A Prolonged Nitric Oxide-Dependent, Opioid-Mediated Antinociceptive Effect of Hyperbaric Oxygen in Mice

Abstract

Hyperbaric oxygen (HBO 2 ) therapy is reported to cause pain relief in several conditions of chronic pain. A single 60-min session of HBO 2 treatment produced a prolonged antinociceptive effect in mice that persisted for 90 min after cessation of treatment. The HBO 2 -induced antinociception was significantly attenuated by pretreatment prior to HBO 2 exposure with the opioid antagonist naltrexone, the non-specific nitric oxide synthase (NOS)-inhibitor N G -nitro-L-arginine methyl ester (L-NAME) and the selective neuronal NOS-inhibitor S-methyl-L-thiocitrulline (SMTC) but not the selective endothelial NOS-inhibitorThe antinociception was also significantly reduced by central pretreatment with a rabbit antiserum against dynorphin 1-13 but not by rabbit antisera against either β-endorphin or methionine-enkephalin. The prolonged antinociceptive effect at 90 min after HBO 2 -induced treatment was also significantly attenuated by naltrexone but not L-NAME administered 60 min following HBO 2 treatment but prior to nociceptive testing. These findings indicate that the antinociception that persists for 90 min after HBO 2 exposure is mediated by nitric oxide (NO) and opioid mechanisms but that the NO involvement is critical during the HBO 2 treatment and not at the time of nociceptive testing. These results are consistent with the concept that HBO 2 may induce an NO-dependent release of opioid peptide to cause a long-acting antinociceptive effect. Words for IndexingHyperbaric Oxygen; Nitric Oxide; Opioid; Antinociception; Mice Corresponding Author: Dr. Raymond M. Quock, Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, P.O. Box 646534, Pullman,. Perspective This article present evidence of a persistent antinociceptive effect of hyperbaric oxygen treatment that is mediated by opioid and nitric oxide mechanisms. Further elucidation of the underlying mechanism could potentially identify molecular targets to cause a longer-acting activation of endogenous pain-modulating systems.

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

“…We also found that inhibiting either the activity or the expression of nNOS can interfere with the antinociceptive effect of HBO 2 following 11- and 60-min treatments. This suggests that NO initiates a process that culminates in the relief of pain (Ohgami et al, 2009; Zelinski et al, 2009) in the experimental pain model used.…”

“…This nociceptive model was selected over tests employing a thermal noxious stimulus because this paradigm is significantly more sensitive to detection of κ opioid antinociceptive activity than are thermal tests (Tyers, 1980) and because our previous studies have implicated κ opioid mechanisms in mediation of HBO 2 -induced antinociception (Zelinski et al, 2009). …”

“…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).…”

Hyperbaric oxygen treatment suppresses withdrawal signs in morphine-dependent mice

“…One reason for selection of 5.0 mg/kg of naloxone as our dose for precipitating withdrawal was a previous finding from our laboratory that HBO 2 -induced antinociception in rodents was sensitive to antagonism by both opioid antagonist drugs as well as rabbit antisera against selected endogenous opioid peptides, namely dynorphin [Zelinski et al ., 2009; Heeman et al ., 2013; Gibbons et al ., 2013]. This suggests that a mechanism of HBO 2 -induced antinociception is stimulation of neuronal release of opioid peptides.…”

“…Previously, we reported that HBO 2 produced an antinociceptive effect in mice that was dependent on both nitric oxide (NO) and opioid receptors [Zelinski et al ., 2009]. Further studies suggested that HBO 2 might be capable of stimulating neuronal release of endogenous opioid peptides [Heeman et al ., 2013].…”