Triptans attenuate capsaicin-induced CREB phosphorylation within the trigeminal nucleus caudalis: a mechanism to prevent central sensitization?

Dimos D. Mitsikostas*, Yolande E. Knight, Michele Lasalandra, Nikolaos Kavantzas, Peter Goadsby

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)

Abstract

The c-AMP-responsive element binding protein (CREB) and its phosphorylated product (P-CREB) are nuclear proteins expressed after stimulation of pain-producing areas of the spinal cord. There is evidence indicating that central sensitization within dorsal horn neurons is dependent on P-CREB transcriptional regulation. The objectives of the study were to investigate the expression of P-CREB in cells in rat trigeminal nucleus caudalis after noxious stimulation and to determine whether pre-treatment with specific anti-migraine agents modulate this expression. CREB and P-CREB labelling was investigated within the trigeminal caudalis by immunohistochemistry after capsaicin stimulation. Subsequently, the effect of i.v. pre-treatment with either sumatriptan (n = 5), or naratriptan (n = 7) on P-CREB expression was studied. Five animals pre-treated with i.v. normal saline were served as controls. CREB and P-CREB labelling was robust in all animal groups within Sp5C. Both naratriptan and sumatriptan decreased P-CREB expression (p = 0.0003 and 0.0013) within the Sp5C. Triptans attenuate activation of CREB within the central parts of the trigeminal system, thereby leading to potential inhibition of central sensitization. P-CREB may serve as a new marker for post-synaptic neuronal activation within Sp5C in animal models relevant to migraine.

Original languageEnglish
Pages (from-to)411-417
Number of pages7
JournalJournal of Headache and Pain
Volume12
Issue number4
DOIs
Publication statusPublished - Aug 2011

Keywords

  • CREB
  • Sumatriptan
  • Naratriptan
  • Capsaicin
  • Migraine
  • Sensitization
  • C-FOS EXPRESSION
  • GENE-RELATED PEPTIDE
  • SUPERIOR SAGITTAL SINUS
  • BINDING PROTEIN-PHOSPHORYLATION
  • CERVICAL-SPINAL-CORD
  • DORSAL-HORN
  • TRIGEMINOCERVICAL COMPLEX
  • ANIMAL-MODELS
  • CYCLIC-AMP
  • KINASE-A

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