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

Abstract

Chronic inflammatory pain is manifested in many diseases. The potential use of molecular hydrogen (H2) as a new therapy for neurological disorders has been demonstrated. Recent studies prove its analgesic properties in animals with neuropathic pain, but the possible antinociceptive, antidepressant, and/or anxiolytic actions of H2 during persistent inflammatory pain have not been investigated. Therefore, using male mice with chronic inflammatory pain incited by the subplantar injection of complete Freud’s adjuvant (CFA), we assessed the actions of hydrogen-rich water (HRW) systemically administered on: (1) the nociceptive responses and affective disorders associated and (2) the oxidative (4-hydroxy-2-nonenal; 4-HNE), inflammatory (phosphorylated-NF-kB inhibitor alpha; p-IKBα), and apoptotic (Bcl-2-like protein 4; BAX) changes provoked by CFA in the paws and amygdala. The role of the antioxidant system in the analgesia induced by HRW systemically and locally administered was also determined. Our results revealed that the intraperitoneal administration of HRW, besides reducing inflammatory pain, also inhibited the depressive- and anxiolytic-like behaviors associated and the over expression of 4-HNE, p-IKBα, and BAX in paws and amygdala. The contribution of the nuclear factor erythroid 2-related factor 2/heme oxygenase 1 and NAD(P)H: quinone oxidoreductase 1 pathway in the analgesic activities of HRW, systemically or locally administered, was also shown. These data revealed the analgesic, antidepressant, and anxiolytic actions of HRW. The protective, anti-inflammatory, and antioxidant qualities of this treatment during inflammatory pain were also demonstrated. Therefore, this study proposes the usage of HRW as a potential therapy for chronic inflammatory pain and linked comorbidities.

Gas therapy strategies for depression and schizophrenia: A review

“…The injection of HRW into the abdominal cavity of male mice with chronic inflammatory pain can not only alleviate the inflammatory pain, but also inhibited the behaviors related to depression-like and anxiety-like behaviors. [71] Repeated inhalation of high concentrations of H 2 gas relieves stress-induced depression and anxiety in mice. [73] Saline enriched with H 2 had similar anxiolytic effects in morphine withdrawal mice.…”

“…Endogenous Inhibition AG Schizophrenia [27] L-NOARG Schizophrenia [26] AG Depression [24] 7-NI Depression [22] Stimulation Heme-lysinate Depression [32] External External stimuliresponsive gasotransmitter prodrugs SNP Depression [34] SNP Schizophrenia [35] Molsidomine Depression [46] Molsidomine Schizophrenia [47] DETA/NONOate Depression [52] CORM-2 Depression [53] CORM-3 Depression [55] CO-rich saline or CO gas Depression [56] NaHS Depression [58] Na 2 S Depression [64] DADS Depression [67] Hydrogen-Rich Water Depression [71] Nano-gas carrier CORM-2-SLN Depression [54] These gas-related drugs can affect the development of depression and schizophrenia by either stimulating the production of gas or inhibiting its production. thus reduces cGMP production.…”

“…The expression of oxidative and inflammatory biomarkers in specific brain areas of depression patients has increased, while H 2 has the ability to reduce inflammation by reducing IL-6, IL-1β, IL-12 and TNF-α. [71,72] Repeated inhalation of H 2 and oxygen mixture [67%: 33% (V/V)] can significantly reduce the depression-like and anxiety-like behavior induced by acute and chronic stress in mice through tail suspension test, forced swimming test, novel inhibition feeding test and open field test. The injection of HRW into the abdominal cavity of male mice with chronic inflammatory pain can not only alleviate the inflammatory pain, but also inhibited the behaviors related to depression-like and anxiety-like behaviors.…”

“…The injection of HRW into the abdominal cavity of male mice with chronic inflammatory pain can not only alleviate the inflammatory pain, but also inhibited the behaviors related to depression-like and anxiety-like behaviors. [71]…”

A Novel Therapy for Cisplatin-Induced Allodynia and Dysfunctional and Emotional Impairments in Male and Female Mice

“…Recent experiments further revealed that the therapeutic administration of hydrogen-rich water (HRW) has beneficial effects in animals with paclitaxel-induced neuropathic pain [37]. This treatment also reduced the nociceptive and emotive disturbances occasioned by nerve injury and persistent paw inflammation in male mice [38,39]. There is also evidence that H 2 exhibits antidepressant and/or anxiolytic properties in animals with traumatic brain injury [40] or chronic stress-induced depressive-and anxiety-like comportments [41] and further improves psychiatric illnesses in humans [42].…”