Suprasacral spinal cord injury (SCI) often results in paraplegia (~45-50%). A great deal of research has been devoted to enabling walking in paraplegics. In addition to limited mobility and the sequelae of maladies that derive from it, pelvic visceral dysfunction following suprasacral SCI adds dramatically to both the morbidity and mortality of SCI survivors. Aberrant reflexes develop following initial spinal shock from organs distal to the injury; not only are excitatory reflex pathways exaggerated (i.e. hyper-reflexic), they are also indiscriminate (so- called mass reflexes). In fact, anything innervated by spinal motor neurons distal to the spinal cord lesion usually becomes hyper-reflexic following initial spinal shock due to both lack of descending inhibition and sprouting of uninhibited afferent nerves. These mass reflexes emerge and result in reflex pathways that were once inhibitory becoming excitatory, such as is the case in suprasacral SCI wherein noxious stimulation of the perineum inhibits bladder activity normally, but stimulates it after injury. Moreover, the emergence of entirely novel reflexes may occur distal to any SCI (e.g. interlimb reflexes in cervical SCI14 and bladder-to-hind limb locomotor reflexes in suprasacral SCI). The emergence of a bladder-to-hind limb locomotor reflex is the observation that forms the basis of this proposal. It can be readily observed during cystometric evaluation in animals that minimally void by this mechanism (rat type 2 pattern) following suprasacral SCI, as well as during high pressure non-voiding contractions, and during routine external crede as part of daily post-SCI care. This apparently intravesical pressure-driven vesicosomatic reflex, an aberrant reflex pathway that develops following suprasacral SCI, may be utilized in order to facilitate walking in these animals. The overarching hypothesis is that neurostimulation of sacral visceral afferents, delivered as a surrogate stimulus for intravesical high pressure events, will facilitate hind limb locomotor activity in suprasacral SCI rats. We will utilize chronic SCI rats with known urinary bladder hyper-reflexia to selectively activate hind lim locomotor activity using our method of sacral neurostimulation (SNS) in combination with our model of SCI to demonstrate the utility of this approach. The long term goals of this project are to utilize this aberrant reflex pathway to facilitate walking training and augment walking capability in paraplegic patients by developing and applying appropriate neuromodulatory strategies directed toward utilization of this reflex therapeutically.
This research will enhance our understanding of the development of aberrant reflexes following spinal cord injury and will simultaneously provide information regarding the potential to harness such reflexes for improving the quality of life for patients with spinal cord injury. If we can demonstrate that sacral neuromodulation might facilitate hind limb reflex activation of the spinal locomotor central pattern generator in a manner similar to high intravesical pressures, then we can simultaneously bypass these high pressures using sacral neurostimulation and treat the high intravesical pressures, thereby potentially facilitating assisted walking while treating lower urinary tract dysfunction.
