This is a multicenter prospective study of 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 one hour intervals, in a multi-crossover design. In a subset of patients we will also perform combined positron emission tomography/magnetic resonance imaging at baseline, week 2 and week 4.
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, the study investigators will leverage the sensitivity and reproducibility of threshold tracking nerve conduction studies to detect changes in the excitability of thickly myelinated nerve fibers. The study investigators will use microneurography to record directly from primary nociceptive afferents. Finally, the study investigators 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, this study will determine which effects may be mechanistically relevant and which are unrelated to reduction in pain. Thus, this study will use robust, reproducible techniques to define the peripheral, central, and systemic effects of spinal cord stimulators.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
QUADRUPLE
Enrollment
180
Patients in this intervention group will have their spinal cord stimulator turned off or to the minimal settings possible.
Patients in this intervention group will have their spinal cord stimulator turned on to their usual stimulation settings.
Patients with imaging compatible devices will undergo positron emission tomography/magnetic resonance imaging at three time points during the study. This imaging involves administration of the \[11C\]PBR28 radioligand, which is an investigational drug. Only a subset of patients who have 3 Tesla magnetic resonance imaging compatible stimulators will undergo this imaging.
Massachusetts General Hospital
Boston, Massachusetts, United States
RECRUITINGBeth Israel Deaconess Medical Center
Boston, Massachusetts, United States
RECRUITINGBrigham and Women's Hospital
Boston, Massachusetts, United States
RECRUITINGSupraexcitability
The primary outcome will be superexcitability (indicating paired pulse facilitation) measured by threshold tracking nerve conduction.
Time frame: From baseline (enrollment) to six weeks
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