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Acute Pain Increases Phosphorylation of DCLK-Long in the Edinger-Westphal Nucleus but not in the Hypothalamic Paraventricular Nucleus of the Rat

  • Tom P.H. Rouwette
    Correspondence
    Address reprint requests to Tom Rouwette, MSc, Department of Cellular Animal Physiology, Faculty of Science, Radboud University Nijmegen, P.O. Box 9010, 6500 GL Nijmegen, The Netherlands.
    Affiliations
    Department of Cellular Animal Physiology, Donders Institute for Brain, Cognition and Behaviour, Center for Neuroscience, Radboud University Nijmegen, Nijmegen, The Netherlands

    Department of Anesthesiology, Pain and Palliative Medicine, Radboud University Nijmegen, Medical Centre, Nijmegen, The Netherlands
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  • Tamás Kozicz
    Affiliations
    Department of Cellular Animal Physiology, Donders Institute for Brain, Cognition and Behaviour, Center for Neuroscience, Radboud University Nijmegen, Nijmegen, The Netherlands
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  • Nicola F.M. Olde Loohuis
    Affiliations
    Department of Cellular Animal Physiology, Donders Institute for Brain, Cognition and Behaviour, Center for Neuroscience, Radboud University Nijmegen, Nijmegen, The Netherlands
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  • Balázs Gaszner
    Affiliations
    Department of Cellular Animal Physiology, Donders Institute for Brain, Cognition and Behaviour, Center for Neuroscience, Radboud University Nijmegen, Nijmegen, The Netherlands

    Department of Anatomy, Pécs University, Hungary
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  • Erno Vreugdenhil
    Affiliations
    Leiden/Amsterdam Center for Drug Research, Medical Pharmacology Department, Leiden University, Leiden, The Netherlands
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  • Gert Jan Scheffer
    Affiliations
    Department of Anesthesiology, Pain and Palliative Medicine, Radboud University Nijmegen, Medical Centre, Nijmegen, The Netherlands
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  • Eric W. Roubos
    Affiliations
    Department of Cellular Animal Physiology, Donders Institute for Brain, Cognition and Behaviour, Center for Neuroscience, Radboud University Nijmegen, Nijmegen, The Netherlands
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  • Kris C. Vissers
    Affiliations
    Department of Anesthesiology, Pain and Palliative Medicine, Radboud University Nijmegen, Medical Centre, Nijmegen, The Netherlands
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  • Wim J.J.M. Scheenen
    Affiliations
    Department of Cellular Animal Physiology, Donders Institute for Brain, Cognition and Behaviour, Center for Neuroscience, Radboud University Nijmegen, Nijmegen, The Netherlands
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      Abstract

      The doublecortin-like kinase (DCLK) gene is crucially involved in neuronal plasticity and microtubule-guided retrograde transport of signaling molecules. We have explored the possibility that DCLK is involved in pain-induced signaling events in adult male Wistar rats. Our results show that both DCLK-short and DCLK-long splice variants are present in the cell body and proximal dendrites of neurons in stress-related nuclei, ie, the paraventricular nucleus of the hypothalamus (PVN) and the non-preganglionic Edinger-Westphal nucleus (npEW) in the rostroventral periaqueductal grey. We found that DCLK-long but not DCLK-short is phosphorylated in its serine/proline-rich domain. Furthermore, we demonstrate that phosphorylation of DCLK-long in the npEW is increased by acute pain, whereas DCLK-long phosphorylation in the PVN remains unaffected. This is the first report revealing that DCLK isoforms in the PVN and npEW occur in the adult mammalian brain and that pain differentially affects DCLK-long-mediated neuronal plasticity in these 2 stress-sensitive brain centers.

      Perspective

      Pain is a burden for society and the individual, and although the mechanisms underlying pain are relatively well known, its treatment remains difficult and incomplete. Pain stress can lead to diseases like chronic pain and depression. The differential DCLK-phosphorylation in stress-sensitive brain areas is a potential novel therapeutic target in pain research.

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