Hydrogen-rich water alleviates neuropathic pain through the modulation of bile acid/Takeda G-protein-coupled receptor 5-mediated autophagy
Zeng X et al. · Pain. 2026;167(3):663–677.
Study at a glance
Preclinical
Male and female mice with L4 spinal nerve ligation; additional TGR5 knockout and mechanistic groups
Hydrogen-rich water administered by gavage after spinal nerve ligation · Dose-response experiments identified 3 ppm dissolved H₂ as the concentration used for subsequent experiments.
The full study used scheduled behavioral and tissue assessments after nerve ligation; one single duration does not describe all experiments
The article reports dose-related improvement in pain behaviors, partial restoration of gut-barrier and microbiota measures, and loss or reduction of several effects in TGR5-manipulated experiments.
Complex preclinical study with many experimental comparisons, microbiome and pathway analyses, group sizes commonly n=6 and no human participants. Fecal-transplant experiments and TGR5 overexpression were not performed; sex differences were not resolved.
What kind of evidence is this?
Preclinical
Controlled mouse spinal-nerve-ligation experiments with dose response and mechanistic knockout studies
Musculoskeletal and pain research
H₂-rich water
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
Male and female mice with L4 spinal nerve ligation; additional TGR5 knockout and mechanistic groups
Principal behavioral and tissue comparisons report n=6 per group; the total number across all experiments was not stated as one figure
The full study used scheduled behavioral and tissue assessments after nerve ligation; one single duration does not describe all experiments
Hydrogen-rich water administered by gavage after spinal nerve ligation
H₂ dissolved in water — H₂ only, not Brown’s gas.
Dose-response experiments identified 3 ppm dissolved H₂ as the concentration used for subsequent experiments.
Sham-operated and spinal-nerve-ligation mice receiving double-distilled water; additional mechanistic comparator groups
Outcomes and reported result
Mechanical, heat and cold pain behaviors; spinal and dorsal-root microglia; gut barrier and microbiota; bile acids; TGR5 and autophagy markers
The article reports dose-related improvement in pain behaviors, partial restoration of gut-barrier and microbiota measures, and loss or reduction of several effects in TGR5-manipulated experiments.
Dose, principal methods, results, supplemental links, conflicts and limitations checked in the open-access full text; the many experimental groups have not yet been extracted outcome by outcome.
A reported association, difference or mechanism is not automatically a clinical benefit.
Limitations and applicability
Complex preclinical study with many experimental comparisons, microbiome and pathway analyses, group sizes commonly n=6 and no human participants. Fecal-transplant experiments and TGR5 overexpression were not performed; sex differences were not resolved.
Male and female mouse models of nerve-ligation neuropathic pain, not people with chronic pain.
No single-study GRADE certainty rating is assigned. Read how records and evidence assessments are prepared.
Sources and record status
PMID: 41143867 · DOI: 10.1097/j.pain.0000000000003830
Open-access full text is available through PMC.
Open-access PMC full text and PubMed bibliographic record.
10 August 2026
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