Evaluation of hyperbaric oxygen (HBO 2 ) as a treatment for hyperalgesia associated with naloxone‐precipitated withdrawal in morphine‐dependent mice

Opioid dependence has become a major problem in the United States. Withdrawal from opioid drugs is associated with hyperalgesia (increased sensitivity to a pain stimulus) which may contribute to relapse [Carcoba et al., J Addict Dis 30(3): 258–70, 2012]. Hyperbaric oxygen (HBO 2 ) is 100% oxygen at higher than atmospheric pressure. HBO 2 has recently been shown to be effective at decreasing physical signs of withdrawal in morphine‐dependent mice, and there is a growing body of research showing that HBO 2 is effective at decreasing pain in clinical conditions and in preclinical modeling [Nicoara et al., Brain Res. 1648:434–7 , 2016; Efrati et al., PLOS One 10(5)1–25, 2015; Gibbons at al., Brain Res. 1537:111–6, 2013]. The effectiveness of HBO 2 to decrease hyperalgesia caused by opioid withdrawal in an animal model of drug dependence was evaluated in this study. Male and female NIH Swiss mice were made dependent upon morphine by injecting animals s.c. with twice‐daily escalating doses of morphine for 4 consecutive days. On the 5 th day, animals were given a final injection of the highest dose of morphine and injected i.p . with 1.0 mg/kg naloxone 8 hours after the final morphine injection. Animals were treated with 30 min of HBO 2 at 3.5 atmospheres absolute or room air 60 min prior to naloxone injection. Nociception was evaluated using the tail withdrawal, hot plate and paw pressure tests every 10 min for 30 min after naloxone injection. Baseline levels of nociception for each endpoint were taken prior to induction of morphine dependence. Male and female animals exhibited hyperalgesia in the hot plate and paw pressure tests but not the tail withdrawal test. HBO 2 significantly decreased the amount of hyperalgesia in the hot plate and paw pressure tests in male animals. In female animals, HBO 2 had no effect on hyperalgesia in the hot plate test but significantly decreased the level of hyperalgesia associated with the paw pressure test. While no hyperalgesia was seen in the tail withdrawal test, HBO 2 did produce significant antinociception in male and female animals. These intriguing results show that HBO 2 is capable of reducing hyperalgesia associated with opioid withdrawal and warrant further investigation. Furthermore, these results help support previous findings showing that HBO 2 may be effective at decreasing symptoms of opioid withdrawal. Support or Funding Information This research was supported by the Marchionne 12‐month Fellowship from the Department of Psychology at Washington State University, NIH Grant AT‐007222, and the Honors College Distinguished Professorship from Washington State University. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .