Psychometric and Molecular Profiling to Predict Outcomes of Spinal Cord Stimulation for Chronic Pain: A Pilot Study

Simona D’Agnelli,1,* Giada Amodeo,2,* Marco Cascella,3 Marco Baciarello,1 Valentina Bellini,1 Silvia Franchi,2 Giulia Galimberti,2 Paola Sacerdote,2 Elena Giovanna Bignami1 1Anesthesiology, Critical Care and Pain Medicine Division, Department of Medicine and Surgery, University of Parma, Parma, 43126, Italy; 2Pain Therapy and Neuroimmunology Unit, Department of Pharmacological and Biomolecular Sciences “Rodolfo Paoletti”, Università Degli Studi Di Milano, Milano, 20129, Italy; 3Unit of Anesthesiology, Intensive Care Medicine, and Pain Medicine, Department of Medicine, Surgery, and Dentistry, University of Salerno, Salerno, 84082, Italy*These authors contributed equally to this workCorrespondence: Paola Sacerdote, Email [email protected]: Spinal cord stimulation (SCS) is a well-established intervention for chronic pain, but the factors predicting treatment success remain unclear. This pilot study investigated psychometric and inflammatory biomarkers associated with clinical outcomes in patients undergoing SCS for chronic low back pain.Patients and Methods: Twenty-two eligible patients were enrolled. Clinical evaluations, psychometric assessments, and blood samples were collected at baseline and at 1-, 3-, and 6-month post-implantation. Pain intensity, psychological status, and quality of life were assessed using validated questionnaires. Inflammatory markers were analyzed in peripheral blood mononuclear cells (PBMCs) at both mRNA and protein levels.Results: Nineteen patients completed the trial and received definitive SCS implantation (Trial Completed, TC group), while three were discontinued (Trial Failed, TF group). In the TC group, pain intensity and its interference with emotional and work life significantly improved. Psychometric scores also improved: pain catastrophizing decreased below the clinical threshold, and anxiety and depression scores were significantly reduced, alongside enhanced quality of life. Greater pain relief at follow-up was associated with lower pre-implant anxiety and depression levels. Cytokine analysis revealed downregulation of pro-inflammatory IL-1β and upregulation of anti-inflammatory IL-10 and IL-4 post-SCS. In the TF group, baseline depression was higher compared to the TC group. SCS trial implantation in these patients induced only IL-4 upregulation, without broader cytokine modulation.Conclusion: SCS significantly improved clinical and psychometric outcomes and positively modulated inflammatory profiles in patients with chronic low back pain. High baseline depressive symptoms may predict poorer SCS outcomes, suggesting the importance of psychological assessment in patient selection.Keywords: spinal cord stimulation, chronic pain, psychometric variables, quality of life, inflammatory markers, cytokines