Hydrogen Water Reduces Fibromyalgia Pain and Depression in Mice
- Authors
- Sylmara Esther Negrini-Ferrari, Ignacio Martínez-Martel, Olga Pol
- Journal
- International Journal of Molecular Sciences
- Year
- 2026
- DOI
- 10.3390/ijms27073051
- Study Type
- Mouse
- Outcome
- Positive
- Peer Reviewed
- Yes
- Country
- Spain
- Health Condition
- Fibromyalgia
- Body System
- Nervous System
TL;DR
Hydrogen-rich water reduced fibromyalgia-like pain sensitivity and depressive-like behaviors in male and female mice, with effects linked to reduced spinal oxidative stress, altered ERK signaling, and normalization of amygdala inflammatory and antioxidant markers.
Key Finding
Hydrogen-rich water reversed fibromyalgia-like pain and depressive behaviors in mice, with greater effectiveness in females, by reducing oxidative stress in the spinal cord and brain regions involved in pain and mood.
Summary
This study tested whether hydrogen-rich water could help treat fibromyalgia-like pain and depression in mice. Researchers gave mice a drug to create fibromyalgia symptoms, then treated some with hydrogen-rich water while measuring pain sensitivity and mood-related behaviors. Hydrogen-rich water reduced pain responses and reversed depression-like behaviors in both male and female mice, though females showed greater improvement. The researchers found that hydrogen worked by reducing harmful molecules called free radicals in specific brain regions.
Practical Takeaway
While this mouse study suggests hydrogen-rich water may have potential for fibromyalgia and related mood symptoms, it is early-stage research that has not been tested in humans. The sex-dependent differences observed in mice may or may not apply to people. Anyone with fibromyalgia or depression should consult their healthcare provider before considering hydrogen water as a treatment.
Abstract
Fibromyalgia is a chronic nociplastic pain condition frequently accompanied by affective disturbances, particularly depression, for which effective treatments remain limited. Increasing evidence implicates central oxidative stress, maladaptive synaptic plasticity, and neuroinflammatory alterations in its pathophysiology. This study investigated the therapeutic effects of molecular hydrogen (H2) in a reserpine-induced murine model of fibromyalgia, with emphasis on sex-dependent and region-specific mechanisms. Male and female C57BL/6 mice received repeated reserpine injections to induce fibromyalgia-like symptoms. Mechanical allodynia, thermal hyperalgesia, cold allodynia, and depressive-like behaviors were assessed, followed by molecular analyses in the spinal cord and amygdala. Reserpine induced persistent nociceptive hypersensitivity and depressive-like behaviors in both sexes, with earlier cold allodynia in females. Hydrogen-rich water (HRW) progressively reversed mechanical and thermal hypersensitivity and rapidly abolished cold allodynia, showing greater efficacy in females. HRW also normalized depressive-like behaviors in both sexes. At the molecular level, HRW reduced spinal oxidative stress and ERK-dependent plasticity without altering spinal NLRP3 expression, whereas it fully reversed NLRP3 upregulation and HO-1 downregulation in the amygdala. HRW additionally engaged sex-dependent antioxidant pathways in the spinal cord. These findings indicate that H2 alleviates sensory and affective alterations through region- and sex-dependent central mechanisms, supporting HRW as a promising therapeutic strategy for nociplastic pain and its affective comorbidities.