Hydrogen Gas Reduces Post-Surgery Pain by Blocking Brain Inflammation
- Authors
- Juan Li, Shirong Ruan, Jinhui Jia, Qian Li, Rumeng Jia, Li Wan, Xing Yang, Peng Teng, Qilin Peng, Ya-Dan Shi, Yu Pan, Yinbing Pan, Man-Lin Duan, Wen-Tao Liu, Li Zhang, Li, Liang Hu
- Journal
- Journal of Neuroinflammation
- Year
- 2023
- DOI
- 10.1186/s12974-022-02670-0
- Study Type
- Mouse
- Outcome
- Positive
- Peer Reviewed
- Yes
- Country
- China
- Health Condition
- Postoperative Pain
- Body System
- Nervous System
TL;DR
Hydrogen gas (H2) may be a potential treatment for reducing postoperative pain by affecting certain molecules and pathways in the body.
Key Finding
Hydrogen gas reduced postoperative pain in mice by activating a protein called Trx1, which suppressed inflammatory signaling pathways in the spinal cord.
Summary
Researchers used mice to test whether hydrogen gas could reduce pain after surgery. They found that surgery increased activity of certain pain-promoting proteins in the spinal cord, and that hydrogen gas reduced these proteins and decreased pain sensitivity. The effect worked by activating a protective protein called Trx1, which then blocked a chain of inflammatory signals that normally amplify pain.
Practical Takeaway
This mouse study suggests hydrogen may have potential for managing postoperative pain through anti-inflammatory mechanisms, but it is early-stage research. Human studies would be needed to determine if these findings apply to people, and the study does not yet indicate what dose or delivery method would be effective in clinical settings.
Abstract
Background: Postoperative pain is a serious clinical problem with a poorly understood mechanism, and lacks effective treatment. Hydrogen (H2) can reduce neuroinflammation; therefore, we hypothesize that H2 may alleviate postoperative pain, and aimed to investigate the underlying mechanism. Methods: Mice were used to establish a postoperative pain model using plantar incision surgery. Mechanical allodynia was measured using the von Frey test. Cell signaling was assayed using gelatin zymography, western blotting, immunohistochemistry, and immunofluorescence staining. Animals or BV-2 cells were received with/without ASK1 and Trx1 inhibitors to investigate the effects of H2 on microglia. Results: Plantar incision surgery increased MMP-9 activity and ASK1 phosphorylation in the spinal cord of mice. MMP-9 knockout and the ASK1 inhibitor, NQDI-1, attenuated postoperative pain. H2 increased the expression of Trx1 in the spinal cord and in BV-2 cells. H2 treatment mimicked NQDI1 in decreasing the phosphorylation of ASK1, p38 and JNK. It also reduced MMP-9 activity, downregulated pro-IL-1β maturation and IBA-1 expression in the spinal cord of mice, and ameliorated postoperative pain. The protective effects of H2 were abolished by the Trx1 inhibitor, PX12. In vitro, in BV-2 cells, H2 also mimicked NQDI1 in inhibiting the phosphorylation of ASK1, p38, and JNK, and also reduced MMP-9 activity and decreased IBA-1 expression induced by LPS. The Trx1 inhibitor, PX12, abolished the protective effects of H2 in BV-2 cells. Conclusions: For the first time, the results of our study confirm that H2 can be used as a therapeutic agent to alleviate postoperative pain through the Trx1/ASK1/MMP9 signaling pathway. MMP-9 and ASK1 may be the target molecules for relieving postoperative pain.