• Jose De Andrés, Francisco Navarrete-Rueda, Gustavo Fabregat, Maria Salud García-Gutiérrez, Vincente Monsalve-Dolz, Anushik Harutyunyan, Ana Mínguez-Martí, Raquel Rodriguez-Lopez, and Jorge Manzanares.
• Anesthesia Unit-Surgical specialties department. Valencia University Medical School. Department of Anesthesiology, Critical Care and Pain Management. General University Hospital, Valencia, Spain.
• Neuromodulation. 2021 Jan 1; 24 (1): 49-60.

ObjectiveThe use of spinal cord stimulation for patients with failed back surgery syndrome (FBSS) is very common. In order to better understand the mechanisms of action of spinal cord stimulation (SCS), our aim was to determine potential changes in relative gene and protein expression in the peripheral blood mononuclear cells (PBMCs) of patients as potential biomarkers of disease outcomes and potential new targets for therapy.MethodsTwenty-four patients with diagnosis of FBSS refractory to conservative therapy for at least six months were included in the study. Clinical evaluation in this study included validated questionnaires. Blood samples (10 mL) were collected five times from baseline until two months after implant of the leads. Proenkephalin (PENK), cannabinoid receptors CB1 and CB2, and interleukin 1β (IL 1β) were analyzed. Each patient served as his/her own control by comparing the samples collected at different time points against the baseline sample collected at T0.ResultsA total of 16 patients met all relevant criteria during the whole study and were assessed. Only PENK showed significant changes over time (Friedman p = 0.000). A positive correlation was observed between changes in visual analog scale (VAS) scores and PENK and a negative correlation between changes in PENK and Short Form-12 (SF-12) mental component score (MCS) scores, as well as between changes in IL 1β and Pain Detect Questionnaire (PD-Q) scores. As PENK changes increased, so did pain (VAS). As changes in PENK increased, SF-12 MCS health worsened. As changes in IL 1β increased, PD-Q values decreased. No severe adverse events occurred.ConclusionsPreviously unknown effects of SCS on levels of PBMCs biomarkers are demonstrated. The findings of our research suggest a potential for useful integration of genome analysis and lymphocyte expression in the daily practice of neurostimulation for pain management and represent a novel road map in the light of the important questions that remain unanswered.© 2020 International Neuromodulation Society.

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