Spinal cord injury and other insults to the central nervous system frequently result in central pain syndrome (CPS), a severe, treatment-resistant chronic pain disorder. The mechanisms of CPS are poorly understood and must be better characterized before effective therapies can be developed. In a rodent spinal cord injury model of CPS, we recently found that CPS was associated with abnormally increased activity in the posterior thalamic nucleus (PO). Pain perception requires activity in a network of regions in the cerebral cortex, several of which receive afferent input from PO;thus, pain associated with CPS may result from abnormal activity in the cortical targets of PO. This proposal aims to test the hypothesis that CPS is associated with increased input from PO to the primary (S1) and second (S2) somatosensory cortical areas;three specific predictions arising from this hypothesis will be tested in our rodent model of CPS. First, electrophysiological recordings will be obtained to test the prediction that S1/S2 neurons that receive PO input show increased activity in CPS rats compared to shams. Second, electrophysiological recordings will be obtained in awake, behaving rats to test the prediction that CPS-related behavioral changes that develop after spinal cord injury are correlated with changes in neuronal activity in PO and S1/S2. Third, electrophysiological recordings will be obtained in CPS rats during administration of GABA receptor agonists into PO to test the prediction that inactivation of PO will suppress CPS-related increases in cortical responses. PUBLIC HEALTH RELEVANCE CPS potentially affects millions of people worldwide and poses a significant clinical problem due to its resistance to treatment. At best, current therapies for CPS can reduce pain for short periods of time but cannot eliminate it completely. The proposed project will provide novel data that should improve understanding of the pathophysiological mechanisms underlying CPS and aid in the development of more effective treatments for this debilitating disorder.