Treatment with Hydrogen-Rich Water Improves the Nociceptive and Anxio-Depressive-like Behaviors Associated with Chronic Inflammatory Pain in Mice.

Abstract

Using male mice with chronic inflammatory pain induced by subplantar injection of complete Freund's adjuvant (CFA), this study examined the effects of systemically administered hydrogen-rich water (HRW) on nociceptive responses, depressive- and anxiety-like behaviors, and molecular markers of oxidative stress (4-HNE), inflammation (p-IKBα), and apoptosis (BAX) in paw tissue and the amygdala. Intraperitoneal HRW administration reduced pain-related behaviors and suppressed overexpression of all three markers in both tissues. The Nrf2/HO-1 and NQO1 antioxidant pathways were identified as contributors to the analgesic effects observed under both systemic and local HRW delivery conditions. These findings indicate that HRW exerts antinociceptive, antidepressant, and anxiolytic effects alongside anti-inflammatory and antioxidant actions in a persistent inflammatory pain model.

Mechanism

HRW activates the Nrf2/HO-1 and NQO1 antioxidant pathways, thereby suppressing CFA-induced overexpression of 4-HNE, p-IKBα, and BAX in peripheral and central tissues, producing analgesic, anti-inflammatory, and antioxidant effects.