Overexpression of GRK6 attenuates neuropathic pain via suppression of CXCR2 in rat dorsal root ganglion.
Overexpression of GRK6 attenuates neuropathic pain via suppression of CXCR2 in rat dorsal root ganglion.
复制标题
GRK6 的过度表达通过抑制大鼠背根神经节中的 CXCR2 减轻神经性疼痛。
DOI：
10.1177/1744806916646381
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发表时间：
2016
期刊：
影响因子：
3.3
通讯作者：
Xu GY
中科院分区：
文献类型：
--
作者：
Zhou Y;Li RJ;Li M;Liu X;Zhu HY;Ju Z;Miao X;Xu GY
G蛋白偶联酶(GRK)6是GRK家族的一员，介导激动剂诱导的G蛋白偶联受体(GPCRs)的脱敏和信号传递，从而参与包括炎症和伤害性感受在内的多种过程。最近的研究表明，趋化因子通过增加各自的GPCRs的表达在慢性疼痛中发挥重要作用。本研究旨在探讨GRK6在慢性压迫性损伤(CCI)所致神经病理性疼痛模型中的作用及其与背根神经节(DRG)底物趋化因子受体的相互作用。CCI后，大鼠背根神经节L4-L6节段GRK6表达显著下调。通过坐骨神经注射慢病毒介导的生产策略过表达GRK6可显著减轻CCI大鼠的机械痛觉异常和热痛觉过敏。GRK6的过度表达还显著逆转了支配后爪的DRG神经元的过度兴奋性，并抑制了CXCR2在CCI大鼠背根神经节中的表达增强。此外，免疫共沉淀、免疫荧光和相关分析支持GRK6和CXCR2之间的相互作用。这些结果提示，GRK6可能是神经病理性疼痛的外周机制中的关键分子，GRK6的过表达可能是通过抑制CXCR2信号通路治疗神经病理性疼痛的一种潜在策略。
G protein-coupled kinase (GRK) 6 is a member of the GRK family that mediates agonist-induced desensitization and signaling of G protein-coupled receptors (GPCRs), thus involving in a wide variety of processes including inflammation and nociception. Recent studies have indicated that chemokines play an important role in chronic pain via increased expression of respective GPCRs. This study was designed to investigate the role of GRK6 and its interaction with substrate chemokine receptors in dorsal root ganglion (DRG) in a rat model of neuropathic pain induced by chronic constriction injury (CCI). Following induction of CCI, GRK6 expression was significantly downregulated in rat DRGs at L4-L6 segments. Overexpression of GRK6 using lentiviral-mediated production strategy via sciatic nerve injection markedly attenuated mechanical allodynia and thermal hyperalgesia in CCI rats. Overexpression of GRK6 also drastically reversed the hyperexcitability of DRG neurons innervating the hind paw and suppressed the enhanced expression of CXCR2 in DRGs of CCI rats. In addition, co-immunoprecipitation, immunofluorescence, and correlation analysis supported the interaction between GRK6 and CXCR2. These results suggest that GRK6 might be a key molecular involved in peripheral mechanism of neuropathic pain and that overexpression of GRK6 might be a potential strategy for treatment for neuropathic pain through inhibition of CXCR2 signal pathway.