Intervertebral foramen injection of plerixafor attenuates neuropathic pain after chronic compression of the dorsal root ganglion: Possible involvement of the down-regulation of Nav1.8 and Nav1.9.
Intervertebral foramen injection of plerixafor attenuates neuropathic pain after chronic compression of the dorsal root ganglion: Possible involvement of the down-regulation of Nav1.8 and Nav1.9.
复制标题
椎间孔注射普乐沙福可减轻背根神经节慢性受压后的神经性疼痛：可能与 Nav1.8 和 Nav1.9 的下调有关。
DOI：
10.1016/j.ejphar.2021.174322
复制
发表时间：
2021-07
影响因子：
5
通讯作者：
Wu Xiao-Zhi
中科院分区：
文献类型：
--
作者：
Yang Fei;Zou Yi-Qing;Li Min;Luo Wen-Jun;Chen Guo-Zhong;Wu Xiao-Zhi
神经病理性疼痛是一种常见的慢性疼痛，对生活质量有重要影响。然而，其病理生理机制仍不清楚，疼痛管理仍然是一个挑战。越来越多的证据表明，C-X-C趋化因子受体4（CXCR 4）在疼痛过程中起着关键作用。因此，本研究旨在研究椎间孔注射CXCR 4拮抗剂plerixafor是否能够缓解神经病理性疼痛，并探讨可能的潜在机制。慢性压迫背根神经节（CCD）是一种典型的神经病理性疼痛模型。结果表明，CCD可诱导大鼠出现多种痛行为，并使受压的背根神经节（DRG）神经元CXCR 4、Nav1.8和Nav1.9的表达显著增加。敲低CXCR 4表达可显著减轻神经病理性疼痛，椎间孔普乐沙福注射液（IVFP）可显著降低Nav1.8和Nav1.9的上调，减轻神经病理性疼痛。IVFP的镇痛持续时间至少为24 h，明显长于椎间隙注射Nav1.8阻滞剂和局麻药。因此，我们的研究提供了证据表明，IVFP可降低DRG神经元中Nav1.8和Nav1.9的表达，这可能至少部分有助于普乐沙福对CCD诱导的神经病理性疼痛的镇痛作用。结论：IVFP是治疗神经病理性疼痛的有效方法。
Neuropathic pain is a common chronic pain condition with major impact on quality of life. However, its physiopathologic mechanism remains unknown and pain management is still a challenge. Accumulating evidence indicated that C-X-C chemokine receptor type 4 (CXCR4) played a critical role in the process of pain. Thus, the present study aimed to investigate whether intervertebral foramen injection of CXCR4 antagonist, plerixafor, was able to relieve neuropathic pain and explore the possible underlying mechanism. Chronic compression of the dorsal root ganglion (CCD) was established as a typical model of neuropathic pain. The results indicated that CCD induced multiple pain-related behaviors and the expression of CXCR4, Nav1.8 and Nav1.9 was significantly increased in compressed dorsal root ganglion (DRG) neurons. Knocking down CXCR4 expression could significantly reduce neuropathic pain and intervertebral foramen plerixafor injection (IVFP) dramatically decreased the up-regulation of Nav1.8 and Nav1.9 and attenuated neuropathic pain. The analgesic duration of IVFP was maintained at least for 24 h which was much longer than intervertebral foramen injection of Nav1.8 blocker and local anesthetics. Therefore, our study provided evidence that IVFP could reduce the expression of Nav1.8 and Nav1.9 in DRG neurons which might contribute to, at least in part, the analgesic effect of plerixafor on CCD-induced neuropathic pain. It is concluded that IVFP was an effective and applicable treatment approach for neuropathic pain.