Intrathecal Raf-1-selective siRNA attenuates sustained morphine-mediated thermal hyperalgesia.
Intrathecal Raf-1-selective siRNA attenuates sustained morphine-mediated thermal hyperalgesia.
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DOI：
10.1016/j.ejphar.2008.10.033
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发表时间：
2008-12-28
影响因子：
5
通讯作者：
Varga, Eva V.
中科院分区：
文献类型：
--
作者：
Tumati, Suneeta;Milnes, Tally Largent;Yamamura, Henry I.;Vanderah, Todd W.;Roeske, William R.;Varga, Eva V.
研究表明，长期的阿片类药物治疗会导致对疼痛(痛觉过敏)或通常无害(痛觉异常)刺激的敏感度增加。在慢性阿片类药物治疗中导致矛盾的疼痛敏感化的分子机制还不完全清楚。脊髓背角兴奋性疼痛神经递质(如降钙素基因相关肽(CGRP))的释放增加可能在吗啡介导的持续性反常疼痛中起作用。最近，我们已经证明，抑制Raf-1可以减弱吗啡诱导的体外培养的初级感觉神经元CGRP释放的增加。在本研究中，我们发现鞘内注射特定于Raf-1的siRNA可以降低脊髓中Raf-1的水平，从而减轻持续的吗啡诱导的大鼠热痛敏。
Studies have demonstrated that long-term opioid treatment leads to an increased sensitivity to painful (hyperalgesia) or normally innocuous (allodynia) stimuli. The molecular mechanisms that lead to paradoxical pain sensitization upon chronic opioid treatment are not completely understood. Enhanced excitatory pain neurotransmitter (such as calcitonin gene-related peptide (CGRP)) release in the dorsal horn of the spinal cord may play a role in sustained morphine-mediated paradoxical pain. Recently we have demonstrated that inhibition of Raf-1 attenuates sustained morphine treatment-mediated augmentation of CGRP release in vitro, in cultured primary sensory neurons. In the present study, we show that knockdown of spinal Raf-1 levels in vivo by intrathecal administration of Raf-1-specific siRNA attenuates sustained morphine-mediated thermal hyperalgesia in rats.
DOI：
10.1124/jpet.103.049643
发表时间：
2003-07-01
影响因子：
3.5
作者：
Varga, EV;Rubenzik, MK;Yamamura, HI
通讯作者：
Yamamura, HI
影响因子：
7.4
作者：
HARGREAVES, K;DUBNER, R;JORIS, J
通讯作者：
JORIS, J
影响因子：
5
作者：
Yue, Xu;Tumati, Suneeta;Varga, Eva V.
通讯作者：
Varga, Eva V.