Alpha Oscillations and Conditioned Pain Modulation Is Associated With Treatment Resistance to Spinal Cord Stimulation for Neuropathic Pain

BACKGROUND: Neuropathic pain (NP) is a severe form of chronic pain associated with reduced quality of life. Spinal cord stimulation (SCS) can provide pain relief for some but not all treated, highlighting the importance of predictive markers. Previous studies have found that individuals with NP have abnormal alpha oscillations detected by resting state magnetoencephalography (MEG) and altered conditioned pain modulation (CPM). In the current study, we tested whether these measures predicted SCS outcome. METHODS: Forty patients with NP (22F, 18 M) were evaluated before a 12-day trial of SCS including pain self-reports, CPM, magnetic resonance imaging (MRI) and 5-min MEG scans to evaluate alpha oscillations (8-13 Hz) in the dynamic pain connectome. Those with ≥ 30% pain reduction post-trial were considered treatment responders. Twenty-nine age- and sex-matched healthy controls (HC) (17F, 12 M) also underwent CPM testing and MEG. RESULTS: Half of the patients treated were classified as responders based on reduced pain intensity. Responders also had significantly improved quality of life compared to nonresponders. There were 2 key findings from the pre-SCS testing: (1) Pain relief following SCS significantly correlated with lower alpha power in nodes of the salience network and ascending nociceptive pathway; this relationship demonstrated regionally specific sex trends; and (2) Nonresponders exhibited significantly abnormal inefficient CPM (whole spectrum or inhibitory) and reduced peak alpha frequency in the subgenual anterior cingulate cortex, which had a strong effect size. CONCLUSIONS: Abnormal brain-behaviour features involving alpha oscillations and CPM may underlie the ineffectiveness of SCS to treat NP. SIGNIFICANCE STATEMENT: These findings not only build on our fundamental understanding of the individual variability and abnormalities in brain-behavioural measures in NP but also demonstrate their potential predictive value when considering personalised pain management with SCS treatment and potential neural targets for those resistant to SCS.