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

Abstract

Hyperbaric oxygen (HBO 2 ) 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 HBO 2 . Research conducted in our laboratory demonstrates that four daily 60-min HBO 2 treatments at 3.5 ATA induced an unparalleled antinociceptive response that consists of 1) an early phase that lasted at least six hours after the HBO 2 treatment before dissipating; and 2) a late phase that emerged about 18 hours after the early phase and lasted for up to three 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 four HBO 2 treatments but was not antagonized by either naltrexone or L-NAME following acute pretreatment two weeks after HBO 2 treatment. These experimental results implicate a novel mechanism that is activated by HBO 2 , 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 two-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.

Hyperbaric oxygen treatment suppresses withdrawal signs in morphine-dependent mice

“…Our own studies have consistently demonstrated that inhibition of brain NOS antagonizes HBO 2 -induced antinociception [Ohgami et al , 2009; Zelinski et al , 2009; Chung et al , 2010]. These findings suggest that HBO 2 increases NOS activity.…”

Involvement of brain opioid receptors in the anti-allodynic effect of hyperbaric oxygen in rats with sciatic nerve crush-induced neuropathic pain

“…Mice that received four daily 60-min HBO 2 treatments exhibited an unusually long-lasting biphasic antinociceptive effect (Chung et al, 2010). There was an early-phase antinociceptive response that lasted approximately 6 h before dissipating by 12 h. However, a late-phase antinociceptive response reemerged at 24 h and peaked five days after the last HBO 2 treatment which lasted for up to three weeks.…”

“…Research from our laboratory demonstrated that HBO 2 treatment effectively reduces pain in animal models of acute pain (Ohgami et al, 2009; Zelinski et al, 2009a; Chung et al, 2010; Quock et al, 2011). Our results from these experiments show that HBO 2 -induced antinociception is significantly attenuated by the opioid antagonist naltrexone (NTX).…”

The acute antinociceptive effect of HBO2 is mediated by a NO–cyclic GMP–PKG–KATP channel pathway in mice

“…Previously we implicated the biological regulator nitric oxide (NO) in the antinociceptive response of mice to different conditions of hyperbaric oxygen (HBO 2 ) treatment (Ohgami et al, 2009; Zelinski et al, 2009; Chung et al, 2010). The acute antinociceptive response to HBO 2 was significantly reduced by pharmacological inhibition of nitric oxide synthase (NOS) activity or suppression of neuronal NOS (nNOS) expression by an anti-sense oligodeoxynucleotide directed against nNOS (Ohgami et al, 2009).…”