title: Genomics of the Effect of Spinal Cord Stimulation on an Animal Model of Neuropathic Pain.
abstract: BACKGROUND
  Few studies have evaluated single-gene changes modulated by spinal cord stimulation (SCS), providing a narrow understanding of molecular changes. Genomics allows for a robust analysis of holistic gene changes in response to stimulation.
  
  
  METHODS
  Rats were randomized into six groups to determine the effect of continuous SCS in uninjured and spared-nerve injury (SNI) animals. After behavioral assessment, tissues from the dorsal quadrant of the spinal cord (SC) and dorsal root ganglion (DRG) underwent full-genome microarray analyses. Weighted Gene Correlation Network Analysis (WGCNA), and Gene Ontology (GO) analysis identified similar expression patterns, molecular functions and biological processes for significant genes.
  
  
  RESULTS
  Microarray analyses reported 20,985 gene probes in SC and 19,104 in DRG. WGCNA sorted 7449 SC and 4275 DRG gene probes into 29 and 9 modules, respectively. WGCNA provided significant modules from paired comparisons of experimental groups. GO analyses reported significant biological processes influenced by injury, as well as the presence of an electric field. The genes Tlr2, Cxcl16, and Cd68 were used to further validate the microarray based on significant response to SCS in SNI animals. They were up-regulated in the SC while both Tlr2 and Cd68 were up-regulated in the DRG.
  
  
  CONCLUSIONS
  The process described provides highly significant interconnected genes and pathways responsive to injury and/or electric field in the SC and DRG. Genes in the SC respond significantly to the SCS in both injured and uninjured animals, while those in the DRG significantly responded to injury, and SCS in injured animals.
authors.affiliation: Basic Science Research, Millennium Pain Center, Bloomington, IL, USA.|School of Biological Sciences, Illinois State University, Normal, IL, USA.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Vallejo
authors.affiliation: Basic Science Research, Millennium Pain Center, Bloomington, IL, USA.|School of Biological Sciences, Illinois State University, Normal, IL, USA.
authors.forename: Dana M
authors.initials: DM
authors.lastname: Tilley
authors.affiliation: Basic Science Research, Millennium Pain Center, Bloomington, IL, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: Cedeño
authors.affiliation: Basic Science Research, Millennium Pain Center, Bloomington, IL, USA.|School of Biological Sciences, Illinois State University, Normal, IL, USA.
authors.forename: Courtney A
authors.initials: CA
authors.lastname: Kelley
authors.affiliation: Basic Science Research, Millennium Pain Center, Bloomington, IL, USA.
authors.forename: Margaret
authors.initials: M
authors.lastname: DeMaegd
authors.affiliation: Basic Science Research, Millennium Pain Center, Bloomington, IL, USA.|School of Biological Sciences, Illinois State University, Normal, IL, USA.|Medical School, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
authors.forename: Ramsin
authors.initials: R
authors.lastname: Benyamin
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics / Q000378:metabolism; D064229:Biological Ontologies; D001703:Biophysics; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D053263:Gene Regulatory Networks; D023281:Genomics; D046228:Microarray Analysis; D009437:Neuralgia / Q000378:metabolism* / Q000628:therapy*; D010147:Pain Measurement; D017288:Pain Threshold; D010812:Physical Stimulation; D051381:Rats; D013116:Spinal Cord / Q000378:metabolism; D062187:Spinal Cord Stimulation / Q000379:methods*; D013997:Time Factors; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D051195:Toll-Like Receptor 2; C539355:CD68 protein, rat; D000097382:CD68 Molecule; C495343:Tlr2 protein, rat
keywords: Animal model; chronic neuropathic pain; genomics; pain pathways; spinal cord stimulation