Decreased Expression and Role of GRK6 in Spinal Cord of Rats After Chronic Constriction Injury
Decreased Expression and Role of GRK6 in Spinal Cord of Rats After Chronic Constriction Injury
复制标题
慢性缩窄性损伤后大鼠脊髓中 GRK6 的表达下降和作用
DOI：
10.1007/s11064-013-1125-x
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发表时间：
2013-08
影响因子：
4.4
通讯作者：
Cao, Su
中科院分区：
文献类型：
--
作者：
Tao, Tao;Xu, Guangfei;Cheng, Chun;Cao, Su
神经损伤和炎症都可以通过产生促炎细胞因子诱导神经病理性疼痛。在此过程中，G蛋白偶联受体（GPCRs）参与了痛觉信号的传递。GPCR激酶（GRK）6是GRK家族的成员，其调节激动剂诱导的GPCR的脱敏和信号传导。然而，其在神经病理性疼痛中的表达和功能尚未见报道。本研究采用成年雄性大鼠慢性压迫性损伤（CCI）模型，研究脊髓GRK 6表达的动态变化。GRK 6主要表达于腰段脊髓背角神经元的浅层，其表达在CCI诱导后双侧减少。GRK 6的变化主要在脊髓背角的IB 4和P底物阳性区。脊髓鞘内注射GRK 6可减轻CCI引起的疼痛反应。脊髓组织TNF-α水平呈GRK 6阴性表达。并通过鞘内注射抗体中和TNF-α，上调GRK 6表达，减轻CCI模型的机械性异常性疼痛和热痛敏。上述结果提示，细胞因子诱导神经元GRK 6表达下调可能是神经病理性疼痛中神经元信号传导增强的一个潜在机制。
Nerve injury and inflammation can both induce neuropathic pain via the production of pro-inflammatory cytokines. In the process, G protein-coupled receptors (GPCRs) were involved in pain signal transduction. GPCR kinase (GRK) 6 is a member of the GRK family that regulates agonist-induced desensitization and signaling of GPCRs. However, its expression and function in neuropathic pain have not been reported. In this study, we performed a chronic constriction injury (CCI) model in adult male rats and investigated the dynamic change of GRK6 expression in spinal cord. GRK6 was predominantly expressed in the superficial layers of the lumbar spinal cord dorsal horn neurons and its expression was decreased bilaterally following induction of CCI. The changes of GRK6 were mainly in IB4 and P substrate positive areas in spinal cord dorsal horn. And over-expression of GRK6 in spinal cord by lentivirus intrathecal injection attenuated the pain response induced by CCI. In addition, the level of TNF-α underwent the negative pattern of GRK6 in spinal cord. And neutralized TNF-α by antibody intrathecal injection up-regulated GRK6 expression and attenuated the mechanical allodynia and heat hyperalgesia in CCI model. All the data indicated that down-regulation of neuronal GRK6 expression induced by cytokine may be a potential mechanism that contributes to increasing neuronal signaling in neuropathic pain.
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影响因子：
2.9
作者：
DeLeo, JA;Colburn, RW;Rickman, AJ
通讯作者：
Rickman, AJ
影响因子：
7.4
作者：
Zhang L;Berta T;Xu ZZ;Liu T;Park JY;Ji RR
通讯作者：
Ji RR
DOI：
--
发表时间：
1997
期刊：
Receptors & channels
影响因子：
--
作者：
Jie Zhang;Stephen S. G. Ferguson;L. Barak;M. J. Aber;Bruno Giros;R. J. Lefkowitz;M. G. Caron
通讯作者：
Jie Zhang;Stephen S. G. Ferguson;L. Barak;M. J. Aber;Bruno Giros;R. J. Lefkowitz;M. G. Caron
影响因子：
2.7
作者：
P. Honore;C. Wade;C. Zhong;R. Harris;C. Wu;T. Ghayur;Y. Iwakura;M. Decker;C. Faltynek;J. Sullivan;M. Jarvis
通讯作者：
P. Honore;C. Wade;C. Zhong;R. Harris;C. Wu;T. Ghayur;Y. Iwakura;M. Decker;C. Faltynek;J. Sullivan;M. Jarvis
影响因子：
4.2
作者：
G. Whiteside;R. Munglani
通讯作者：
G. Whiteside;R. Munglani