Neuroimaging Biomarkers of Pain Therapy with Spinal Cord Stimulation Using Resting State Near-infrared Spectroscopy Connectivity

Introduction: Spinal Cord Stimulation (SCS) has been used for over 4 decades with varied efficacy for treatment of intractable neuropathic pain. Supraspinal therapeutic mechanisms of SCS are important to elucidate but currently poorly understood. Our study explored the relationship between changes in resting state functional connectivity (rsFC) during SCS treatment in patients during SCS trial and in SCS chronic users. The overarching goal of this line of inquiry is to refine targeting of pain treatment through understanding of brain mechanisms utilizing mobile bedside neuroimaging methods.

Methods: We enrolled 12 chronic SCS users (at least 6 months) who reported effective pain relief based on changes in pain scores and SCS utilization and 9 patients undergoing SCS trial. Pain-assessment scales and resting state functional NIRS connectivity between 7 cortical regions (medial prefrontal(mPFC), right and left dorsolateral prefrontal(DLPFC), sensorimotor(SMC) and posterior parietal(PPC) cortices) were collected during two sessions. Data was collected for chronic SCS users, with SCS “on” (session 1) and following a 3-5 day washout period where SCS was off (session 2); for trial SCS patients, data was collected before the trial implant (session 1) and after 7 days of SCS trial (session 2). Data analyses included multivariable linear mixed-effects models and regularized LASSO regression.

Results: Participants were 63.6(13.6) y/o and 86% male. Pain relief with SCS in chronic and trial users, respectively, was as follows: Patient Global Impression of Change Likert scale 5(1.2) and 5.6(1.1); best Numeric Pain Rating Score over last 24 hours reduced by 1.2(2.1) and 2.4(2.5) points, and Pain-Detect scale improved by 0.9(3.8) and 4.1(2.3). For chronic SCS users, reduced connectivity between rightDLPFC and mPFC was associated with SCS use. For SCS trial patients, SCS use was associated with higher connectivity for the following regional pairs: rightDLPFC-leftDLPFC, rightDLPFC-rightSMC and leftSMC-leftPPC. Pain reduction with SCS in chronic users measured with Pain-Detect score was associated with decreased connectivity for the following pairs: rightSMC-rightPPC and rightSMC-leftPPC. For the SCS trial patients, pain reduction according to Pain-Detect score was associated with increased connectivity between leftDLPFC-leftSMC. Finally, for SCS trial patients, lower connectivity prior to SCS trial between leftDLPFC-leftSMC and leftSMC-right PPC was associated with pain relief measured with Pain-Detect scale.

Conclusion: Pain relief with SCS is associated with specific brain connectivity signatures for chronic and trial SCS users. These findings are encouraging preliminary steps toward understanding of the brain mechanisms of pain and it’s treatment utilizing mobile neuroimaging technology.