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, Tamás Kozicz, Nicola F.M. Olde Loohuis, Balázs Gaszner, Erno Vreugdenhil, Gert Jan Scheffer, Eric W. Roubos, Kris C. Vissers, Wim J.J.M. Scheenen

Research output: Contribution to journalArticle

10 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)930-940
Number of pages11
JournalJournal of Pain
Volume11
Issue number10
DOIs
StatePublished - Oct 1 2010

Keywords

  • Non-preganglionic Edinger-Westphal nucleus
  • acute pain
  • doublecortin-like kinase
  • hypothalamic paraventricular nucleus
  • stress response

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Anesthesiology and Pain Medicine

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    Rouwette, T. P. H., Kozicz, T., Olde Loohuis, N. F. M., Gaszner, B., Vreugdenhil, E., Scheffer, G. J., Roubos, E. W., Vissers, K. C., & Scheenen, W. J. J. M. (2010). Acute pain increases phosphorylation of DCLK-long in the edinger-westphal nucleus but not in the hypothalamic paraventricular nucleus of the rat. Journal of Pain, 11(10), 930-940. https://doi.org/10.1016/j.jpain.2009.12.017