Hydrogen Water Reduces Chronic Pain After Bone Fractures in Mice
- Authors
- Yanting Wang, Pei Wang, Cuicui Liu, Wei Chen, Pingping Wang, Lili Jiang
- Journal
- Brain Sciences
- Year
- 2022
- DOI
- 10.3390/brainsci12121610
- Study Type
- Mouse
- Outcome
- Positive
- Peer Reviewed
- Yes
- Country
- China
- Health Condition
- Chronic Pain
- Body System
- Nervous System
TL;DR
Hydrogen-rich saline may help reduce chronic pain and iron buildup in the spine after a bone fracture by targeting specific inflammation-related molecules.
Key Finding
Hydrogen-rich saline reduced chronic pain after bone fractures in mice by suppressing inflammatory molecules (CXCL1/CXCR2) and preventing iron accumulation in the spinal cord.
Summary
Researchers used mice with bone fractures to test whether hydrogen-rich saline (a salt solution containing dissolved hydrogen gas) could reduce chronic pain that develops after fractures. They found that injections of hydrogen-rich saline reduced pain sensitivity and lowered levels of inflammatory molecules and iron buildup in the spinal cord, suggesting hydrogen may work by reducing inflammation and preventing harmful iron accumulation in nerve tissue.
Practical Takeaway
This is early-stage research in mice only, so it cannot yet be applied to humans. The study suggests hydrogen-rich saline may have potential for managing post-fracture pain through anti-inflammatory mechanisms, but human clinical trials would be needed to determine if these results translate to people and whether this approach is safe and effective.
Abstract
Purpose: Neuroinflammation often initiates iron overload in the pathogenesis of neurological disorders. Chemokine-driven neuroinflammation is required for central sensitization and chronic allodynia following fractures, but specific molecular modulations are elusive. This present study explored whether hydrogen-rich saline, as one potent anti-inflammatory pharmaceutical, could alleviate fracture-caused allodynia by suppressing chemokine CXCL1 expression and iron overload. Methods: A mouse model of tibial fracture with intramedullary pinning was employed for establishing chronic allodynia. Three applications of hydrogen-rich saline (1, 5 or 10 mL/kg) were administrated intraperitoneally on a daily basis from days 4 to 6 following fractures. Spinal CXCL1 and its receptor CXCR2 levels, transferrin receptor 1 (TfR1) expression and iron concentration were examined. Recombinant CXCL1, a selective CXCR2 antagonist and an iron chelator were used for verification of mechanisms. Results: Repetitive injections of hydrogen-rich saline (5 and 10 mL/kg but not 1 mL/kg) prevent fracture-caused mechanical allodynia and cold allodynia in a dose-dependent manner. Single exposure to hydrogen-rich saline (10 mL/kg) on day 14 after orthopedic surgeries controls the established persistent fracture allodynia. Furthermore, hydrogen-rich saline therapy reduces spinal CXCL1/CXCR2 over-expression and TfR1-mediated iron accumulation in fracture mice. Spinal CXCR2 antagonism impairs allodynia and iron overload following fracture surgery. Intrathecal delivery of recombinant CXCL1 induces acute allodynia and spinal iron overload, which is reversed by hydrogen-rich saline. Moreover, iron chelation alleviates exogenous CXCL1-induced acute pain behaviors. Conclusions: These findings identify that hydrogen-rich saline confers protection against fracture-caused chronic allodynia via spinal down-modulation of CXCL1-dependent TfR1-mediated iron accumulation in mice.