• Gustavo Fabregat-Cid, David L Cedeño, Anushik Harutyunyan, Raquel Rodríguez-López, Vicente Monsalve-Dolz, Ana Mínguez-Martí, María José Hernández-Cádiz, Natalia Escrivá-Matoses, Vicente Villanueva-Pérez, Asensio SamperJuan MarcosJMMultidisciplinary Pain Management Department, University General Hospital, Valencia, Spain; Surgery Department, Medical School, University of Valencia, Valencia, Spain., José De Andrés, and Ricardo Vallejo.
• Multidisciplinary Pain Management Department, University General Hospital, Valencia, Spain; Surgery Department, Medical School, University of Valencia, Valencia, Spain. Electronic address: gfabregat@gmail.com.
• Neuromodulation. 2023 Oct 1; 26 (7): 144114491441-1449.

BackgroundSpinal cord stimulation (SCS) provides pain relief for most patients with persistent spinal pain syndrome type 2 (PSPS 2). Evidence is mounting on molecular changes induced by SCS as one of the mechanisms to explain pain improvement. We report the SCS effect on serum protein expression in vivo in patients with PSPS 2.Materials And MethodsSerum proteins were identified and quantified using mass spectrometry. Proteins with significantly different expression among patients with PSPS 2 relative to controls, responders, and nonresponders to SCS, or significantly modulated by SCS relative to baseline, were identified. Those most correlated with the presence and time course of pain were selected using multivariate discriminant analysis. Bioinformatic tools were used to identify related biological processes.ResultsThirty patients with PSPS 2, of whom 23 responded to SCS, were evaluated, together with 14 controls with no pain who also had undergone lumbar spinal surgery. A significant improvement in pain intensity, disability, and quality of life was recorded among responders. Five proteins differed significantly at baseline between patients with PSPS 2 and controls, with three proteins, mostly involved in immune processes and inflammation, being downregulated and two, mostly involved in vitamin metabolism, synaptic transmission, and restorative processes, being upregulated. In addition, four proteins, mostly related to immune processes and inflammation, decreased significantly, and three, mostly related to iron metabolism and containment of synaptic sprouting, increased significantly during SCS.ConclusionThis study identifies various biological processes that may underlie PSPS 2 pain and SCS therapeutic effects, including the modulation of neuroimmune response and inflammation, synaptic sprouting, vitamin and iron metabolism, and restorative processes.Copyright © 2023 International Neuromodulation Society. Published by Elsevier Inc. All rights reserved.

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