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

Back Pain Neuralgia Pain Management Spinal Cord Stimulation

Journal

Regional anesthesia and pain medicine
ISSN: 1532-8651
Titre abrégé: Reg Anesth Pain Med
Pays: England
ID NLM: 9804508

Informations de publication

Date de publication:
02 Jul 2024
Historique:
received: 29 03 2024
accepted: 15 06 2024
medline: 4 7 2024
pubmed: 4 7 2024
entrez: 3 7 2024
Statut: aheadofprint

Résumé

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. 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. 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. 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.

Sections du résumé

BACKGROUND 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 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 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 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.

Identifiants

pubmed: 38960591
pii: rapm-2024-105517
doi: 10.1136/rapm-2024-105517
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© American Society of Regional Anesthesia & Pain Medicine 2024. No commercial re-use. See rights and permissions. Published by BMJ.

Déclaration de conflit d'intérêts

Competing interests: RV, MD, PhD: Consultant for Medtronic.

Auteurs

Gustavo Fabregat-Cid (G)

Multidisciplinary Pain Management Department, General University Hospital Consortium of Valencia, Valencia, Spain gfabregat@gmail.com.
Surgery Department, University of Valencia, Valencia, Spain.

David L Cedeno (DL)

Lumbrera Research, Bloomington, Illinois, USA.

José De Andrés (J)

Multidisciplinary Pain Management Department, General University Hospital Consortium of Valencia, Valencia, Spain.
Surgery Department, University of Valencia, Valencia, Spain.

Anushik Harutyunyan (A)

Multidisciplinary Pain Management Department, General University Hospital Consortium of Valencia, Valencia, Spain.

Vicente Monsalve-Dolz (V)

Multidisciplinary Pain Management Department, General University Hospital Consortium of Valencia, Valencia, Spain.

Ana Mínguez-Martí (A)

Multidisciplinary Pain Management Department, General University Hospital Consortium of Valencia, Valencia, Spain.

Natalia Escrivá-Matoses (N)

Clinic University Hospital, Valencia, Spain.

Juan Marcos Asensio-Samper (JM)

Multidisciplinary Pain Management Department, General University Hospital Consortium of Valencia, Valencia, Spain.
Surgery Department, University of Valencia, Valencia, Spain.

Thiago Carnaval (T)

Neuropharmacology & Pain Group, Neuroscience Program, Bellvitge Institute for Biomedical Research, Barcelona, Spain.
Design and Biometrics Department, Medicxact, Madrid, Spain.

Jesús Villoria (J)

Neuropharmacology & Pain Group, Neuroscience Program, Bellvitge Institute for Biomedical Research, Barcelona, Spain.
Design and Biometrics Department, Medicxact, Madrid, Spain.

Raquel Rodríguez-López (R)

Genetics Laboratory; Clinical Analysis Service, General University Hospital Consortium of Valencia, Valencia, Spain.

Ricardo Vallejo (R)

Wesleyan University, Bloomington, Illinois, USA.

Classifications MeSH