Hyperbaric Oxygen Treatment Induces a 2-Phase Antinociceptive Response of Unusually Long Duration in Mice

Abstract 

Hyperbaric oxygen (HBO₂) therapy is approved by the FDA for limited clinical indications but is reported to produce pain relief in several chronic pain conditions. However, there have been no studies to explain this apparent analgesic effect of HBO₂. Research conducted in our laboratory demonstrates that 4 daily 60-minute HBO₂ treatments at 3.5 absolute atmospheres induced an unparalleled antinociceptive response that consists of 1) an early phase that lasted at least 6 hours after the HBO₂ treatment before dissipating; and 2) a late phase that emerged about 18 hours after the early phase and lasted for up to 3 weeks. The early phase was sensitive to antagonism by acutely intracerebroventricular (i.c.v.)-administered opioid antagonist naltrexone and the nitric oxide synthase (NOS)-inhibitor L-NAME. The late phase was inhibited by treatment with i.c.v. naltrexone or L-NAME during the 4 daily HBO₂ treatments but was not antagonized by either naltrexone or L-NAME following acute pretreatment 2 weeks after HBO₂ treatment. These experimental results implicate a novel mechanism that is activated by HBO₂, resulting in an antinociceptive response of unusually long duration that is of potential interest in the clinical management of pain.

Perspective

Hyperbaric oxygen treatment of mice can induce a 2-phase antinociceptive response of unusually long duration. Nitric oxide and opioid receptors appear to initiate or mediate both phases of the antinociceptive response. Further elucidation of the underlying mechanism may potentially identify molecular targets that cause long-lasting activation of endogenous analgesic systems.

Key words: Hyperbaric oxygen, antinociception, nitric oxide, opioid receptors, mice