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Protein Kinase C γ Contributes to Central Sensitization in a Rat Model of Chronic Migraine

Journal of Molecular Neuroscience volume 63, pages 131–141 (2017)Cite this article

Abstract

Protein kinase C γ (PKCγ) is a critical regulator of central sensitization and is widely recognized to be involved in the pathogenesis of chronic migraine (CM). However, the function of PKCγ in CM remains unknown. This study investigated the role of PKCγ on pathogenesis of CM. We repeated infusions of inflammatory soup (IS) on the intact dura of conscious rats to model recurrent trigeminovascular or dural nociceptor activation assumed to occur in patients with CM. The von Frey test was then used to detect changes in pain threshold. QT-PCR, western blotting, and double immunofluorescence staining were performed to detect the expression and location of PKCγ in the trigeminal nucleus caudalis (TNC) and the expressions of calcitonin gene-related peptide (CGRP), c-Fos, and phosphorylation level of GluR1 subunit at serine 831. Chelerythrine chloride (CHE) and phorbol 12-myristate 13-acetate (PMA) were administrated to investigate the role of PKCγ in central sensitization. We found that repeated infusions of IS induced mechanical allodynia. PKCγ was significantly increased in TNC after CM. Furthermore, inhibition of PKCγ by CHE relieved allodynia and reduced the expression of CGRP and c-Fos. Activation of PKCγ by PMA aggravated allodynia and increased the expression of CGRP and c-Fos. In addition, inhibition of PKCγ reduced the phosphorylation level of GluR1; in contrast, activation of PKCγ increased the phosphorylation level of GluR1. These results suggest PKCγ-induced GluR1 phosphorylation might participate in central sensitization in a rat model of CM. We suggest that PKCγ is a potential therapeutic target for CM.

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Affiliations

  1. Laboratory Research Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China

    Baixue Wu, Sha Wang, Guangcheng Qin, Jingmei Xie & Lixue Chen

  2. Chongqing Key Laboratory of Neurology, Chongqing, China

    Ge Tan & Jiying Zhou

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  1. Baixue Wu
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  2. Sha Wang
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  4. Jingmei Xie
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  7. Lixue Chen
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Correspondence to Lixue Chen.

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Wu, B., Wang, S., Qin, G. et al. Protein Kinase C γ Contributes to Central Sensitization in a Rat Model of Chronic Migraine. J Mol Neurosci 63, 131–141 (2017). https://doi.org/10.1007/s12031-017-0960-7

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  • DOI: https://doi.org/10.1007/s12031-017-0960-7

Keywords

  • PKC γ
  • Central sensitization
  • Chronic migraine
  • Trigeminal nucleus caudalis