The association between spinal cord trauma-sensitive miRNAs and pain sensitivity, and their regulation by morphine.
The association between spinal cord trauma-sensitive miRNAs and pain sensitivity, and their regulation by morphine.
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DOI：
10.1016/j.neuint.2014.05.005
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发表时间：
2014-11
影响因子：
4.2
通讯作者：
Miranda RC
中科院分区：
文献类型：
--
作者：
Strickland ER;Woller SA;Hook MA;Grau JW;Miranda RC
疼痛敏感性增加是脊髓损伤（SCI）的常见后遗症。此外，吗啡等药物虽然对疼痛管理至关重要，但会引起促炎作用，加剧慢性疼痛症状。先前的报告表明，SCI导致在损伤部位以及损伤部位远端的脊髓节段中诱导和抑制几种microRNA（miRNAs）。我们假设吗啡会调节这些miRNAs的表达，这些SCI敏感的miRNAs的表达可能预测SCI后远端伤害性回路的适应。为了确定吗啡处理是否进一步失调SCI敏感性miRNA，在SCI后2或15天，通过qRT-PCR在假手术对照中以及在大鼠挫伤后响应于媒介物和吗啡处理来检查它们的表达。我们的数据表明，在损伤部位的miR 1，miR 124，和miR 129 -2的表达预测的伤害性反应介导的脊髓区域远侧病变部位，这表明一种分子机制的相互作用的SCI与适应功能完整的远端感觉运动回路。此外，SCI诱导的miRNA，miR 21诱导随后的吗啡给药，代表了一个替代的，迄今尚未确定的，适应不良反应吗啡暴露。与预测相反，促炎性白细胞介素-6受体（IL 6 R）的mRNA，SCI敏感性miRNA的一个确定的目标，也诱导SCI后，表明miRNA和靶基因表达之间的解离。此外，IL 6 R mRNA表达与运动功能呈负相关，表明炎症是脊髓功能下降的预测因子。总的来说，我们的数据表明，miR 21和其他SCI敏感的miRNA可能构成治疗靶点，不仅用于改善SCI后的功能恢复，而且用于减弱SCI对疼痛敏感性的影响。
Increased pain sensitivity is a common sequela to spinal cord injury (SCI). Moreover, drugs like morphine, though critical for pain management, elicit pro-inflammatory effects that exacerbate chronic pain symptoms. Previous reports showed that SCI results in the induction and suppression of several microRNAs (miRNAs), both at the site of injury, as well as in segments of the spinal cord distal to the injury site. We hypothesized that morphine would modulate the expression of these miRNAs, and that expression of these SCI-sensitive miRNAs may predict adaptation of distal nociceptive circuitry following SCI. To determine whether morphine treatment further dysregulates SCI-sensitive miRNAs, their expression was examined by qRT-PCR in sham controls and in response to vehicle and morphine treatment following contusion in rats, at either 2 or 15 days post-SCI. Our data indicated that expression of miR1, miR124, and miR129-2 at the injury site predicted the nociceptive response mediated by spinal regions distal to the lesion site, suggesting a molecular mechanism for the interaction of SCI with adaptation of functionally intact distal sensorimotor circuitry. Moreover, the SCI-induced miRNA, miR21 was induced by subsequent morphine administration, representing an alternate, and hitherto unidentified, maladaptive response to morphine exposure. Contrary to predictions, mRNA for the pro-inflammatory interleukin-6 receptor (IL6R), an identified target of SCI-sensitive miRNAs, was also induced following SCI, indicating dissociation between miRNA and target gene expression. Moreover, IL6R mRNA expression was inversely correlated with locomotor function suggesting that inflammation is a predictor of decreased spinal cord function. Collectively, our data indicate that miR21 and other SCI-sensitive miRNAs may constitute therapeutic targets, not only for improving functional recovery following SCI, but also for attenuating the effects of SCI on pain sensitivity.
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影响因子：
2.7
作者：
Hook, Michelle A.;Liu, Grace T.;Grau, James W.
通讯作者：
Grau, James W.
影响因子：
2.9
作者：
Cui, Y;Chen, Y;Chen, PX
通讯作者：
Chen, PX
DOI：
10.1161/atvbaha.111.226696
发表时间：
2011-11-01
影响因子：
8.7
作者：
Fichtlscherer, Stephan;Zeiher, Andreas M.;Dimmeler, Stefanie
通讯作者：
Dimmeler, Stefanie
创伤性脊髓损伤后的microRNA表达改变。
影响因子：
5.3
作者：
Liu, Nai-Kui;Wang, Xiao-Fei;Lu, Qing-Bo;Xu, Xiao-Ming
通讯作者：
Xu, Xiao-Ming
影响因子：
4.8
作者：
Frankel, Lisa B.;Christoffersen, Nanna R.;Lund, Anders H.
通讯作者：
Lund, Anders H.