Unilateral L4-dorsal root ganglion stimulation evokes pain relief in chronic neuropathic postsurgical knee pain and changes of inflammatory markers: part II whole transcriptome profiling

Journal of Translational Medicine

Peter Nürnberg¹  Muhammad Sajid Hussain¹  Maria Asif¹  Susanne Motameny¹  Prerana Wagle²  Krishnan V. Chakravarthy³  Sajjad Muhammad⁴  Rene Hurlemann⁵  Thomas M. Kinfe⁵  Shafqat R. Chaudhry⁶  Thomas L. Yearwood⁷  Timothy R. Deer⁸  Thomas Randau⁹  Nadine Gravius⁹  Sascha Gravius⁹  Jeffery M. Kramer^1,10 

[1] Cologne Center for Genomics (CCG), University of Cologne;Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne;Department of Anesthesiology and Pain Medicine, University of California;Department of Neurosurgery, University of Helsinki and Helsinki University Hospital;Department of Psychiatry, Rheinische Friedrich-Wilhelms University;Dept. of Basic Medical Sciences Shifa College of Pharmaceutical Sciences, Shifa Tameer-e-Millat University;Neuromodulation Specialists LLC;The Spine and Nerve Center of the Virginias;University Hospital Bonn, Rheinische Friedrich-Wilhelms University;Volta Research;

关键词: Dorsal root ganglion stimulation;    Chronic neuropathic pain;    Gene expression;    Transcriptome;   

DOI  :  10.1186/s12967-019-1952-x

来源: DOAJ

【 摘 要 】

Abstract Background In our recent clinical trial, increased peripheral concentrations of pro-inflammatory molecular mediators were determined in complex regional pain syndrome (CRPS) patients. After 3 months adjunctive unilateral, selective L4 dorsal root ganglion stimulation (L4-DRGSTIM), significantly decreased serum IL-10 and increased saliva oxytocin levels were assessed along with an improved pain and functional state. The current study extended molecular profiling towards gene expression analysis of genes known to be involved in the gonadotropin releasing hormone receptor and neuroinflammatory (cytokines/chemokines) signaling pathways. Methods Blood samples were collected from 12 CRPS patients for whole-transcriptome profiling in order to assay 18,845 inflammation-associated genes from frozen blood at baseline and after 3 months L4-DRGSTIM using PANTHER™ pathway enrichment analysis tool. Results Pathway enrichment analyses tools (GOrilla™ and PANTHER™) showed predominant involvement of inflammation mediated by chemokines/cytokines and gonadotropin releasing hormone receptor pathways. Further, screening of differentially regulated genes showed changes in innate immune response related genes. Transcriptomic analysis showed that 21 genes (predominantly immunoinflammatory) were significantly changed after L4-DRGSTIM. Seven genes including TLR1, FFAR2, IL1RAP, ILRN, C5, PKB and IL18 were down regulated and fourteen genes including CXCL2, CCL11, IL36G, CRP, SCGB1A1, IL-17F, TNFRSF4, PLA2G2A, CREB3L3, ADAMTS12, IL1F10, NOX1, CHIA and BDKRB1 were upregulated. Conclusions In our sub-group analysis of L4-DRGSTIM treated CRPS patients, we found either upregulated or downregulated genes involved in immunoinflammatory circuits relevant for the pathophysiology of CRPS indicating a possible relation. However, large biobank-based approaches are recommended to establish genetic phenotyping as a quantitative outcome measure in CRPS patients. Trial registration The study protocol was registered at the 15.11.2016 on German Register for Clinical Trials (DRKS ID 00011267). https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00011267

【 授权许可】

Unknown