Insights into the pathophysiology and response of persistent spinal pain syndrome type 2 to spinal cord stimulation: a human genome-wide association study.

BACKGROUND: Spinal cord stimulation (SCS) provides pain relief for some patients with persistent spinal pain syndrome type 2 (PSPS 2), but the precise mechanisms of action and prognostic factors for a favorable pain response remain obscure. This in vivo human genome-wide association study provides some pathophysiological clues. METHODS: We performed a high-density oligonucleotide microarray analysis of serum obtained from both PSPS 2 cases and pain-free controls who had undergone lower back spinal surgery at the study site. Using multivariate discriminant analysis, we tried to identify different expressions between mRNA transcripts from PSPS 2 patients relative to controls, SCS responders to non-responders, or SCS responders to themselves before starting SCS. Gene ontology enrichment analysis was used to identify the biological processes that best discriminate between the groups of clinical interest. RESULTS: Thirty PSPS 2 patients, of whom 23 responded to SCS, were evaluated together with 15 pain-free controls. We identified 11 significantly downregulated genes in serum of PSPS 2 patients compared with pain-free controls and two significantly downregulated genes once the SCS response became apparent. All were suggestive of enhanced inflammation, tissue repair mechanisms and proliferative responses among the former. We could not identify any gene differentiating patients who responded to SCS from those who did not respond. CONCLUSIONS: This study points out various biological processes that may underlie PSPS 2 pain and SCS therapeutic effects, including the modulation of neuroimmune response, inflammation and restorative processes.

Effect of Conventional Spinal Cord Stimulation on Serum Protein Profile in Patients With Persistent Spinal Pain Syndrome: A Case-Control Study.

BACKGROUND: Spinal 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 METHODS: Serum 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. RESULTS: Thirty 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. CONCLUSION: This 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.