Phenotyping Response to Spinal Cord Stimulation in Chronic Low Back Pain

Chronic low back pain (CLBP) is a debilitating condition and costly to treat. Long-term drug treatment often fails due to habituation, breakthrough of pain, or adverse effects of drug treatment. Opioid use to manage this pain has contributed to the opioid epidemic. Spinal cord stimulators have emerged as a promising treatment and reduces reliance on drugs. However, response to spinal cord stimulation (SCS) is unpredictable. It is difficult to predict which patients will respond positively to SCS because the physiological mechanism for treatment responsiveness is unclear. Therefore, the aim of this study is to investigate how spinal cord stimulators affect functional measures in patients with CLBP, including functional MRI, neurophysiology, gait analysis, and questionnaires. The results of this study can lead to the widespread adoption of spinal cord stimulators as a safe and effective therapy for CLBP, reducing the reliance on opioids and mitigating the opioid epidemic's impact.

Electrical stimulation of neural tissues can be effective and reduce reliance on drugs, and epidural spinal cord stimulation (SCS) is often used to treat chronic low back pain (CLBP). Despite a half-century of clinical use, the mechanism of action of SCS remains unclear. Many patients fail to respond to SCS, and lacking a thorough understanding of the biological processes underlying SCS, there are no established predictors of treatment response to SCS. The application of SCS today is dependent on an empirical trial-and-error approach, which is expensive, time consuming, and frustrating for the patient. Even with the advent of improved stimulation technology and novel stimulation strategies (e.g., high frequency, burst stimulation, etc.), device failure rates remain high. CLBP is a multi-faceted process involving abnormal processing in the sensorimotor cortices, prefrontal cortex, insula, thalamus, limbic system, cerebellum, and brainstem nuclei including the periaqueductal gray, locus coeruleus, and dorsal raphe nuclei, all of which function in the context of myriad individual psychosocial factors.

The goal of this study is to develop a quantitative description of the neurophysiological processes associated with the sensation of pain and identify the signature(s) of pain, the neurophysiological pain connectome (NPC), that may guide treatment more effectively. The investigators hypothesize CLBP is marked by a pattern of pathological activity resulting from interactions among different brain networks. The investigators theorize the spatiotemporal patterns of activity among these networks, which are reflected in the NPC, are maladaptive and expressed as abnormal cognitive, affective, and sensorimotor expressions of chronic pain. Because CLBP is a complex disorder, a fundamentally different approach is necessary to assess the many facets of the NPC using comprehensive multi-modal assessments.

Investigators will use: 1. functional and diffusion MRI to quantify brain functional and microstructural connectivity; 2. electroencephalography (EEG); 3. gait kinematics; and 4. electrophysiology (somatosensory evoked potential, SSEP and pain-related evoked potentials, PREPs) to evaluate the neurotransmission of pain. Investigators will then correlate patterns in the NPC with a range of patient-reported outcomes including the domains of the PROMIS questionnaires, and combine this information to generate models based on the patterns in the NPC most closely associated with specific aspects of pain and the patient experience.