Reduction of pathological and behavioral deficits following spinal cord contusion injury with the selective cyclooxygenase-2 inhibitor NS-398

被引:82
作者
Hains, BC
Yucra, JA
Hulsebosch, CE
机构
[1] Univ Texas, Med Branch, MBI, Galveston, TX 77555 USA
[2] Univ Texas, Med Branch, Dept Anat & Neurosci, Galveston, TX 77555 USA
关键词
contusion; COX-2; NS-398; pain; PGE(2); rodent; spinal cord injury;
D O I
10.1089/089771501750170994
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
Spinal cord injury (SCI) results in loss of locomotor function and development of abnormal chronic pain syndromes (mechanical allodynia, thermal hyperalgesia), Following injury, secondary mechanisms including release of excitatory amino acids, inflammation and lipid peroxidation damage neural cells through release of cytotoxic free radicals, We hypothesized that selective inhibition of cyclooxygenase-2 (COX-2), an inducible inflammatory mediator, would decrease tissue damage and subsequently reduce locomotor deficits and development of chronic central pain syndromes after injury. Fifteen minutes prior to receiving T13 spinal segment spinal cord contusion injury, 200-225-g male Sprague-Dawley rats received either vehicle (0.5 ml 1:1 v/v DMSO/saline, i.p., n = 20) or the selective COX-2 inhibitor NS-398 (5 mg/kg in DMSO/saline v/v, i.p., n = 20), Locomotor function via the BBB scale, and nociceptive behaviors measured by paw withdrawals to von Frey filaments and radiant heat stimuli were tested for 4 weeks postinjury, Histological examination and volumetric analysis of spinal cord tissue were performed concomitantly, Spinally contused animals receiving NS-398 demonstrated significantly (p < 0.05) reduced locomotor alteration and reductions in both fore- and hindlimb mechanical allodynia and thermal hyperalgesia when compared to vehicle controls. Histological examination of spinal segments at the lesion segment demonstrated reduced lesion extent and increased viable tissue when compared to vehicle controls. Prostaglandin E-2 levels were significantly lowered in NS-398-treated but not vehicle-treated animals 12 h after injury. These results support the role of COX-2 in reducing pathological and behavioral deficits after spinal cord injury.
引用
收藏
页码:409 / 423
页数:15
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