Reduced antinociceptive responsiveness to hyperbaric oxygen in opioid-tolerant mice

Eur J Pain. 2014 Aug;18(7):1032-9. doi: 10.1002/j.1532-2149.2013.00448.x. Epub 2014 Jan 6.


Background: Hyperbaric oxygen (HBO2 ) therapy can produce analgesia in patients experiencing various conditions of chronic pain. Previously, we reported that naloxone antagonized the acute antinociceptive effect of both brief (11 min) and longer (60 min) HBO2 treatments. This implied a possible role for opioid receptors in the antinociceptive effects of HBO2 .

Objectives: The aim of this study was to determine whether mice previously rendered as tolerant to opioid agonists would exhibit a reduced antinociceptive responsiveness to HBO2 .

Methods: Male NIH Swiss mice were given repeated injections of the opioid agonists morphine, fentanyl or (-)-U50488H over 4 days to induce tolerance at their respective opioid receptors. Mice receiving saline according to a similar injection schedule served as a vehicle control group. On day 5, 15 h after the last injection, mice received either an antinociceptive challenge dose of the opioid agonists or a 30-min HBO2 exposure at 3.5 atmosphere absolute. The antinociception was then assessed by the 0.6% acetic acid-induced abdominal constriction test.

Results: The results showed that mice rendered as tolerant to morphine, fentanyl or (-)-U50488H pretreatment all exhibited reduced antinociceptive responsiveness to themselves and HBO2 .

Conclusions: These results demonstrated that both μ- and κ-opioid receptors are involved in mediation of the acute antinociceptive response to HBO2 .

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesia / methods
  • Analgesics / therapeutic use*
  • Analgesics, Opioid / therapeutic use*
  • Animals
  • Hyperbaric Oxygenation*
  • Mice
  • Pain Management
  • Pain* / metabolism
  • Pain* / physiopathology
  • Receptors, Opioid, kappa / metabolism
  • Receptors, Opioid, mu / metabolism


  • Analgesics
  • Analgesics, Opioid
  • Receptors, Opioid, kappa
  • Receptors, Opioid, mu