• Jian Wang, Wei Xu, Yan Kong, Jiangju Huang, Zhuofeng Ding, Meiling Deng, Qulian Guo, and Wangyuan Zou.
• Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
• Neuroscience. 2019 Dec 15; 423: 869786-97.

AbstractSynaptosomal-associated protein 25 (SNAP-25) plays an important role in neuropathic pain. However, the underlying mechanism is largely unknown. Vesicular glutamate transporter 2 (VGluT2) is an isoform of vesicular glutamate transporters that controls the storage and release of glutamate. In the present study, we found the expression levels of VGluT2 correlated with the upregulation of SNAP-25 in the spinal cord of rats following chronic constriction injury (CCI)-induced neuropathic pain. Cleavage of SNAP-25 by Botulinum toxin A (BoNT/A) attenuated mechanical allodynia, downregulated the expression of VGluT2 and reduced glutamate release. Overexpression of VGluT2 abolished the antinociceptive effect of BoNT/A. Upregulation of SNAP-25 in naive rats increased VGluT2 expression and induced pain-responsive behaviors. In pheochromocytoma (PC12) cells, the expression of VGluT2 was also depended on SNAP-25 dysregulation. Moreover, we found VGluT2 was involved in SNAP-25-mediated regulation of astrocyte expression and activation of the PKA/p-CREB pathway mediated the upregulation of SNAP-25 in neuropathic pain. The findings of our study indicate that VGluT2 contributes to the effect of SNAP-25 in maintaining the development of neuropathic pain and suggests a novel mechanism underlying SNAP-25 regulation of neuropathic pain.Copyright © 2019 IBRO. Published by Elsevier Ltd. All rights reserved.

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