Chronic, selective forebrain responses to excitotoxic dorsal horn injury

Intraspinal injection of the AMPA/metabotropic receptor agonist quisqualic acid (QUIS) results in excitotoxic injury which develops pathological chara cteristics similar to those associated with ischemic and traumatic spinal c ord injury (SCI) (R. P. Yezierski et at, 1998, Pain 75: 141-155; R, P. Yezi erski ct at, 1993, J. Neurotrauma 10: 445-456), Since spinal injury can lea d to partial or complete deafferentation of ascending supraspinal structure s, it is likely that secondary to the disruption of spinal pathways these r egions could undergo significant reorganization. Recently, T. J. Morrow et at. (Pain 75: 355-365) showed that autoradiographic estimates of regional c erebral blood flow (rCBF) can be used to simultaneously identify alteration s in the activation of multiple forebrain structures responsive to noxious formalin stimulation. Accordingly, we examined whether excitotoxic SCI prod uced alterations in the activation of supraspinal structures using rCBF as a marker of neuronal activity. Twenty-four to 41 days after unilateral inje ction of QUIS into the T12 to L3 spinal segments, we found significant incr eases in the activation of 7 of 22 supraspinal structures examined. As comp ared to controls, unstimulated SCI rats exhibited a significant bilateral i ncrease in rCBF within the arcuate nucleus (ARC), the hindlimb region of S1 cortex (HL), parietal cortex (PAR), and the thalamic posterior (PO), ventr al lateral (VL), ventral posterior lateral (VPL), and ventral posterior med ial (VPM) nuclei. All structures showing significantly altered rCBF are ass ociated with the processing of somatosensory information. These changes con stitute remote responses to injury and suggest that widespread functional c hanges occur within cortical and subcortical regions following injury to th e spinal cord. (C) 2000 Academic Press.