Hydrogen attenuates postoperative pain through Trx1/ASK1/MMP9 signaling pathway
Li J et al. · J Neuroinflammation. 2023;20(1):22.
Study at a glance
Preclinical
Mice with plantar-incision postoperative pain and cultured BV-2 microglial cells
Hydrogen-rich saline 5 mL/kg intraperitoneally twice daily in mice; H₂-rich medium in the cell experiments · 5 mL/kg H₂-rich saline twice daily; numeric dissolved-H₂ concentration was not located in the extracted methods.
Twice-daily treatment with spinal and behavioral assessment at 24 hours and day 5
The article reports less mechanical allodynia, MMP-9 activity, inflammatory signaling and microglial activation with H₂-rich saline; a Trx1 inhibitor abolished several reported effects.
Multiple preclinical cohorts and mechanistic interventions; no human participants and no clinical postoperative-pain endpoint.
What kind of evidence is this?
Preclinical
Controlled mouse plantar-incision experiments with genetic and pharmacologic pathway comparisons plus BV-2 cell experiments
Musculoskeletal and pain research
Other forms
Information not yet classified
Some editorial classification fields are still pending. The source-reported outcomes and result are shown below; Hydrogenology does not infer a positive or negative signal from prose automatically.
Methods
Mice with plantar-incision postoperative pain and cultured BV-2 microglial cells
Behavioral cohorts commonly used n=12 and mechanistic assays n=4–6; several separate cohorts were used
Twice-daily treatment with spinal and behavioral assessment at 24 hours and day 5
Hydrogen-rich saline 5 mL/kg intraperitoneally twice daily in mice; H₂-rich medium in the cell experiments
H₂ dissolved in saline or culture medium — not Brown’s gas and not gas inhalation in the in-vivo treatment.
5 mL/kg H₂-rich saline twice daily; numeric dissolved-H₂ concentration was not located in the extracted methods.
Sham and plantar-incision groups receiving vehicle, plus MMP-9 knockout and ASK1/Trx1 inhibitor comparisons
Outcomes and reported result
Mechanical allodynia, spinal Trx1/ASK1/p38/JNK signaling, MMP-9, cytokines and microglial activation
The article reports less mechanical allodynia, MMP-9 activity, inflammatory signaling and microglial activation with H₂-rich saline; a Trx1 inhibitor abolished several reported effects.
Dose, principal cohorts, mechanistic comparisons, figures, funding and conflicts checked in the open-access full text; numeric dissolved-H₂ concentration remains unconfirmed.
A reported association, difference or mechanism is not automatically a clinical benefit.
Limitations and applicability
Multiple preclinical cohorts and mechanistic interventions; no human participants and no clinical postoperative-pain endpoint.
Experimental plantar-incision pain in mice, not postoperative pain treatment in people.
No single-study GRADE certainty rating is assigned. Read how records and evidence assessments are prepared.
Sources and record status
PMID: 36737785 · DOI: 10.1186/s12974-022-02670-0
Open-access full text is available through PMC and the publisher.
Open-access PMC/publisher full text and PubMed record; no retraction or expression of concern was shown in the checked records on 7 August 2026.
10 August 2026
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