Abstract

Nociceptors are a particular subtype of dorsal root ganglion (DRG) neurons that detect noxious stimuli and elicit pain. Although recent efforts have been made to reveal the molecular profile of nociceptors in normal conditions, little is known about how this profile changes in pathological conditions. In this study we exploited laser capture microdissection to specifically collect individual injured and non-injured nociceptive DRG neurons and to define their gene profiling in rat spared nerve injury (SNI) model of neuropathic pain. We found minimal transcriptional changes in non-injured neurons at 7 days after SNI. In contrast, several novel transcripts were altered in injured nociceptors, and the global signature of these LCM-captured neurons differed markedly from that the gene expression patterns found previously using whole DRG tissue following SNI. Pathway analysis of the transcriptomic profile of the injured nociceptors revealed oxidative stress as a key biological process. We validated the increase of caspase-6 (CASP6) in small-sized DRG neurons and its functional role in SNI- and paclitaxel-induced neuropathic pain. Our results demonstrate that the identification of gene regulation in a specific population of DRG neurons (e.g., nociceptors) is an effective strategy to reveal new mechanisms and therapeutic targets for neuropathic pain from different origins.

Details

Title
Gene Expression Profiling of Cutaneous Injured and Non-Injured Nociceptors in SNI Animal Model of Neuropathic Pain
Author
Temugin Berta 1 ; Perrin, Florence E 2 ; Pertin, Marie 3 ; Tonello, Raquel 4 ; Yen-Chin, Liu 5 ; Chamessian, Alexander 6 ; Kato, Ann C 7 ; Ru-Rong Ji 6 ; Decosterd, Isabelle 3 

 Pain Center, Department of anesthesiology, Lausanne University Hospital (CHUV) and Faculty of biology and medicine (FBM), University of Lausanne (UNIL), Lausanne, Switzerland; Department of Anesthesiology, Duke University Medical Center, 595 LaSalle Street, Durham, NC, USA; Pain Research Center, Department of Anesthesiology, University of Cincinnati Medical Center, Cincinnati, Ohio, USA 
 Department of Basic Neuroscience, Faculty of Medicine, Geneva, Switzerland; University of Montpellier, Montpellier, F-34095 France, INSERM, U1198, Montpellier, F-34095 France, EPHE, Paris, France 
 Pain Center, Department of anesthesiology, Lausanne University Hospital (CHUV) and Faculty of biology and medicine (FBM), University of Lausanne (UNIL), Lausanne, Switzerland; Department of Fundamental Neurosciences, Faculty of biology and medicine (FBM), University of Lausanne (UNIL), Lausanne, Switzerland 
 Pain Research Center, Department of Anesthesiology, University of Cincinnati Medical Center, Cincinnati, Ohio, USA 
 Department of Anesthesiology, College of Medicine, National Cheng Kung University, Tainan city, Taiwan 
 Department of Anesthesiology, Duke University Medical Center, 595 LaSalle Street, Durham, NC, USA 
 Department of Basic Neuroscience, Faculty of Medicine, Geneva, Switzerland 
Pages
1-11
Publication year
2017
Publication date
Aug 2017
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
1957296593
Copyright
© 2017. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.