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

Spinal cord injury (SCI) results in loss of locomotor function and developm ent of abnormal chronic pain syndromes (mechanical allodynia, thermal hyper algesia), Following injury, secondary mechanisms including release of excit atory 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 an d development of chronic central pain syndromes after injury. Fifteen minut es 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 n ociceptive behaviors measured by paw withdrawals to von Frey filaments and radiant heat stimuli were tested for 4 weeks postinjury, Histological exami nation and volumetric analysis of spinal cord tissue were performed concomi tantly, Spinally contused animals receiving NS-398 demonstrated significant ly (p < 0.05) reduced locomotor alteration and reductions in both fore- and hindlimb mechanical allodynia and thermal hyperalgesia when compared to ve hicle controls. Histological examination of spinal segments at the lesion s egment demonstrated reduced lesion extent and increased viable tissue when compared to vehicle controls. Prostaglandin E-2 levels were significantly l owered 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 behav ioral deficits after spinal cord injury.