How and when does peripheral input affect recovery after SCI
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Prior work has shown that peripheral stimulation can affect plasticity within the lumbosacral spinal cord in rats that have undergone a thoracic transection. Both variable intermittent shock and peripheral inflammation inhibit adaptive plasticity and sensitize pain (nociceptive) responses to mechanical stimulation (enhanced mechanical reactivity [EMR]). These effects are observed when peripheral stimuli are noxious and engage C-fibers. We have shown that these same experimental manipulations impair recovery after a contusion injury. However, in contused animals, a much broader range of stimuli appear to affect spinal function, including stimulation that is sub-threshold for engaging C-fibers. We propose that a contusion injury fundamentally alters how the system responds to peripheral stimulation applied below the injury. Aim 1 will define the circumstances under which peripheral stimulation affects spinal function and the fibers types involved, using both variable intermittent shock and a treatment that induces peripheral inflammation (application of the irritant capsaicin). We predict that less intense stimulation, that has no effect on spinal function in spinally-transected rats, will enhance tissue loss and impair recovery after a contusion injury. Aim 2 will explore the cellular mechanisms that underlie stimulation-induced tissue loss..........