Qu Yu-Juan, Zhang Xiao, Fan Zhen-Zhen, Huai Juan, Teng Yong-Bo, Zhang Yang, Yue Shou-Wei
Department of Physical Medicine and Rehabilitation, Qilu Hospital of Shandong University, No. 107 Wenhuaxi Road, Jinan, Shandong 250012, China.
Department of Physical Medicine and Rehabilitation, Jinan Military General Hospital, No. 25, Shifan Road, Jinan, Shandong 250031, China.
Biomed Res Int. 2016;2016:6978923. doi: 10.1155/2016/6978923. Epub 2016 Jun 5.
The aim of this study was to investigate the relationships among TRPV4, p38, and neuropathic pain in a rat model of chronic compression of the dorsal root ganglion. Mechanical allodynia appeared after CCD surgery, enhanced via the intrathecal injection of 4α-phorbol 12,13-didecanoate (4α-PDD, an agonist of TRPV4) and anisomycin (an agonist of p38), but was suppressed by Ruthenium Red (RR, an inhibitor of TRPV4) and SB203580 (an inhibitor of p38). The protein expressions of p38 and P-p38 were upregulated by 4α-PDD and anisomycin injection but reduced by RR and SB203580. Moreover, TRPV4 was upregulated by 4α-PDD and SB203580 and downregulated by RR and anisomycin. In DRG tissues, the numbers of TRPV4- or p38-positive small neurons were significantly changed in CCD rats, increased by the agonists, and decreased by the inhibitors. The amplitudes of ectopic discharges were increased by 4α-PDD and anisomycin but decreased by RR and SB203580. Collectively, these results support the link between TRPV4 and p38 and their intermediary role for neuropathic pain in rats with chronic compression of the dorsal root ganglion.
本研究旨在探讨在背根神经节慢性压迫大鼠模型中瞬时受体电位香草酸亚型4（TRPV4）、p38与神经性疼痛之间的关系。背根神经节慢性压迫（CCD）手术后出现机械性异常性疼痛，鞘内注射4α-佛波醇12,13-十二烷酸酯（4α-PDD，TRPV4激动剂）和茴香霉素（p38激动剂）可增强该疼痛，但钌红（RR，TRPV4抑制剂）和SB203580（p38抑制剂）可抑制该疼痛。注射4α-PDD和茴香霉素可上调p38和磷酸化p38（P-p38）的蛋白表达，但RR和SB203580可使其降低。此外，4α-PDD和SB203580可上调TRPV4，而RR和茴香霉素可下调TRPV4。在背根神经节（DRG）组织中，CCD大鼠TRPV4或p38阳性小神经元数量显著改变，激动剂使其增加，抑制剂使其减少。4α-PDD和茴香霉素可增加异位放电幅度，但RR和SB203580可使其降低。总体而言，这些结果支持TRPV4与p38之间的联系及其在背根神经节慢性压迫大鼠神经性疼痛中的中介作用。
