Kappa-selective opiate antagonist nor-binaltorphimine improves outcome after traumatic spinal cord injury in rats.

Abstract

Nor-binaltorphimine (nor-BNI) is a recently developed opiate antagonist that has a high degree of selectivity for kappa-opiate receptors. Because of the proposed role of kappa-opiate receptors in mediating secondary damage after spinal trauma, the effect of nor-BNI was studied in a well-characterized model of traumatic spinal cord injury in rats. Nor-BNI, at a dose of 10 mg/kg administered intravenously at 15 min following impact trauma to T-9, significantly improved neurological recovery, measured both in terms of Tarlov motor scores and ability to maintain position on an inclined plane. Given intrathecally, at doses that were ineffective systemically (0.1 mg/kg), nor-BNI also significantly improved neurological recovery after trauma. These data are consistent with the hypothesis that endogenous opioids, through actions at kappa-opiate receptors within the spinal cord, contribute to the pathophysiological changes after spinal trauma that lead to irreversible tissue damage, and indicate that kappa-receptor antagonists may be beneficial for the treatment of acute spinal cord injury.