Effect of oxidative stress induced by intracranial iron overload on central pain after spinal cord injury.
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.
Third Military Medical University, No. 30 Gaotanyan Street, 400038, Chongqing, China.|Department of Orthopedics, Chinese PLA Army General Hospital, Dongcheng District, Nanmencang No. 5, 100700, Beijing, China.
Fan Xing
FX
Meng
Department of Orthopedics, Chinese PLA Army General Hospital, Dongcheng District, Nanmencang No. 5, 100700, Beijing, China.|Southwest Hospital, Third Military Medical University, No. 30 Gaotanyan Street, 400038, Chongqing, China.
Jing Ming
JM
Hou
Third Military Medical University, No. 30 Gaotanyan Street, 400038, Chongqing, China. suntiansheng-@163.com.|Department of Orthopedics, Chinese PLA Army General Hospital, Dongcheng District, Nanmencang No. 5, 100700, Beijing, China. suntiansheng-@163.com.
Tian Sheng
TS
Sun
D000818:Animals; D001921:Brain / Q000378:metabolism; D005260:Female; D005293:Ferritins / Q000378:metabolism; D007501:Iron / Q000378:metabolism; D019190:Iron Overload / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D035941:Iron Regulatory Protein 1 / Q000378:metabolism; D007781:Lactoferrin / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D010146:Pain / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D010147:Pain Measurement / Q000379:methods; D017288:Pain Threshold / Q000502:physiology; D017207:Rats, Sprague-Dawley; D011990:Receptors, Transferrin / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D013482:Superoxide Dismutase / Q000378:metabolism
D011990:Receptors, Transferrin; C545564:Tfrc protein, rat; D008315:Malondialdehyde; D005293:Ferritins; D007501:Iron; D013482:Superoxide Dismutase; D007781:Lactoferrin; D035941:Iron Regulatory Protein 1
Central pain; Iron; Oxidative stress; Spinal cord injury