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

水素水による胆汁酸/TGR5介在性オートファジー調節を介した神経障害性疼痛の軽減

animal study hydrogen-rich water positive

Abstract

Using a spinal nerve ligation (SNL) mouse model in both sexes, this study examined how hydrogen-rich water (HRW) affects neuropathic pain. Behavioral assessments included paw withdrawal threshold, paw withdrawal latency, and acetone response tests. HRW administration improved pain-related behaviors and was associated with restoration of intestinal barrier integrity, normalization of gut microbiota composition (assessed by 16S rRNA sequencing), and alterations in serum bile acid profiles (measured by LC-MS). Hyodeoxycholic acid and deoxycholic acid each produced analgesic effects comparable to HRW. Expression of the bile acid membrane receptor TGR5 and autophagy markers was evaluated in the spinal cord, dorsal root ganglia, and colon. TGR5 knockout and rapamycin experiments confirmed that both TGR5 signaling and autophagy induction are required for the pain-relieving effects of HRW. The findings indicate that HRW modulates gut microbiota-linked bile acid metabolites and activates TGR5 in neural and intestinal tissues, thereby promoting autophagy and reducing neuropathic pain.

Mechanism

HRW modulates gut microbiota-associated bile acid metabolism, activating the TGR5 receptor in the spinal cord, dorsal root ganglia, and colon, which in turn promotes autophagy and attenuates neuropathic pain signaling.

Bibliographic

Authors
Zeng X, Lin JG, Liu B, Su Z, Yu Y, Li XM, et al.
Journal
Pain
Year
2026 (2026-03-01)
PMID
41143867
DOI
10.1097/j.pain.0000000000003830
PMC
PMC12890191

Tags

Disease:腸管障害 Delivery:水素水経口投与 Mechanism:オートファジー 免疫調節 炎症抑制 酸化ストレス 活性酸素種

Delivery context

Hydrogen-rich water is a low-risk delivery route, but the achievable systemic hydrogen dose is bounded. For clinical applications, inhalation is the most efficient route; inhalation, however, carries explosion risk, and concentration matters (empirical LFL of 10% applies to inhalation environments; high-concentration devices are documented in the Consumer Affairs Agency accident database and are not recommended).

Safety notes

Hydrogen-rich water is a low-risk delivery route, but the achievable systemic hydrogen dose is bounded. For clinical applications, inhalation is the most efficient route; inhalation, however, carries explosion risk, and concentration matters (empirical LFL of 10% applies to inhalation environments; high-concentration devices are documented in the Consumer Affairs Agency accident database and are not recommended).

See also:

Other papers on the same disease / condition

Cite as: H2 Papers — PMID 41143867. https://h2-papers.org/en/papers/41143867
Source: PubMed PMID 41143867