ERK2 alone drives inflammatory pain but cooperates with ERK1 in sensory neuron survival

Daniel E. O’Brien, Benedict J. Alter, Maiko Satomoto, Clinton D. Morgan, Steve Davidson, Sherri K. Vogt, Megan E. Norman, Graydon B. Gereau, Joseph A. Demaro, Gary E. Landreth, Judith P. Golden, Robert W. Gereau

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Extracellular signal-regulated kinases 1 and 2 (ERK1/2) are highly homologous yet distinct components of signal transduction pathways known to regulate cell survival and function. Recent evidence indicates an isoform-specific role for ERK2 in pain processing and peripheral sensitization. However, the function of ERK2 in primary sensory neurons has not been directly tested. To dissect the isoform-specific function of ERK2 in sensory neurons, we used mice with Cre-loxP-mediated deletion of ERK2 in Nav1.8+ sensory neurons that are predominantly nociceptors. We find that ERK2, unlike ERK1, is required for peripheral sensitization and cold sensation. We also demonstrate that ERK2, but not ERK1, is required to preserve epidermal innervation in a subset of peptidergic neurons. Additionally, deletion of both ERK isoforms in Nav1.8+sensory neurons leads to neuron loss not observed with deletion of either isoform alone, demonstrating functional redundancy in the maintenance of sensory neuron survival. Thus, ERK1 and ERK2 exhibit both functionally distinct and redundant roles in sensory neurons.

Original languageEnglish
Pages (from-to)9491-9507
Number of pages17
JournalJournal of Neuroscience
Volume35
Issue number25
DOIs
StatePublished - Jun 24 2015

Keywords

  • ERK
  • MAP kinase
  • MEK
  • Nociception
  • Pain
  • Sensory neuron

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    O’Brien, D. E., Alter, B. J., Satomoto, M., Morgan, C. D., Davidson, S., Vogt, S. K., Norman, M. E., Gereau, G. B., Demaro, J. A., Landreth, G. E., Golden, J. P., & Gereau, R. W. (2015). ERK2 alone drives inflammatory pain but cooperates with ERK1 in sensory neuron survival. Journal of Neuroscience, 35(25), 9491-9507. https://doi.org/10.1523/JNEUROSCI.4404-14.2015