Role of SIP30 in the development and maintenance of peripheral nerve injury-induced neuropathic pain.

Role of SIP30 in the development and maintenance of peripheral nerve injury-induced neuropathic pain.
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SIP30 在周围神经损伤引起的神经性疼痛的发生和维持中的作用

DOI:
10.1016/j.pain.2009.07.011
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发表时间:
2009-11
期刊:
影响因子:
7.4
通讯作者:
Yu L
Yu L
中科院分区:
医学1区
文献类型:
--
作者:
Zhang YQ;Guo N;Peng G;Wang X;Han M;Raincrow J;Chiu CH;Coolen LM;Wenthold RJ;Zhao ZQ;Jing N;Yu L

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使用慢性压迫性损伤(CCI)神经病理性疼痛模型,我们分析了大鼠脊髓中的基因表达,并确定SIP30作为CCI后表达升高的基因。SIP30以前被证明与SNAP 25相互作用,但其功能尚不清楚。我们现在表明,在脊髓中,SIP30存在于背角板,外周伤害性输入的第一个突触,共定位与伤害性感受相关的神经肽CGRP和P物质。随着CCI手术后神经病理性疼痛的发作,SIP30 mRNA和蛋白水平增加,在同侧的脊髓,提示SIP30和神经病理性疼痛之间的潜在关联。当CCI上调SIP30被鞘内反义寡核苷酸给药抑制时,神经病理性疼痛减弱。在CCI后神经性疼痛发作期间和神经性疼痛完全建立后都观察到这种神经性疼痛减轻作用,这暗示SIP30参与神经性疼痛的发展和维持阶段。在PC12细胞中使用分泌测定,抗SIP30 siRNA减少了可用于胞吐的突触囊泡的总池,指出SIP30的潜在功能。这些结果表明SIP30在周围神经损伤诱导的神经病理性疼痛的发展和维持中的作用。
Using the chronic constriction injury (CCI) model of neuropathic pain, we profiled gene expression in the rat spinal cord, and identified SIP30 as a gene whose expression was elevated after CCI. SIP30 was previously shown to interact with SNAP25, but whose function was otherwise unknown. We now show that in the spinal cord, SIP30 was present in dorsal horn laminae where peripheral nociceptive inputs first synapse, colocalizing with nociception-related neuropeptides CGRP and substance P. With the onset of neuropathic pain after CCI surgery, SIP30 mRNA and protein levels increased in the ipsilateral side of the spinal cord, suggesting a potential association between SIP30 and neuropathic pain. When CCI-upregulated SIP30 was inhibited by intrathecal antisense oligonucleotide administration, neuropathic pain was attenuated. This neuropathic pain-reducing effect was observed both during neuropathic pain onset following CCI, and after neuropathic pain was fully established, implicating SIP30 involvement in the development and maintenance phases of neuropathic pain. Using a secretion assay in PC12 cells, anti-SIP30 siRNA decreased the total pool of synaptic vesicles available for exocytosis, pointing to a potential function for SIP30. These results suggest a role of SIP30 in the development and maintenance of peripheral nerve injury-induced neuropathic pain.
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