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

Abstract

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.

Reduced antinociceptive responsiveness to hyperbaric oxygen in opioid‐tolerant mice

“…In a rat model of neuropathic pain induced by sciatic nerve crush, we demonstrated that i.c.v. infusion of naltrexone during HBO2 exposure abolished the antiallodynic effect produced by HBO2 (Gibbons et al, 2013). These results support the hypothesis that a central opioid modulating system is responsible for the relief of pain caused by HBO2.…”

Involvement of spinal cord opioid mechanisms in the acute antinociceptive effect of hyperbaric oxygen in mice

“…More recent studies in our laboratory has also demonstrated that HBO 2 treatment can provide pain relief in rats with peripheral nerve injury due to sciatic nerve crush (Gibbons et al, 2012; Gibbons et al, in press) and injections of paclitaxel (Zhang et al, 2012, 2013). These studies were the first to propose that HBO 2 activates a nitric oxide-initiated, opioid-mediated pain-modulating system in the central nervous system.…”

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.…”