Hyperbaric oxygen (HBO) therapy is reported to attenuate pain in both clinical pain conditions and animal pain models, but
the underlying mechanism remains to be investigated. Here, we show that 7 daily 60-minute HBO (100% oxygen, 2 atmosphere absolute)
treatments effectively and persistently inhibited heat hyperalgesia, mechanical allodynia, and paw edema induced by peripheral
injection of complete Freund's adjuvant (CFA). Five daily 60-minute HBO treatments also produced a prolonged reversal effect
of the ongoing inflammatory pain. Furthermore, such an HBO treatment reduced CFA-induced activation of glial cells, phosphorylation
of mitogen-activated protein kinases, and production of a variety of proinflammatory cytokines (tumor necrosis factor alpha
[TNF-α], interleukin-1 beta [IL-1β], and interleukin-6 [IL-6]) and chemokines (monocyte chemoattractant protein-1 [MCP-1],
keratinocyte-derived chemokine [KC], and IFN-gamma-inducible protein 10 [IP-10]) in the spinal cord. HBO treatment also decreased
lipopolysaccharide-induced mRNA expression of these cytokines and chemokines in primary cultures of astrocytes and microglia.
In addition, the mRNA expressions of IL-1β, IL-6, MCP-1, KC, and IP-10 in the inflamed paw skin were decreased by HBO. Taken
together, these data suggest that HBO treatment is an effective therapy for inflammatory pain in animals. The inhibition of
the neuroinflammation that is mediated by glial cells and inflammatory mediators may, at least in part, contribute to the
antinociceptive effect of HBO therapy. PERSPECTIVE: Our results suggest that repetitive HBO treatment attenuates CFA-induced
pain and reduces glial activation and inflammatory mediators' production. These findings provide the evidence of the antinociception
effect of HBO on inflammatory pain and characterize some of the underlying mechanisms.