由P2X7-p38途径激活的小胶质细胞释放的微泡参与大鼠脊髓神经结扎诱导的神经性疼痛。
Microvesicles shed from microglia activated by the P2X7-p38 pathway are involved in neuropathic pain induced by spinal nerve ligation in rats.
作者信息
Li Jian, Li Xiangnan, Jiang Xin, Yang Mei, Yang Rui, Burnstock Geoffrey, Xiang Zhenghua, Yuan Hongbin
机构信息
Department of Anesthesiology, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai, 200003, China.
Department of Anesthesiology, The Third People's Hospital of Yancheng, Yancheng, 224001, China.
出版信息
Purinergic Signal. 2017 Mar;13(1):13-26. doi: 10.1007/s11302-016-9537-0. Epub 2016 Sep 28.
Abstract
Microglia are critical in the pathogenesis of neuropathic pain. In this study, we investigated the role of microvesicles (MVs) in neuropathic pain induced by spinal nerve ligation (SNL) in rats. First, we found that MVs shed from microglia were increased in the cerebrospinal fluid and dorsal horn of the spinal cord after SNL. Next, MVs significantly reduced paw withdrawal threshold (PWT) and paw withdrawal latency (PWL). In addition, the P2X7-p38 pathway was related to the bleb of MVs after SNL. Interleukin (IL)-1β was found to be significantly upregulated in the package of MVs, and PWT and PWL increased following inhibition with shRNA-IL-1β. Finally, the amplitude and frequency of spontaneous excitatory postsynaptic currents increased following stimulation with MVs. Our results indicate that the P2X7-p38 pathway is closely correlated with the shedding of MVs from microglia in neuropathic pain, and MVs had a significant effect on neuropathic pain by participating in the interaction between microglia and neurons.
摘要
小胶质细胞在神经性疼痛的发病机制中起关键作用。在本研究中，我们调查了微泡（MVs）在大鼠脊髓神经结扎（SNL）诱导的神经性疼痛中的作用。首先，我们发现SNL后，脑脊液和脊髓背角中从小胶质细胞脱落的MVs增加。其次，MVs显著降低了缩爪阈值（PWT）和缩爪潜伏期（PWL）。此外，P2X7-p38通路与SNL后MVs的出泡有关。发现白细胞介素（IL）-1β在MVs包裹物中显著上调，用shRNA-IL-1β抑制后PWT和PWL增加。最后，用MVs刺激后，自发性兴奋性突触后电流的幅度和频率增加。我们的结果表明，P2X7-p38通路与神经性疼痛中小胶质细胞MVs的脱落密切相关，并且MVs通过参与小胶质细胞与神经元之间的相互作用对神经性疼痛有显著影响。
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2
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Brain Behav Immun. 2016 Jul;55:82-92. doi: 10.1016/j.bbi.2015.11.007. Epub 2015 Nov 11.
3
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Pain. 2016 Jan;157(1):103-116. doi: 10.1097/j.pain.0000000000000339.
4
P2X receptors, sensory neurons and pain.P2X受体、感觉神经元与疼痛
Curr Med Chem. 2015;22(7):845-50. doi: 10.2174/0929867321666141011195351.
5
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Glia. 2014 Apr;62(4):592-607. doi: 10.1002/glia.22628. Epub 2014 Jan 28.
6
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Front Cell Neurosci. 2013 Dec 10;7:251. doi: 10.3389/fncel.2013.00251. eCollection 2013.
7
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