Pharmacological interactions between calcium/calmodulin-dependent kinase II α and TRPV1 receptors in rat trigeminal sensory neurons

Theodore J. Price, Nathanial A. Jeske, Christopher M. Flores, Kenneth M. Hargreaves

Research output: Contribution to journalArticle

39 Scopus citations


Multiple lines of evidence suggest that calcium/calmodulin-dependent kinase II α (CaMKIIα) plays an important role in the spinal dorsal horn in nociceptive models of chemical, inflammatory and nerve injury. Moreover, CaMKIIα phosphorylates the vanilloid receptor type 1 (TRPV1), thereby regulating vanilloid agonist binding to the receptor. Herein, we have explored a possible interaction of CaMKIIα activity with the TRPV1 receptor in rat trigeminal ganglion (TG) neurons in vitro. Inhibition of CaMKIIα with KN-93 (5 μM) inhibited capsaicin (CAP)- and n-arachidonoyl-dopamine (NADA)-evoked calcitonin gene-related peptide (CGRP) release effectively decreasing the Emax for both compounds. This effect was not mimicked by the inactive compound KN-92 (5 μM), indicating that the effect was mediated by CaMKIIα inhibition. CAP also stimulated a significant ∼50% increase in autophosphorylation of CaMKIIα at Thr286/287. Immunocytochemistry for phospho-CaMKIIα indicated that this effect specifically occurred in TRPV1-positive TG neurons. These findings indicate that phopho-CaMKIIα is likely to play a role in presynaptic primary afferents in animal models of nociceptive hypersensitivity and provide support for CaMKIIα modulation of TRPV1 activity in sensory neurons.

Original languageEnglish (US)
Pages (from-to)94-98
Number of pages5
JournalNeuroscience Letters
Issue number2
StatePublished - Dec 2 2005



  • Calcitonin-gene related peptide
  • Calcium/calmodulin-dependent kinase II α
  • Pain
  • Trigeminal ganglion
  • Vanilloid receptor type 1

ASJC Scopus subject areas

  • Neuroscience(all)

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