The fundamental hypothesis for this study is that spinal cord stimulators modulate the excitability of primary afferent neurons to reduce pain, and that these changes can be detected by measurement of axonal excitability. For the primary outcome, we will leverage the sensitivity and reproducibility of threshold tracking nerve conduction studies to detect changes in the excitability of thickly myelinated nerve fibers. We will use microneurography to record directly from primary nociceptive afferents. Finally, we will perform plasma inflammatory cytokine profiles to measure changes due to spinal cord stimulators. By correlating changes in outcome measurements with subject pain levels during therapeutic versus minimal spinal cord stimulators settings, we will determine which effects may be mechanistically relevant and which are unrelated to reduction in pain. Thus, our study will use robust, reproducible techniques to define the peripheral, central, and systemic effects of spinal cord stimulators.
This is a multicenter prospective study in two patient cohorts, namely patients who currently have stably implanted spinal cord simulators. Patients will be randomly assigned to turn on or off their spinal cord stimulators for two week intervals up to six weeks after enrollment, and on the final day of study participation, for two hour intervals, in a multi-crossover design.