Kinfe, Thomas M. ORCID: 0000-0002-4888-543X, Asif, Maria, Chakravarthy, Krishnan V., Deer, Timothy R., Kramer, Jeffery M., Yearwood, Thomas L., Hurlemann, Rene ORCID: 0000-0003-2628-565X, Hussain, Muhammad Sajid ORCID: 0000-0002-1353-8809, Motameny, Susanne, Wagle, Prerana, Nuernberg, Peter, Gravius, Sascha, Randau, Thomas ORCID: 0000-0002-5224-9639, Gravius, Nadine, Chaudhry, Shafqat R. and Muhammad, Sajjad (2019). 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. J. Transl. Med., 17. LONDON: BMC. ISSN 1479-5876

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Abstract

BackgroundIn our recent clinical trial, increased peripheral concentrations of pro-inflammatory molecular mediators were determined in complex regional pain syndrome (CRPS) patients. After 3months adjunctive unilateral, selective L4 dorsal root ganglion stimulation (L4-DRG(STIM)), 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.MethodsBlood 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 3months L4-DRG(STIM) using PANTHER pathway enrichment analysis tool.ResultsPathway 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-DRG(STIM). 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.ConclusionsIn our sub-group analysis of L4-DRG(STIM) 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

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Kinfe, Thomas M.UNSPECIFIEDorcid.org/0000-0002-4888-543XUNSPECIFIED
Asif, MariaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chakravarthy, Krishnan V.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Deer, Timothy R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kramer, Jeffery M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yearwood, Thomas L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hurlemann, ReneUNSPECIFIEDorcid.org/0000-0003-2628-565XUNSPECIFIED
Hussain, Muhammad SajidUNSPECIFIEDorcid.org/0000-0002-1353-8809UNSPECIFIED
Motameny, SusanneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wagle, PreranaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nuernberg, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gravius, SaschaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Randau, ThomasUNSPECIFIEDorcid.org/0000-0002-5224-9639UNSPECIFIED
Gravius, NadineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chaudhry, Shafqat R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Muhammad, SajjadUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-137620
DOI: 10.1186/s12967-019-1952-x
Journal or Publication Title: J. Transl. Med.
Volume: 17
Date: 2019
Publisher: BMC
Place of Publication: LONDON
ISSN: 1479-5876
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
SPINAL-CORD STIMULATION; GENE-EXPRESSION; ANIMAL-MODELMultiple languages
Medicine, Research & ExperimentalMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/13762

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