Evidence map›Paper›PMID 41143867›Full record

ArticlePain2026

Hydrogen-rich water alleviates neuropathic pain through the modulation of bile acid/Takeda G-protein-coupled receptor 5-mediated autophagy.

Xuejiao Zeng, Jiaqi Lin, Botao Liu, Zehua Su, Yongze Yu, Xin Li, Wenying Duan, Chunzheng Liu, Qianhao Hou, Jinyuan Zhang and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Pain, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Xuejiao ZengDalian Medical University, Dalian, China.
Jiaqi LinDepartment of Pain Management, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Botao LiuDepartment of Pain Medicine, China-Japan Friendship Hospital, Beijing, China.
Zehua SuDepartment of Pain Management, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Yongze YuDepartment of Pain Management, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Xin LiDepartment of Pain Management, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Wenying DuanDepartment of Pain Management, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Chunzheng LiuDepartment of Pain Management, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Qianhao HouDepartment of Pain Management, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Jinyuan ZhangDepartment of Pain Management, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Longqiu YangDepartment of Anesthesiology Management, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Xiaodong LiuDepartment of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Hong Kong SAR, China.
Bifa FanDepartment of Pain Medicine, China-Japan Friendship Hospital, Beijing, China.
Lijun LiaoDepartment of Pain Management, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.ORCID 0000-0002-3698-5636

Funding

Important Weak Subject Construction Project of Pudong Health and Family Planning Commission of Shanghai PWZbr2025-04New Quality Clinical Specialty Program of High-end Medical Disciplinary Construction in Shanghai Pudong New Area 2024-PWXZ-02Pudong New Area Health System Leading Talent Training Program PWR12024-07Shanghai East Hospital Talent Research Launch Plan DFRC2024002Shanghai's 2023"Technology Innovation Action Plan" medical innovation research project 23Y11908300The Healthcare Talents Elite Program of Shanghai Pudong New Area 2025PDWSYCBJ-0
6 · The paper itself

Abstract

abstractNeuropathic pain is a chronic, intractable condition characterized by a complex pathogenesis. Hydrogen-rich water (HRW) has been reported to have possible analgesic properties, but the underlying mechanisms remain unclear. To investigate the effects of HRW, we utilized an L4 spinal nerve ligation (SNL) model in both male and female mice. Pain behaviors were quantitatively assessed using paw withdrawal threshold, paw withdrawal latency, and acetone response tests. Fecal microbiota composition was analyzed through 16S rRNA sequencing, and serum bile acids were assessed by liquid chromatography-mass spectrometry. The expression of bile acid membrane receptor Takeda G-protein-coupled receptor 5 (TGR5) and autophagy markers were evaluated in spinal cord, dorsal root ganglia, and colon through biochemistry experiments. Autophagic structures were examined using transmission electron microscopy. We further validated the roles of TGR5 and autophagy in neuropathic pain through experiments using rapamycin treatment and TGR5 knockout mouse models. The effect of HRW on intestinal barrier function was also tested. We found that HRW effectively ameliorated behavioral deficits associated with SNL-induced neuropathic pain. In addition, HRW facilitated the repair of the damaged gut barrier, restored the disrupted intestinal microbiota, and modulated bile acid metabolism in SNL mice. Interventions with hyodeoxycholic acid and deoxycholic acid produced analgesic effects similar to those of HRW. Takeda G-protein-coupled receptor 5 knockdown reversed the therapeutic effects of HRW and rapamycin. Mechanistically, HRW alleviates neuropathic pain by modulating bile acid metabolites linked to intestinal microbiota and directly or indirectly activating TGR5 in the spinal cord, dorsal root ganglia, and colon, thereby promoting autophagy.

Indexed as

AutophagyBile Acids and SaltsHydrogenNeuralgiaReceptors, G-Protein-CoupledWaterAnimalsDisease Models, AnimalFemaleGastrointestinal MicrobiomeMaleMiceMice, Inbred C57BLMice, KnockoutSpinal CordBile Acids and SaltsGpbar1 protein, mouseHydrogenReceptors, G-Protein-CoupledWaterAutophagyBile acidsHydrogen-rich waterIntestinal floraNeuropathic painTGR5

Identifiers

PMID41143867
PMCPMC12890191

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.