Files and links (1)
Published, Version of Record (VoR)CC BY V4.0, Open
Journal article
Dynamic Changes in the MicroRNA Expression Profile Reveal Multiple Regulatory Mechanisms in the Spinal Nerve Ligation Model of Neuropathic Pain
PloS one, v 6(3), pp e17670-e17670
14 Mar 2011
PMID: 21423802
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Neuropathic pain resulting from nerve lesions or dysfunction represents one of the most challenging neurological diseases to treat. A better understanding of the molecular mechanisms responsible for causing these maladaptive responses can help develop novel therapeutic strategies and biomarkers for neuropathic pain. We performed a miRNA expression profiling study of dorsal root ganglion (DRG) tissue from rats four weeks post spinal nerve ligation (SNL), a model of neuropathic pain. TaqMan low density arrays identified 63 miRNAs whose level of expression was significantly altered following SNL surgery. Of these, 59 were downregulated and the ipsilateral L4 DRG, not the injured L5 DRG, showed the most significant downregulation suggesting that miRNA changes in the uninjured afferents may underlie the development and maintenance of neuropathic pain. TargetScan was used to predict mRNA targets for these miRNAs and it was found that the transcripts with multiple predicted target sites belong to neurologically important pathways. By employing different bioinformatic approaches we identified neurite remodeling as a significantly regulated biological pathway, and some of these predictions were confirmed by siRNA knockdown for genes that regulate neurite growth in differentiated Neuro2A cells.
In vitro
validation for predicted target sites in the 3′-UTR of voltage-gated sodium channel
Scn11a
, alpha 2/delta1 subunit of voltage-dependent Ca-channel, and purinergic receptor
P2rx
ligand-gated ion channel 4 using luciferase reporter assays showed that identified miRNAs modulated gene expression significantly. Our results suggest the potential for miRNAs to play a direct role in neuropathic pain.
Metrics
Details
- Title
- Dynamic Changes in the MicroRNA Expression Profile Reveal Multiple Regulatory Mechanisms in the Spinal Nerve Ligation Model of Neuropathic Pain
- Creators
- David von Schack - PfizerMichael J. Agostino - PfizerB. Stuart Murray - PfizerYizheng Li - PfizerPadmalatha S. Reddy - PfizerJin Chen - PfizerSung E. Choe - PfizerBrian W. Strassle - PfizerChristine Li - PfizerBrian Bates - PfizerLynn Zhang - PfizerHuijuan Hu - PfizerSmita Kotnis - PfizerBrendan Bingham - PfizerWei Liu - PfizerGarth T. Whiteside - PfizerTarek A. Samad - PfizerJeffrey D. Kennedy - PfizerSeena K. Ajit - Drexel University
- Publication Details
- PloS one, v 6(3), pp e17670-e17670
- Publisher
- Public Library of Science
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000288512400018
- Scopus ID
- 2-s2.0-79952653265
- Other Identifier
- 991019167747404721
UN Sustainable Development Goals (SDGs)
This publication has contributed to the advancement of the following goals:
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Collaboration types
- Industry collaboration
- Domestic collaboration
- Web of Science research areas
- Neurosciences