title: Overexpression of GRK6 attenuates neuropathic pain via suppression of CXCR2 in rat dorsal root ganglion.
abstract: 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.
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Institute of Neuroscience, Soochow University, Suzhou, P.R. China Department of Anesthesiology, Affiliated Hospital of Nantong University, Nantong, P.R. China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Institute of Neuroscience, Soochow University, Suzhou, P.R. China.
authors.forename: Rong-Ji
authors.initials: RJ
authors.lastname: Li
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Institute of Neuroscience, Soochow University, Suzhou, P.R. China.
authors.forename: Meng
authors.initials: M
authors.lastname: Li
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Institute of Neuroscience, Soochow University, Suzhou, P.R. China.
authors.forename: Xuelian
authors.initials: X
authors.lastname: Liu
authors.affiliation: Center for Translational Medicine, Affiliated Zhangjiagang Hospital of Soochow University, Zhangjiagang, P.R. China.
authors.forename: Hong-Yan
authors.initials: HY
authors.lastname: Zhu
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Institute of Neuroscience, Soochow University, Suzhou, P.R. China.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Ju
authors.affiliation: Center for Translational Medicine, Affiliated Zhangjiagang Hospital of Soochow University, Zhangjiagang, P.R. China.
authors.forename: Xiuhua
authors.initials: X
authors.lastname: Miao
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Institute of Neuroscience, Soochow University, Suzhou, P.R. China Center for Translational Medicine, Affiliated Zhangjiagang Hospital of Soochow University, Zhangjiagang, P.R. China guangyinxu@suda.edu.cn.
authors.forename: Guang-Yin
authors.initials: GY
authors.lastname: Xu
mesh_terms: D000818:Animals; D002908:Chronic Disease; D003251:Constriction, Pathologic; D015536:Down-Regulation; D054768:G-Protein-Coupled Receptor Kinases / Q000378:metabolism*; D005727:Ganglia, Spinal / Q000378:metabolism* / Q000473:pathology*; D006930:Hyperalgesia / Q000378:metabolism / Q000473:pathology; D008297:Male; D009437:Neuralgia / Q000378:metabolism* / Q000473:pathology*; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D017207:Rats, Sprague-Dawley; D023063:Receptors, Interleukin-8B / Q000378:metabolism*
chemical_list: D023063:Receptors, Interleukin-8B; D054768:G-Protein-Coupled Receptor Kinases; C089176:G-protein-coupled receptor kinase 6
keywords: CXCR2; GRK6; Neuropathic pain; dorsal root ganglion