| MicroRNA-mediated GABA(Aα-1) receptor subunit down-regulation in adult spinal cord following neonatal cystitis-induced chronic visceral pain in rats. | |
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MedLine Citation:
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PMID: 23273104 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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The nociceptive transmission under pathological chronic pain conditions involves transcriptional and/or translational alteration in spinal neurotransmitters, receptor expressions, and modification of neuronal functions. Studies indicate the involvement of microRNA (miRNA) - mediated transcriptional deregulation in the pathophysiology of acute and chronic pain. In the present study, we tested the hypothesis that long-term cross-organ colonic hypersensitivity in neonatal zymosan-induced cystitis is due to miRNA-mediated posttranscriptional suppression of the developing spinal GABAergic system. Cystitis was produced by intravesicular injection of zymosan (1% in saline) into the bladder during postnatal (P) days P14 through P16 and spinal dorsal horns (L6-S1) were collected either on P60 (unchallenged groups) or on P30 after a zymosan re-challenge on P29 (re-challenged groups). miRNA arrays and real-time reverse transcription-polymerase chain reaction (RT-PCR) revealed significant, but differential, up-regulation of mature miR-181a in the L6-S1 spinal dorsal horns from zymosan-treated rats compared with saline-treated controls in both the unchallenged and re-challenged groups. The target gene analysis demonstrated multiple complementary binding sites in miR-181a for GABA(A) receptor subunit GABA(Aα-1) gene with a miRSVR score of -1.83. An increase in miR-181a concomitantly resulted in significant down-regulation of GABA(Aα-1) receptor subunit gene and protein expression in adult spinal cords from rats with neonatal cystitis. Intrathecal administration of the GABA(A) receptor agonist muscimol failed to attenuate the viscero-motor response (VMR) to colon distension in rats with neonatal cystitis, whereas in adult zymosan-treated rats the drug produced significant decrease in VMR. These results support an integral role for miRNA-mediated transcriptional deregulation of the GABAergic system in neonatal cystitis-induced chronic pelvic pain. |
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Authors:
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Jyoti N Sengupta; Soumiya Pochiraju; Pradeep Kannampalli; Mitchell Bruckert; Sankar Addya; Priyanka Yadav; Adrian Miranda; Reza Shaker; Banani Banerjee |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Pain Volume: 154 ISSN: 1872-6623 ISO Abbreviation: Pain Publication Date: 2013 Jan |
Date Detail:
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Created Date: 2012-12-31 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7508686 Medline TA: Pain Country: Netherlands |
Other Details:
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Languages: eng Pagination: 59-70 Citation Subset: IM |
Copyright Information:
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Copyright © 2012 International Association for the Study of Pain. All rights reserved. |
Affiliation:
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Division of Gastroenterology and Hepatology, Medical College of Wisconsin, Milwaukee, WI 53226, USA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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