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Decreased Expression and Role of GRK6 in Spinal Cord of Rats After Chronic Constriction Injury

Neurochemical Research volume 38, pages 2168–2179 (2013)Cite this article

Abstract

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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Acknowledgments

This work was supported by the National Natural Science Foundation of China (No. 21077061, No. 81172879, No. 81202368); A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).

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Affiliations

  1. Department of Anesthesiology, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, People’s Republic of China

    Yuan Zhou, Hao Wu, Yue Xu & Su Cao

  2. Department of Immunology, Medical College, Nantong University, Nantong, 226001, Jiangsu, People’s Republic of China

    Xiaodong Huang, Tao Tao, Guangfei Xu & Chun Cheng

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  1. Yuan Zhou
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  2. Xiaodong Huang
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  7. Chun Cheng
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Correspondence to Chun Cheng or Su Cao.

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Zhou, Y., Huang, X., Wu, H. et al. Decreased Expression and Role of GRK6 in Spinal Cord of Rats After Chronic Constriction Injury. Neurochem Res 38, 2168–2179 (2013). https://doi.org/10.1007/s11064-013-1125-x

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  • DOI: https://doi.org/10.1007/s11064-013-1125-x

Keywords

  • GRK6
  • Spinal cord
  • Neuropathic pain
  • Neuron
  • TNF-α