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

doi:10.1631/jzus.B1600188

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 Yu¹, Li-Hong Sun², Min Wang², Min Yan^{1

2}

Affiliations

¹ Department of Anesthesiology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.
² Jiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou 221000, China.

PMID: 27704743
PMCID: PMC5064167
DOI: 10.1631/jzus.B1600188

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.

. 2016;17(10):733-741.

doi: 10.1631/jzus.B1600188.

Authors

Li-Na Yu¹, Li-Hong Sun², Min Wang², Min Yan^{1

2}

Affiliations

¹ Department of Anesthesiology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.
² Jiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou 221000, China.

PMID: 27704743
PMCID: PMC5064167
DOI: 10.1631/jzus.B1600188

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.

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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**
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

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References

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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
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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
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[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

[2] 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

[3] 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

[4] 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

[5] 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

[6] 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

[7] 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

[8] 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

[9] 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

[10] 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

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

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

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