{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T05:23:57Z","timestamp":1793683437240,"version":"4.5.1"},"reference-count":53,"publisher":"BMJ","issue":"10","funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI16\/01364"],"award-info":[{"award-number":["PI16\/01364"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Reg Anesth Pain Med"],"accepted":{"date-parts":[[2024,6,15]]},"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/rapm-2024-105517","type":"journal-article","created":{"date-parts":[[2024,7,3]],"date-time":"2024-07-03T01:10:23Z","timestamp":1719969023000},"page":"806-814","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":4,"title":["Insights into the pathophysiology and response of persistent spinal pain syndrome type 2 to spinal cord stimulation: a human genome-wide association study"],"prefix":"10.1136","volume":"50","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1658-1466","authenticated-orcid":false,"given":"Gustavo","family":"Fabregat-Cid","sequence":"first","affiliation":[{"name":"Multidisciplinary Pain Management Department, General University Hospital Consortium of Valencia, Valencia, Spain"},{"name":"Surgery Department, University of Valencia, Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5421-802X","authenticated-orcid":false,"given":"David L","family":"Cedeno","sequence":"additional","affiliation":[{"name":"Lumbrera Research, Bloomington, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9","family":"De Andr\u00e9s","sequence":"additional","affiliation":[{"name":"Multidisciplinary Pain Management Department, General University Hospital Consortium of Valencia, Valencia, Spain"},{"name":"Surgery Department, University of Valencia, Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anushik","family":"Harutyunyan","sequence":"additional","affiliation":[{"name":"Multidisciplinary Pain Management Department, General University Hospital Consortium of Valencia, Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vicente","family":"Monsalve-Dolz","sequence":"additional","affiliation":[{"name":"Multidisciplinary Pain Management Department, General University Hospital Consortium of Valencia, Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"M\u00ednguez-Mart\u00ed","sequence":"additional","affiliation":[{"name":"Multidisciplinary Pain Management Department, General University Hospital Consortium of Valencia, Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Escriv\u00e1-Matoses","sequence":"additional","affiliation":[{"name":"Clinic University Hospital, Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Marcos","family":"Asensio-Samper","sequence":"additional","affiliation":[{"name":"Multidisciplinary Pain Management Department, General University Hospital Consortium of Valencia, Valencia, Spain"},{"name":"Surgery Department, University of Valencia, Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thiago","family":"Carnaval","sequence":"additional","affiliation":[{"name":"Neuropharmacology & Pain Group, Neuroscience Program, Bellvitge Institute for Biomedical Research, Barcelona, Spain"},{"name":"Design and Biometrics Department, Medicxact, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jes\u00fas","family":"Villoria","sequence":"additional","affiliation":[{"name":"Neuropharmacology & Pain Group, Neuroscience Program, Bellvitge Institute for Biomedical Research, Barcelona, Spain"},{"name":"Design and Biometrics Department, Medicxact, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"Rodr\u00edguez-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Genetics Laboratory; 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