Abstract
Lumbar spinal stenosis (LSS) causes ischemia, inflammation, demyelination and results in dysfunction of the cauda equina (CE), leading to pain and locomotor functional deficits. We investigated whether exogenous administration of S-nitrosoglutathione (GSNO), an endogenous redox modulating anti-neuroinflammatory agent, hastens functional recovery in a CE compression (CEC) rat model. CEC was induced in adult female rats by the surgical implantation of two silicone blocks within the epidural spaces of L4-L6 vertebrae. GSNO (50 μg/kg body weight) was administered by gavage 1 h after the injury, and the treatment was continued daily thereafter. GSNO induced change in the pain threshold was evaluated for four days after the compression. Tissue analyses and locomotor function evaluation were carried out at two weeks and four weeks after the CEC respectively. GSNO significantly improved motor function in CEC rats as evidenced by an increased latency on rotarod compared with vehicle-treated CEC rats. CEC induced hyperalgesia was decreased by GSNO. GSNO also increased the expression of VEGF, reduced cellular infiltration (H&E staining) and apoptotic cell death (TUNEL assay), and hampered demyelination (LFB staining and g-ratio). These data demonstrate that administration of GSNO after CEC decreased inflammation, hyperalgesia and cell death leading to improved locomotor function of CEC rats. The therapeutic potential of GSNO observed in the present study with CEC rats suggests that GSNO is a candidate drug to test in LSS patients.
Highlights
Lumbar spinal stenosis (LSS) is a stable disorder with mild to severe disability and neurological deficits
The present study shows that GSNO-treated CEC animals (GSNO) treatment after the onset of LSS ameliorated motor dysfunction, reduced hyperalgesia, and inhibited tissue degeneration
The protection was offered through inhibiting cellular infiltration, decreasing demyelination and apoptotic cell death, and increasing the expression of VEGF
Summary
Lumbar spinal stenosis (LSS) is a stable disorder with mild to severe disability and neurological deficits. LSS is one of the most frequent reasons for spinal surgery associated with chronic low back pain in the elderly population. In the US, 90 out of 100,000 persons older than 60 years undergo LSS related spinal surgery every year [1]. The socioeconomic burden due to LSS is huge and has been increasing rapidly, despite considerable technological advances in diagnosis [2,3]. LSS compresses cauda equina (CE) fibers over time and results in intermittent claudication/pseudoclaudication [4]. CEC results in neurodegeneration and neuronal dysfunction through Wallerian-degeneration [5,6]. LSS-induced CEC interrupts normal spinal microvascular circulation [7,8], and leads to secondary tissue damage from hypoxia/ischemia injury. Secondary damage augments inflammation-mediated neuronal damage to the CE fibers and spinal cord.
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