Abstract
BackgroundCentral 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.MethodsWe 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.ResultsRats 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.ConclusionsSCI 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.
Highlights
Central pain (CP) is a common clinical problem in patients with spinal cord injury (SCI)
paw-withdrawal latency (PWL) were higher in the sham operation group at all time points compared with the other groups, while PWLs were lowest in the SCI group (Fig. 1b)
Recent studies have indicated that certain brain regions, such as the somatosensory center, thalamus, and limbic system, undergo remodeling after SCI to compensate for the loss of sensory function below the injured segment, and many researchers believe that this remodeling may be a key factor in SCI-associated CP [25, 26]
Summary
Central pain (CP) is a common clinical problem in patients with spinal cord injury (SCI). We investigate the roles of iron overload and subsequent oxidative stress in the remodeling of the brain after SCI. Previous studies have concentrated on the recovery of motor and sensory functions and have tended to ignore SCI-associated complications. The mechanisms of SCI-associated central pain are currently unclear, and the numerous hypotheses proposed to date have been unable to explain fully the mechanisms responsible for structural and functional remodeling in the brains of patients with CP [6]. Increasing evidence suggests that structural and functional remodeling of the brain is a key causative factor in SCI-associated CP [7, 8].
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