Abstract
Abstract : The majority of patients with spinal cord injury (SCI) develop intractable chronic neuropathic pain that is resistant to conventional pharmacologic treatments. An alternative and potentially effective modality of treatment motor cortex stimulation (MCS) offers hope for these patients. The purpose of this application is to elucidate the neurobiological basis of reduced pain following MCS. We propose that MCS reverses hyperalgesia by enhancing the activity in the GABAergic nucleus zona incerta (ZI), and therefore inhibiting pain processing in the posterior thalamus (PO). Using single cell extracellular electrophysiological recordings from the thalamus of rats with SCI-pain we tested the effect of MCS on the activity of neurons in ZI and PO. We demonstrated last year that MCS significantly enhanced spontaneous and evoked responses in the majority of PO-projecting ZI neurons and caused a significant and robust suppression of activity in PO. We now report that inactivation of ZI using muscimol (GABAA agonist) blocks the effects of MCS stimulation on PO neurons while cutting the pyramidal tracts have no effects on suppressed activity in PO after MCS. These findings further support our overarching hypothesis that MCS alleviates pain by activating the incerto-thalamic pathway.
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