Article

Changes in expression of sensory organ-specific microRNAs in rat dorsal root ganglia in association with mechanical hypersensitivity induced by spinal nerve ligation.

Department of Anesthesia, University of Iowa, 51 Newton Road, Iowa City, IA 52242, USA.
Neuroscience (Impact Factor: 3.33). 09/2009; 164(2):711-23. DOI: 10.1016/j.neuroscience.2009.08.033
Source: PubMed

ABSTRACT Chronic neuropathic pain caused by peripheral nerve injury is associated with global changes in gene expression in damaged neurons. To understand the molecular mechanisms underlying neuropathic pain, it is essential to elucidate how nerve injury alters gene expression and how the change contributes to the development and maintenance of chronic pain. MicroRNAs are non-protein-coding RNA molecules that regulate gene expression in a wide variety of biological processes mainly at the level of translation. This study investigated the possible involvement of microRNAs in gene regulation relevant to neuropathic pain. The analyses focused on a sensory organ-specific cluster of microRNAs that includes miR-96, -182, and -183. Quantitative real-time polymerase chain reaction (qPCR) analyses confirmed that these microRNAs were highly enriched in the dorsal root ganglion (DRG) of adult rats. Using the L5 spinal nerve ligation (SNL) model of chronic neuropathic pain, we observed a significant reduction in expression of these microRNAs in injured DRG neurons compared to controls. In situ hybridization and immunohistochemical analyses revealed that these microRNAs are expressed in both myelinated (N52 positive) and unmyelinated (IB4 positive) primary afferent neurons. They also revealed that the intracellular distributions of the microRNAs in DRG neurons were dramatically altered in animals with mechanical hypersensitivity. Whereas microRNAs were uniformly distributed within the DRG soma of non-allodynic animals, they were preferentially localized to the periphery of neurons in allodynic animals. The redistribution of microRNAs was associated with changes in the distribution of the stress granule (SG) protein, T-cell intracellular antigen 1 (TIA-1). These data demonstrate that SNL induces changes in expression levels and patterns of miR-96, -182, and -183, implying their possible contribution to chronic neuropathic pain through translational regulation of pain-relevant genes. Moreover, SGs were suggested to be assembled and associated with microRNAs after SNL, which may play a role in modification of microRNA-mediated gene regulation in DRG neurons.

0 Followers
 · 
106 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Endogenously expressed small noncoding microRNAs (miRNAs) play an important role in posttranscriptionally regulating gene expression by binding to mRNAs with complementary sequences. miRNA-mRNA interactions allow for cellular flexibility to fine-tune gene expression by controlling translation in response to a multitude of signaling events. Disease states or perturbations in cellular homeostasis can lead to aberrant miRNA expression. The discovery of stable miRNAs in circulation generated enormous interest in exploring their utility as potential noninvasive biomarkers. Additionally, selectively inhibiting or supplementing an miRNA contributing to pathogenesis is being pursued as a therapeutic strategy for a variety of disorders. Studies from rodent models of pain and patients have now implicated a role for miRNAs in mediating various aspects of pain processing. These noncoding RNAs can provide mechanistic insights into the pathways modulated and could serve as therapeutic targets. Here, we discuss the challenges associated with miRNA research and the promises ahead in this vastly unexplored avenue in pain biology. © 2015 Elsevier Inc. All rights reserved.
    Progress in molecular biology and translational science 01/2015; 131:215-49. DOI:10.1016/bs.pmbts.2014.11.015 · 3.11 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The long-lasting nociceptive transmission under various visceral pain conditions involves transcriptional and/or translational alter-ation in neurotransmitter and receptor expression as well as modification of neuronal function, morphology and synaptic connections. Although it is largely unknown how such changes in posttranscriptional expression induce visceral pain, recent evi-dence strongly suggests an important role for microRNAs (miRNAs, small non-coding RNAs) in the cellular plasticity underlying chronic visceral pain. MicroRNAs are small noncoding RNA endogenously produced in our body and act as a major regulator of gene expression by either through cleavage or translational repression of the target gene. This regulation is essential for the normal physiological function but when disturbed can result in pathological conditions. Usually one miRNA has multiple targets and target mRNAs are regulated in a combinatorial fashion by multiple miRNAs. In recent years, many studies have been per-formed to delineate the posttranscriptional regulatory role of miRNAs in different tissues under various nociceptive stimuli. In this review, we intend to discuss the recent development in miRNA research with special emphases on miRNAs and their tar-gets responsible for long term sensitization in chronic pain conditions. In addition, we review miRNAs expression and function data for different animal pain models and also the recent progress in research on miRNA-based therapeutic targets for the treatment of chronic pain.
    Journal of neurogastroenterology and motility 03/2015; 21(2):159-71. DOI:10.5056/jnm15027 · 2.70 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Chronic pain is a debilitating syndrome caused by a variety of disorders, and represents a major clinical problem because of the lack of adequate medication. In chronic pain, massive changes in gene expression are observed in a variety of cells, including neurons and glia, in the overall somatosensory system from the sensory ganglia to the higher central nervous system. The protein expressions of hundreds of genes are thought to be post-transcriptionally regulated by a single type of microRNA in a sequence-specific manner. Recently, critical roles of microRNAs in the pathophysiology of chronic pain have been emerging. Genome-wide screenings of microRNA expression changes have been reported in a variety of painful conditions, including peripheral nerve injury, inflammatory diseases, cancer and spinal cord injury. The data obtained suggest that a wide range of microRNAs change their expressions in individual pain conditions, although the pathological significance of individual microRNAs as causal mediators in distinct pain conditions remains to be revealed for a limited number of microRNAs. Insights into the roles of microRNAs in chronic pain will enhance our understanding of the pathophysiology of chronic pain and allow prompt therapeutic application of microRNA-related drugs against intractable persistent pain.
    Neurochemistry International 11/2014; DOI:10.1016/j.neuint.2014.05.010 · 2.65 Impact Factor