Molecular Hydrogen Reverses Nociplastic Pain and Depressive-like Behaviors via Region- and Sex-Dependent Central Mechanisms
Negrini-Ferrari SE et al. · Int J Mol Sci. 2026;27(7):3051.
What kind of evidence is this?
Preclinical
Controlled male and female mouse experiment with behavioral and regional molecular analyses
Musculoskeletal and pain research
H₂-rich water
Not reported in this record.
Not reported in this record.
Methods at a glance
Male and female C57BL/6 mice with reserpine-induced fibromyalgia-like features
Behavioral comparisons n=6/group; molecular analyses n=4/group
Six consecutive treatment days, with tissue collection on day 28 after reserpine exposure
Hydrogen-rich water for six consecutive days
H₂ dissolved in water — H₂ only, not Brown’s gas and not inhalation.
Numeric H₂ concentration was not identified in the extracted full-text passages.
Not applicable — oral water, not gas inhalation.
No O₂ was co-delivered as part of the intervention.
Reserpine and vehicle mice receiving vehicle water
Outcomes and reported result
Mechanical, thermal and cold sensitivity, depressive-like behaviors, oxidative stress, ERK, NLRP3 and antioxidant proteins in spinal cord and amygdala
The article reports improvement in pain-like and depressive-like behaviors, with region- and sex-dependent molecular changes. Spinal NLRP3 was not altered by H₂ water.
Behavioral and molecular results checked in the open-access full text; numeric water concentration still requires confirmation.
A reported association, difference or mechanism is not automatically a clinical benefit. Null findings, outcome type, study design and precision all matter.
Cautions and applicability
Mouse model with small groups, multiple behavioral and molecular outcomes and sex-stratified analyses. It does not establish benefit in people with fibromyalgia or depression.
Reserpine-induced nociplastic-pain-like behavior in mice, not human fibromyalgia.
Not reported in this record.
Not reported in this record.
Not reported in this record.
No single-study GRADE certainty rating is assigned. Certainty is assessed by important outcome across a complete eligible evidence set, not by attaching a final grade to one source.
Sources and record status
PMID: 41977237 · DOI: 10.3390/ijms27073051
Open-access full text is available through PMC.
Open-access PMC full text and PubMed record.
2026-08-10