ArticleBrain sciences2022
Hydrogen-Rich Saline Attenuates Chronic Allodynia after Bone Fractures via Reducing Spinal CXCL1/CXCR2-Mediated Iron Accumulation in Mice.
Article in Brain sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed, 5 citations in OpenAlex.
- Degradation products of magnesium implant synergistically enhance bone regeneration: Unraveling the roles of hydrogen gas and alkaline environment.Bioactive materials · 2025Article
- Annexin 1 Reduces Dermatitis-Induced Itch and Cholestatic Itch through Inhibiting Neuroinflammation and Iron Overload in the Spinal Dorsal Horn of Mice.Brain sciences · 2024Article
- Glabridin Therapy Reduces Chronic Allodynia, Spinal Microgliosis, and Dendritic Spine Generation by Inhibiting Fractalkine-CX3CR1 Signaling in a Mouse Model of Tibial Fractures.Brain sciences · 2023Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeNeuroinflammation 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.
methodsA 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.
resultsRepetitive 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.
conclusionsThese 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.
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