# Hydrogen-Rich Water as a Novel Therapeutic Strategy for the Affective Disorders Linked with Chronic Neuropathic Pain in Mice.
> 水素水が慢性神経障害性疼痛に伴う情動障害に及ぼす影響：マウスを用いた検討


## Abstract

Using a chronic constriction injury (CCI) model of the sciatic nerve in male mice, this study examined how repeated administration of hydrogen-rich water (HRW) affects neuropathic pain and associated mood disturbances. HRW suppressed both allodynia and hyperalgesia induced by CCI, while also reducing anxiety-like and depressive-like behaviors. Mechanistic analyses indicated that antioxidant enzymes—heme oxygenase 1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO1)—along with ATP-sensitive potassium channels, contribute to the analgesic effects of HRW. A positive interaction between the HO-1 enzyme system and molecular hydrogen was identified during neuropathic conditions. In dorsal root ganglia and amygdala tissue from nerve-injured animals, antioxidant, anti-inflammatory, and antiapoptotic effects were also documented.

### Mechanism

HRW activates antioxidant enzymes HO-1 and NQO1 and ATP-sensitive potassium channels, reducing oxidative stress, inflammation, and apoptosis in dorsal root ganglia and amygdala, thereby alleviating neuropathic pain and mood-related deficits.

## Bibliographic

- **Authors**: Martínez-Serrat M, Martínez-Martel I, Coral-Pérez S, Bai X, Batallé G, Pol O
- **Journal**: Antioxidants (Basel)
- **Year**: 2022 (2022-09-16)
- **PMID**: [36139900](https://pubmed.ncbi.nlm.nih.gov/36139900/)
- **DOI**: [10.3390/antiox11091826](https://doi.org/10.3390/antiox11091826)
- **PMC**: [PMC9495356](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9495356/)
- **Study type**: animal study
- **Delivery route**: hydrogen-rich water
- **Effect reported**: positive

## 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:
- [Inhalation concentration and LFL / UFL](https://h2-papers.org/en/safety-notes/inhalation-concentration)
- [Consumer Affairs Agency accident cases](https://h2-papers.org/en/safety-notes/accident-cases)
- [Inhalation safety threshold lineage](https://h2-papers.org/en/safety-notes/lineage)

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> **Cite as**: H2 Papers — PMID 36139900. https://h2-papers.org/en/papers/36139900
> **Source**: PubMed PMID [36139900](https://pubmed.ncbi.nlm.nih.gov/36139900/)