CaMKII controls whether touch is painful

Hongwei Yu, Bin Pan, Andy Weyer, Hsiang En Wu, Jingwei Meng, Gregory Fischer, Daniel Vilceanu, Alan R. Light, Cheryl Stucky, Frank L. Rice, Andy Hudmon, Quinn Hogan

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

The sensation of touch is initiated when fast conducting low-threshold mechanoreceptors (Aβ-LTMRs) generate impulses at their terminals in the skin. Plasticity in this system is evident in the process of adaption, in which a period of diminished sensitivity follows prior stimulation. CaMKII is an ideal candidate for mediating activity-dependent plasticity in touch because it shifts into an enhanced activation state after neuronal depolarizations and can thereby reflect past firing history. Here we show that sensory neuron CaMKII autophosphorylation encodes the level of Aβ-LTMR activity in rat models of sensory deprivation (whisker clipping, tail suspension, casting). Blockade of CaMKII signaling limits normal adaptation of action potential generation in Aβ-LTMRs in excised skin. CaMKII activity is also required for natural filtering of impulse trains as they travel through the sensory neuron T-junction in the DRG. Blockade of CaMKII selectively in presynaptic Aβ-LTMRs removes dorsal horn inhibition that otherwise prevents Aβ-LTMR input from activating nociceptive lamina I neurons. Together, these consequences of reduced CaMKII function in Aβ-LTMRs cause low-intensity mechanical stimulation to produce pain behavior. Weconclude that, without normal sensory activity to maintain adequate levels of CaMKII function, the touch pathway shifts into a pain system. In the clinical setting, sensory disuse may be a critical factor that enhances and prolongs chronic pain initiated by other conditions.

Original languageEnglish (US)
Pages (from-to)14086-14102
Number of pages17
JournalJournal of Neuroscience
Volume35
Issue number42
DOIs
StatePublished - Oct 21 2015

Keywords

  • Adaptation
  • CaMKII
  • DRG
  • Mechanosensation
  • Pain
  • Sensory neuron

ASJC Scopus subject areas

  • Neuroscience(all)

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    Yu, H., Pan, B., Weyer, A., Wu, H. E., Meng, J., Fischer, G., Vilceanu, D., Light, A. R., Stucky, C., Rice, F. L., Hudmon, A., & Hogan, Q. (2015). CaMKII controls whether touch is painful. Journal of Neuroscience, 35(42), 14086-14102. https://doi.org/10.1523/JNEUROSCI.1969-15.2015