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 50 mg/kg on day 1 to 125 mg/kg on day 4. On day 5, withdrawal was precipitated by i.p. injection of 5.0 mg/kg naloxone. Mice were observed for physical withdrawal signs, including jumping, forepaw tremor, wet-dog shakes, rearing and defecation for 30 min. Sixty min prior to the naloxone injection, different groups of mice received either a 30-min or 60-min HBO2 treatment at 3.5 atmospheres 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.

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HBO2 therapy has been approved by the Food and Drug Administration for limited clinical conditions (Gesell, The Hyperbaric Oxygen Therapy Committee Report: Indications and Results, 12th Ed, 2008). It has been reported that HBO2 treatments reduce opioid withdrawal in human subjects (Epifanova, Anesteziol Reanimatol, May‐June 1995 issue, 34‐39). However, no further research has been conducted to investigate the mechanism of HBO2 in reducing opioid withdrawal. The purpose of this research was to determine whether HBO2 treatment could suppress signs of withdrawal in opioid‐dependent mice. Male NIH Swiss mice received repeated s.c. injections of morphine sulfate or saline twice a day for 4 days. The daily dose of morphine sulfate was increased progressively from 50 mg/kg on day 1 to 125 mg/kg on day 4. On day 5, opioid withdrawal was precipitated by intraperitoneal injection of 5.0 mg/kg naloxone. Withdrawal signs in mice, including jumping, forepaw tremor and wet dog shakes, were recorded for 30 min and scored. Sixty min prior to the naloxone injection, different groups of mice received a 30‐min or 60‐min HBO2 treatment at 3.5 atmospheres absolute. The results show that HBO2 treatment caused a dose‐dependent reduction in withdrawal jumping, forepaw tremor and wet dog shakes in opioid‐dependent mice. Grant Funding Source: Supported by NIH Grant AT‐007222 and the Allen I. White Distinguished Professorship.

HBO2 treatment can relieve chronic pain (Thompson et al., Neurosci Res 66:279, 2010). Previously, we reported that HBO2 suppressed PAC‐induced mechanical allodynia (Zhang et al., FASEB J 26:662.9, 2012). The aim of this study was to determine whether HBO2 treatment could also reduce PAC‐induced cold allodynia. Male Sprague Dawley rats, 250‐350 g, were injected intraperitoneally with either 1.0 mg/kg PAC or vehicle on days 0, 2, 4 and 6. On day 7, rats were treated with 60‐min HBO2 at 3.5 atmospheres absolute (ATA) or room air for either one or four days. Cold allodynia was assessed every other day by applying 50 µL acetone to each hind paw. Allodynia was scored using a 0‐3 point scale. Results showed that PAC‐treated rats developed cold allodynia in response to acetone. A single 60‐min HBO2 treatment at 3.5 ATA did not produce obvious recovery from allodynia. However, allodynia was suppressed in rats that underwent four daily 60‐min HBO2 treatments. These results indicate that, while one HBO2 treatment is not sufficient to reduce PAC‐induced cold allodynia, repeated (4×) HBO2 treatment can suppress the development of PAC‐induced cold allodynia. Grant Funding Source: Supported by NIH Grant AT‐007222 and the Allen I. White Distinguished Professorship.