBO2 might also be useful for treating chemotherapy-induced peripheral neuropathy. Male and female Sprague-Dawley rats were injected with 1 mg/kg paclitaxel or vehicle every other day for 7 days to induce allodynia, followed by either one single, or four daily 60-min exposures to HBO2 or room air. Mechanical and cold allodynia as well as locomotor behavior and body weight were assessed intermittently for several weeks. Estrous cycling was also tracked in female rats. Paclitaxel caused pronounced mechanical allodynia in both sexes that was completely reversed by either one or four treatments of HBO2. Females in all treatment groups showed greater cold acetone scores than males, and acetone scores were not reliably reduced by HBO2 treatment. Neither paclitaxel nor HBO2 treatment altered locomotor behavior or estrous cycling. We conclude that HBO2 treatment was highly effective at reducing mechanical allodynia in paclitaxel-treated rats without affecting weight gain, locomotion, or estrous cycling, suggesting that HBO2 may be effective for treating chemotherapy-induced neuropathic pain without producing significant side effects.

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.

Role of spinal GABA receptors in the acute antinociceptive response of mice to hyperbaric oxygen.

New pain treatments are in demand due to the pervasive nature of pain conditions. Hyperbaric oxygen (HBO2) has shown potential in treating pain in both clinical and preclinical settings, although the mechanism of this effect is still unknown. The aim of this study was to investigate whether the major inhibitory neurotransmitter γ-aminobutyric acid (GABA) is involved in HBO2-induced antinociception in the central nervous system (CNS). To accomplish this goal, pharmacological interactions between GABA drugs and HBO2 were investigated using the behavioral acetic acid abdominal constriction test. Western blotting was used to quantify protein changes that might occur as a result of the interactions. GABAA but not GABAB receptor antagonists dose-dependently reduced HBO2 antinociception, while antagonism of the GABA reuptake transporter enhanced this effect. Western blot results showed an interaction between the pain stimulus and HBO2 on expression of the phosphorylated ß3 subunit of the GABAA receptor at S408/409 in homogenates of the lumbar but not thoracic spinal cord. A significant interaction was also found in neuronal nitric oxide synthase (nNOS) expression in the lumbar but not thoracic spinal cord. These findings support the notion that GABA may be involved in HBO2-induced antinociception at the GABAA receptor but indicate that more study will be needed to understand the intricacies of this interaction.

Hyperbaric oxygen treatment suppresses withdrawal signs in morphine-dependent mice.

Hyperbaric oxygen (HBO2) therapy reportedly reduces opiate withdrawal in human subjects. The purpose of this research was to determine whether HBO2 treatment could suppress physical signs of withdrawal in opiate-dependent mice. Male NIH Swiss mice were injected s.c. with morphine sulfate twice a day for 4 days, the daily dose gradually increasing from 50mg/kg on day 1 to 125mg/kg on day 4. On day 5, withdrawal was precipitated by i.p. injection of 5.0mg/kg naloxone. Mice were observed for physical withdrawal signs, including jumping, forepaw tremor, wet-dog shakes, rearing and defecation for 30min. Sixty min prior to the naloxone injection, different groups of mice received either a 30-min or 60-min HBO2 treatment at 3.5atm absolute. HBO2 treatment significantly reduced naloxone-precipitated jumping, forepaw tremor, wet-dog shakes, rearing and defecation. Based on these experimental findings, we concluded that treatment with HBO2 can suppress physical signs of withdrawal syndrome in morphine-dependent mice.