Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2016;17(10):733-741.
doi: 10.1631/jzus.B1600188.

Research progress of the role and mechanism of extracellular signal-regulated protein kinase 5 (ERK5) pathway in pathological pain

Li-Na Yu  1 , Li-Hong Sun  2 , Min Wang  2 , Min Yan  1   2
Affiliations
Review

Research progress of the role and mechanism of extracellular signal-regulated protein kinase 5 (ERK5) pathway in pathological pain

Li-Na Yu et al. J Zhejiang Univ Sci B. 2016.

Abstract

Extracellular signal-regulated protein kinase 5 (ERK5), also known as big mitogen-activated protein kinase 1 (MAPK1), is an important member of ERK family, which is a subfamily of the large MAPK family. ERK5 is expressed in many tissues, including the dorsal root ganglion (DRG) neurons and the spinal cord. In this review, we focus on elaborating ERK5-associated pathway in pathological pain, in which the ERK5/CREB (cyclic adenosine monophosphate (cAMP)-response element-binding protein) pathway plays a crucial role in the transduction of pain signal and contributes to pain hypersensitivity. ERK5 activation in the spinal dorsal horn occurs mainly in microglia. The activation of ERK5 can be mediated by N-methyl-D-aspartate (NMDA) receptors. We also elaborate the relationship between ERK5 activation and nerve growth factor-tyrosine kinase A (NGF-TrkA), and the connection between ERK5 activation and brain-derived neurotrophic factor (BDNF) in pathological pain in detail.

Keywords: Brain-derived neurotrophic factor (BDNF); Cyclic adenosine monophosphate (cAMP)-response element-binding protein (CREB); Extracellular signal-regulated protein kinase 5 (ERK5); N-methyl-D-aspartate (NMDA); Nerve growth factor (NGF); Pain.

PubMed Disclaimer

Conflict of interest statement

Compliance with ethics guidelines: Li-na YU, Li-hong SUN, Min WANG, and Min YAN declare that they have no conflict of interest. This article does not contain any studies with human or animal subjects performed by any of the authors.

Figures

Fig. 1
Fig. 1
Upstream and downstream mechanisms of the ERK5 signaling cascade in DRG neurons Dashed lines indicate the need for further examination of possible signaling or the mechanism, which is complicated and abbreviated in this text. See text for details
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Apfel SC, Wright DE, Wiideman AM, et al. Nerve growth factor regulates the expression of brain-derived neurotrophic factor mRNA in the peripheral nervous system. Mol Cell Neurosci. 1996;7(2):134–142. (Available from: http://dx.doi.org/10.1006/mcne.1996.0010) - DOI - PubMed
    1. Benemei S, Nicoletti P, Capone JG, et al. CGRP receptors in the control of pain and inflammation. Curr Opin Pharmacol. 2009;9(1):9–14. (Available from: http://dx.doi.org/10.1016/j.coph.2008.12.007) - DOI - PubMed
    1. Campenot RB, MacInnis BL. Retrograde transport of neurotrophins: fact and function. J Neurobiol. 2004;58(2):217–229. (Available from: http://dx.doi.org/10.1002/neu.10322) - DOI - PubMed
    1. Cao Y, Li K, Fu KY, et al. Central sensitization and MAPKs are involved in occlusal interference-induced facial pain in rats. J Pain. 2013;14(8):793–807. (Available from: http://dx.doi.org/10.1016/j.jpain.2013.02.005) - DOI - PMC - PubMed
    1. Caterina MJ, Leffler A, Malmberg AB, et al. Impaired nociception and pain sensation in mice lacking the capsaicin receptor. Science. 2000;288(5464):306–313. (Available from: http://dx.doi.org/10.1126/science.288.5464.306) - DOI - PubMed

MeSH terms

Substances