Maladaptive plasticity following spinal cord injury

University Of Maryland Baltimore, Baltimore MD

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Abstract

Insults to the brain and spinal cord result not only in debilitating motor, sensory and cognitive deficits, but also in chronic, excruciating and relentless pain that is largely resistant to treatment. In most patients, pain starts weeks or months after the original insult, and includes increased pain with noxious stimulation (hyperalgesia), pain in response to previously innocuous stimuli (allodynia), and spontaneous pain. Spinal cord lesions typically produce particularly painful CPS symptoms, with unremitting pain that can be diffuse, bilateral, and may extend, "below-lesion", to locations caudal to the spinal injury. The delayed expression of CPS and the diffuse localization of painful symptoms suggest that the pathophysiology does not reflect only direct effects at the denervated spinal segments. Rather, these features of CPS strongly suggest the occurence of maladaptive plasticity in supraspinal structures at which inputs from various body parts converge, 'The ultimate goal of this application is to identify the factors that are causally responsible for this maladaptive plasticity following spinal cord injury. To this end, we adapted a rodent spinal cord injury model of CPS. We demonstrated that rats suffering from CPS have abnormally high neuronal activity in the posterior nucleus of the thalamus (PO). We also demonstrated that the activity of PO, and related thalamic nuclei, is tightly regulated by inhibitory inputs from the zona incerta and the anterior pretectal .nucleus. These findings suggest that CPS is associated with maladaptive plasticity in the incerto-thalamic pathway. Based on these exciting new findings, we propose that CPS can result from suppressed inhibition to thalamic.nuclei from zona incerta and the anterior pretectal nucleus. The proposed studies will use electrophysiological, behavioral and anatomical approached to test the validity of 4 key predictions that emerge from our overarching hypothesis.