Effect of oxidative stress induced by intracranial iron overload on central pain after spinal cord injury.

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.

• Authors: Fan Xing Meng, Jing Ming Hou, Tian Sheng Sun
• Journal: Journal of orthopaedic surgery and research (J Orthop Surg Res) Vol. 12 Issue 1 Pg. 24 (Feb 08 2017) ISSN: 1749-799X [Electronic] England
• PMID: 28178997 (Publication Type: Journal Article)

Chemical References

• Receptors, Transferrin
• Tfrc protein, rat
• Malondialdehyde
• Ferritins
• Iron
• Superoxide Dismutase
• Lactoferrin
• Iron Regulatory Protein 1

Topics

• Animals
• Brain (metabolism)
• Female
• Ferritins (metabolism)
• Iron (metabolism)
• Iron Overload (complications, metabolism, physiopathology)
• Iron Regulatory Protein 1 (metabolism)
• Lactoferrin (metabolism)
• Malondialdehyde (metabolism)
• Oxidative Stress (physiology)
• Pain (etiology, metabolism, physiopathology)
• Pain Measurement (methods)
• Pain Threshold (physiology)
• Rats, Sprague-Dawley
• Receptors, Transferrin (metabolism)
• Spinal Cord Injuries (complications, metabolism, physiopathology)
• Superoxide Dismutase (metabolism)