| dc.description.abstract | Pain input after spinal cord injury can be detrimental to acute and long-term processes. In a rodent model of incomplete spinal cord injury, it has been shown that nociceptive stimulation (pain input) administered below the injury can exacerbate secondary injury mechanisms, increasing tissue loss and expanding hemorrhage. Recent data suggests that supraspinal signals are involved in the development of secondary injury and long-term locomotor deficits. In this dissertation, I explored the role of brain-dependent processes in the development of hemorrhage at the spinal cord lesion site.
I first examined whether communication with the brain is required to induce hemorrhage and engage a cardiovascular response. Rats received a lower thoracic (T10- 11) contusion injury followed by a rostral (T2) transection. A day after the contusion injury, nociceptive fibers were engaged by applying electrical stimulation (shock) to the tail or the irritant capsaicin to one hind paw. Noxious stimulation increased hemorrhage at the site of injury. This effect, and the rise in blood pressure/flow elicited by shock, were blocked by a rostral transection. Further, pharmacologically inducing a rise blood pressure with norepinephrine did not promote hemorrhage.
To explore whether noxious stimulation increases the permeability of the blood spinal cord barrier (BSCB), contused rats were injected with Evans blue. Exposure to shock allowed Evan’s blue to enter the area of injury and this effect was blocked by a rostral transection.
The remaining experiments examined whether the adverse effects of noxious stimulation are driven by a brain-mediated pain state. Inhibiting pain with morphine did not attenuate the shock-induced hemorrhage or decline in locomotor performance. When the same noxious stimulus was applied rostral versus caudal to injury, only the latter produced evidence of increased hemorrhage. It was unclear, however, whether stimulation above the site of injury induced a comparable level of pain. To address this issue, a new procedure was developed wherein shock intensity was modified so that it elicited a comparable brain-dependent (vocalization) response. After verifying that shock at vocalization threshold induces hemorrhage when given caudal to injury, I assessed the effect of stimulation applied rostral to injury. Again, it did not induce hemorrhage. | |
