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.

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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.

—Approximately 70 per cent of the total AChE of bovine brain tissue was solubilized by repeated homogenization and centrifugation in 0.32 m sucrose containing EDTA. After ammonium sulphate fractionation, application of the enzyme preparation to an agarose affinity gel column effected a 700‐fold purification. Subsequent molecular filtration separated three active forms of AChE with molecular weights of 130,000, 270,000 and 390,000 with an average specific activity of 575 mmol of acetylthiocholine hydrolysed/mg of protein/h. The complete procedure represented an approximate 23,000‐fold purification of the enzyme from that in the original tissue homogenate. The three forms of AChE exhibited certain differences in properties, including apparent Km values, pH optima and sensitivity to inhibitory agents. Ancillary studies on less purified enzyme preparations by use of polyacrylamide gel electrophoresis and isoelectric focusing techniques also suggested that brain AChE exists in multiple forms.

Earlier research has demonstrated that hyperbaric oxygen (HBO2) can produce an antinociceptive effect in models of acute pain. Recent studies have revealed that HBO2 can produce pain relief in animal models of chronic pain as well. The purpose of the present investigation was to ascertain whether HBO2 treatment might suppress allodynia in rats with neuropathic pain and whether this effect might be blocked by the opioid antagonist naltrexone (NTX). Male Sprague Dawley rats were subjected to a sciatic nerve crush under anesthesia and mechanical thresholds were assessed using an electronic von Frey anesthesiometer. The time course of the HBO2-induced anti-allodynic effect in different treatment groups was plotted, and the area-under-the-curve (AUC) was determined for each group. Seven days after the nerve crush procedure, rats were treated with HBO2 at 3.5 atmospheres absolute (ATA) for 60 min and exhibited an anti-allodynic effect, compared to nerve crush-only control rats. Twenty-four hours before HBO2 treatment, another group of rats was implanted with Alzet® osmotic minipumps that continuously released NTX into the lateral cerebral ventricle for 7 days. These NTX-infused, HBO2-treated rats exhibited an allodynic response comparable to that exhibited by rats receiving nerve crush only. Analysis of the AUC data showed that HBO2 significantly reduced the nerve crush-induced allodynia; this anti-allodynic effect of HBO2 was reversed by NTX. These results implicate opioid receptors in the pain relief induced by HBO2.