Effect of oxidative stress induced by intracranial iron overload on central pain after spinal cord injury
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RESEARCH ARTICLE
Open Access
Effect of oxidative stress induced by intracranial iron overload on central pain after spinal cord injury Fan Xing Meng1,2†, Jing Ming Hou2,3† and Tian Sheng Sun1,2*
Abstract Background: Central pain (CP) is a common clinical problem in patients with spinal cord injury (SCI). Recent studies found the pathogenesis of CP was related to the remodeling of the brain. We investigate the roles of iron overload and subsequent oxidative stress in the remodeling of the brain after SCI. Methods: We established a rat model of central pain after SCI. Rats were divided randomly into four groups: SCI, sham operation, SCI plus deferoxamine (DFX) intervention, and SCI plus nitric oxide synthase (NOS) inhibitor treatment. Pain behavior was observed and thermal pain threshold was measured regularly, and brain levels of iron, transferrin receptor 1 (TfR1), ferritin (Fn), and lactoferrin (Lf), were detected in the different groups 12 weeks after establishment of the model. Results: Rats demonstrated self-biting behavior after SCI. Furthermore, the latent period of thermal pain was reduced and iron levels in the hind limb sensory area, hippocampus, and thalamus increased after SCI. Iron-regulatory protein (IRP) 1 levels increased in the hind limb sensory area, while Fn levels decreased. TfR1 mRNA levels were also increased and oxidative stress was activated. Oxidative stress could be inhibited by ferric iron chelators and NOS inhibitors. Conclusions: SCI may cause intracranial iron overload through the NOS–iron-responsive element/IRP pathway, resulting in central pain mediated by the oxidative stress response. Iron chelators and oxidative stress inhibitors can effectively relieve SCI-associated central pain. Keywords: Central pain, Spinal cord injury, Iron, Oxidative stress
Background Spinal cord injury (SCI) refers to pathological changes including motor, sensory, and sphincter dysfunction and dystonia, as well as pathological reflexes of the corresponding spinal segment following damage by direct or indirect factors. Previous studies have concentrated on the recovery of motor and sensory functions and have tended to ignore SCI-associated complications. However, central pain is a common complication of SCI, with an incidence as high as 77–86% [1, 2]. Central pain (CP) is a neuropathic syndrome associated with hypersensitivity * Correspondence: [email protected] † Equal contributors 1 Third Military Medical University, No. 30 Gaotanyan Street, 400038 Chongqing, China 2 Department of Orthopedics, Chinese PLA Army General Hospital, Dongcheng District, Nanmencang No. 5, 100700 Beijing, China Full list of author information is available at the end of the article
to pain caused by spinal cord or brain injury. It is often associated with persistent and intolerable lower limb pain [3, 4], which can seriously affect sleep, self-care, rehabilitation, and quality of life. However, the pathogenesis of CP is unclear and only empirical therapy can be applied, leading to pain relief in only 20–30% of patients [5]
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