Role of Spinal Cord Endogenous Opioid Peptides in the Antinociceptive Effect of Hyperbaric Oxygen (HBO2)

Abstract

Earlier research demonstrated that HBO2 treatment produces antinociception in an animal model of acute pain (Chung et al., J. Pain 11:847, 2010). We have previously demonstrated that intracerebroventricular (i.c.v.) pretreatment with opioid antagonists can reduce the magnitude of HBO2–induced antinociception in mice. The purpose of this study was to examine the role of opioid mechanisms in the spinal cord in the acute antinociceptive effect of HBO2 in mice. Male NIH Swiss Mice, 18–22 g, were exposed to HBO2 (100% oxygen @ 3.5 ATA) and, after 5 min, responsiveness to HBO2‐induced antinociception was assessed using the acetic acid‐induced abdominal constriction test. Different groups of mice were pretreated by intrathecal (i.t.) injection with the following: normal rabbit serum (NRS); and rabbit antisera (AS) against the rat methionine‐enkephalin (ME), dynorphin1–17 (DYN) and β‐endorphin (βEP). NRS did not produce significant antinociception in control mice. In animals pretreated with NRS (control), HBO2 produced a 59% antinociceptive response. In mice pretreated with DYN AS, ME AS and βEP AS, HBO2 produced 27%, 52% and 46% antinociceptive responses, respectively. In conclusion, the dramatic decrease in the antinociceptive effect in mice pretreated with DYN AS suggests that DYN is the primary endogenous opioid peptide in the spinal cord that mediates HBO2‐induced antinociception. (This research was supported by NIH Grant AT‐007222, the Allen I. White Distinguished Professorship at Washington State University and an institutional Summer Undergraduate Research Fellowship (SURF) Program from ASPET).