MicroRNA-mediated GABA Aα-1 receptor subunit down-regulation in adult spinal cord following neonatal cystitis-induced chronic visceral pain in rats.
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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DOI：
10.1016/j.pain.2012.09.002
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发表时间：
2013-01
期刊：
影响因子：
7.4
通讯作者：
Banerjee B
中科院分区：
文献类型：
--
作者：
Sengupta JN;Pochiraju S;Kannampalli P;Bruckert M;Addya S;Yadav P;Miranda A;Shaker R;Banerjee B
The nociceptive transmission under pathological chronic pain conditions involves transcriptional and/or translational alteration in spinal neurotransmitters and receptors expression, and modification of neuronal function. Studies indicate the involvement of MicroRNA (miRNA)-mediated transcriptional deregulation in pathophysiology of acute and chronic pain. In the present study, we tested the hypothesis that long-term cross-organ colonic hypersensitivity in neonatally 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 (unchallenge groups) or on P30 following a zymosan re-challenge on P29 (re-challenge groups). miRNA arrays and Real-time reverse transcription polymerase chain reaction revealed significant, but differential, upregulation of mature miR-181a in the L6-S1 spinal dorsal horns from zymosan-treated rats compared with saline controls in both unchallenge and re-challenge groups. The target gene analysis demonstrated multiple complementary binding sites in miR-181a for GABAA receptor subunit GABAAα−1 gene with a miRSVR score of −1.83. Increase in miR-181a concomitantly resulted in significant downregulation of GABAAα−1 receptor subunit gene and protein expression in adult spinal cords from neonatal cystitis rats. Intrathecal administration of GABAA receptor agonist muscimol failed to attenuate viscero-motor response (VMR) to colon distension in neonatal cystitis rats, 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 GABAergic system in neonatal cystitis-induced chronic pelvic pain.
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DOI：
10.1523/jneurosci.2419-10.2010
发表时间：
2010-07-28
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
He Y;Yang C;Kirkmire CM;Wang ZJ
通讯作者：
Wang ZJ
影响因子：
2.9
作者：
Lin, C;Al-Chaer, ED
通讯作者：
Al-Chaer, ED
影响因子：
4
作者：
Costigan, M;Woolf, CJ
通讯作者：
Woolf, CJ
影响因子：
3.5
作者：
Kocerha, Jannet;Kauppinen, Sakari;Wahlestedt, Claes
通讯作者：
Wahlestedt, Claes
影响因子：
4
作者：
DeBerry, Jennifer;Randich, Alan;Ness, Timothy J.
通讯作者：
Ness, Timothy J.