Drinking Hydrogen-Rich Water Alleviates Chemotherapy-Induced Neuropathic Pain Through The Regulation Of Gut Microbiota

Introduction: Chemotherapy-induced neuropathic pain (CINP) is one of the most common complications of chemotherapeutic drugs which limits the dose and duration of potentially life-saving anticancer treatment and compromises the quality of life of patients. Our previous studies have reported that molecular hydrogen (H-2) can be used to prevent and treat various diseases. But the underlying mechanism remains unclear. The aim of the present study was to explore the effects of hydrogen-rich water on gut microbiota in CINP.Methods: All C57BL/6J mice were divided into 4 groups: The group fed with normal drinking water and injected with saline (H2O + Saline), the group fed with normal drinking water and injected with oxaliplatin (H2O + OXA), the group fed with hydrogen-rich water and injected with saline (HW + Saline), and the group fed with hydrogen-rich water and injected with oxaliplatin (HW + OXA). The mechanical paw withdrawal threshold of the mice was tested on days 0, 5, 10, 15 and 20 after hydrogen-rich water treatment. On day 20, feces of mice from different groups were collected for microbial community diversity and structure analysis. The levels of inflammatory cytokines (TNF-alpha and IL-6), oxidative stress factors (OH- and ONOO-), lipopolysaccharide (LPS) and Toll-like receptor 4 (TLR4) were detected in dorsal root ganglia (DRG), L4-6 spinal cord segments and serum by enzyme-linked immunosorbent assay. The expression of TLR4 in DRG and spinal cords was determined by Western blot.Results: The results illustrated that hydrogen-rich water could alleviate oxaliplatin-induced hyperalgesia, reduce the microbial diversity and alter the structure of gut microbiota, reverse the imbalance of inflammatory cytokines and oxidative stress, and decrease the expression of LPS and TLR4.Conclusion: Hydrogen-rich water may alleviate CINP by affecting the diversity and structure of the gut microbiota, and then the LPS-TLR4 pathway, which provides a direction for further research.