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CLC number: R614

On-line Access: 2016-10-02

Received: 2016-04-29

Revision Accepted: 2016-07-13

Crosschecked: 2016-09-11

Cited: 1

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Citations:  Bibtex RefMan EndNote GB/T7714

 ORCID:

Li-hong Sun

http://orcid.org/0000-0003-1726-059X

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Journal of Zhejiang University SCIENCE B 2016 Vol.17 No.10 P.733-741

http://doi.org/10.1631/jzus.B1600188


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


Author(s):  Li-na Yu, Li-hong Sun, Min Wang, Min Yan

Affiliation(s):  Department of Anesthesiology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China; more

Corresponding email(s):   zryanmin@zju.edu.cn

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


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Li-na Yu, Li-hong Sun, Min Wang, Min Yan. Research progress of the role and mechanism of extracellular signal-regulated protein kinase 5 (ERK5) pathway in pathological pain[J]. Journal of Zhejiang University Science B, 2016, 17(10): 733-741.

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publisher="Zhejiang University Press & Springer",
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T1 - Research progress of the role and mechanism of extracellular signal-regulated protein kinase 5 (ERK5) pathway in pathological pain
A1 - Li-na Yu
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A1 - Min Yan
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PB - Zhejiang University Press & Springer
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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.

ERK5信号通路在病理性疼痛中的作用及其机制的研究进展

概要:细胞外信号调节蛋白激酶5(ERK5),也称大丝裂原活化蛋白激酶1,是ERK家族(MAPK大家族的一个亚家族)的一个重要成员。ERK5在背根神经节和脊髓中均有表达。本文着重阐述ERK5相关的信号通路在病理性疼痛中的作用:ERK5/CREB通路在疼痛信号的传递和痛觉过敏的形成中起重要作用;脊髓背角中ERK5的活化主要在小角质细胞;ERK5的活化可由NMDA受体介导。同时,我们细述了在病理性疼痛中,ERK5活化与NGF-TrkA和BDNF的关联。
关键词:细胞外信号调节蛋白激酶5(ERK5);疼痛;cAMP反应原件结合蛋白;N-甲基-D-天冬氨酸受体;神经生长因子;脑源性神经营养因子

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

Reference

[1]Apfel, S.C., Wright, D.E., Wiideman, A.M., et al., 1996. Nerve growth factor regulates the expression of brain-derived neurotrophic factor mRNA in the peripheral nervous system. Mol. Cell. Neurosci., 7(2):134-142.

[2]Benemei, S., Nicoletti, P., Capone, J.G., et al., 2009. CGRP receptors in the control of pain and inflammation. Curr. Opin. Pharmacol., 9(1):9-14.

[3]Campenot, R.B., MacInnis, B.L., 2004. Retrograde transport of neurotrophins: fact and function. J. Neurobiol., 58(2):217-229.

[4]Cao, Y., Li, K., Fu, K.Y., et al., 2013. Central sensitization and MAPKs are involved in occlusal interference-induced facial pain in rats. J. Pain, 14(8):793-807.

[5]Caterina, M.J., Leffler, A., Malmberg, A.B., et al., 2000. Impaired nociception and pain sensation in mice lacking the capsaicin receptor. Science, 288(5464):306-313.

[6]Cavanaugh, J.E., 2004. Role of extracellular signal regulated kinase 5 in neuronal survival. Eur. J. Biochem., 271(11):2056-2059.

[7]Chang, L., Karin, M., 2001. Mammalian MAP kinase signalling cascades. Nature, 410(6824):37-40.

[8]Coggeshall, R.E., 2005. Fos, nociception and the dorsal horn. Prog. Neurobiol., 77(5):299-352.

[9]Coull, J.A., Beggs, S., Boudreau, D., et al., 2005. BDNF from microglia causes the shift in neuronal anion gradient underlying neuropathic pain. Nature, 438(7070):1017-1021.

[10]DeLeo, J.A., Yezierski, R.P., 2001. The role of neuroinflammation and neuroimmune activation in persistent pain. Pain, 90(1-2):1-6.

[11]Freeland, K., Liu, Y.Z., Latchman, D.S., 2000. Distinct signalling pathways mediate the cAMP response element (CRE)-dependent activation of the calcitonin gene-related peptide gene promoter by cAMP and nerve growth factor. Biochem. J., 345(2):233-238.

[12]Gao, Y.J., Ji, R.R., 2010. Chemokines, neuronal-glial interactions, and central processing of neuropathic pain. Pharmacol. Ther., 126(1):56-68.

[13]Geng, S.J., Liao, F.F., Dang, W.H., et al., 2010. Contribution of the spinal cord BDNF to the development of neuropathic pain by activation of the NR2B-containing NMDA receptors in rats with spinal nerve ligation. Exp. Neurol., 222(2):256-266.

[14]Han, J.S., Adwanikar, H., Li, Z., et al., 2010. Facilitation of synaptic transmission and pain responses by CGRP in the amygdala of normal rats. Mol. Pain, 6(1):10.

[15]Hefti, F.F., Rosenthal, A., Walicke, P.A., et al., 2006. Novel class of pain drugs based on antagonism of NGF. Trends Pharmacol. Sci., 27(2):85-91.

[16]Imbe, H., Senba, E., Kimura, A., et al., 2011. Activation of mitogen-activated protein kinase in descending pain modulatory system. J. Signal Transduct., 2011:468061.

[17]Jeong, Y.C., Pyun, K., Kwon, Y.B., 2014. Inhibition of mitogen-activated protein kinases phosphorylation plays an important role in the anti-nociceptive effect of pregabalin in zymosan-induced inflammatory pain model. Biol. Pharm. Bull., 37(10):1694-1698.

[18]Ji, R.R., Woolf, C.J., 2001. Neuronal plasticity and signal transduction in nociceptive neurons: implications for the initiation and maintenance of pathological pain. Neurobiol. Dis., 8(1):1-10.

[19]Ji, R.R., Strichartz, G., 2004. Cell signaling and the genesis of neuropathic pain. Sci. STKE, 2004(252):reE14.

[20]Ji, R.R., Baba, H., Brenner, G.J., et al., 1999. Nociceptive-specific activation of ERK in spinal neurons contributes to pain hypersensitivity. Nat. Neurosci., 2(12):1114-1119.

[21]Ju, G., Hokfelt, T., Brodin, E., et al., 1987. Primary sensory neurons of the rat showing calcitonin gene-related peptide immunoreactivity and their relation to substance P-, somatostatin-, galanin-, vasoactive intestinal polypeptide- and cholecystokinin-immunoreactive ganglion cells. Cell Tissue Res., 247(2):417-431.

[22]Kamakura, S., Moriguchi, T., Nishida, E., 1999. Activation of the protein kinase ERK5/BMK1 by receptor tyrosine kinases. Identification and characterization of a signaling pathway to the nucleus. J. Biol. Chem., 274(37):26563-26571.

[23]Kato, Y., Kravchenko, V.V., Tapping, R.I., et al., 1997. BMK1/ERK5 regulates serum-induced early gene expression through transcription factor MEF2C. EMBO J., 16(23):7054-7066.

[24]Katsura, H., Obata, K., Mizushima, T., et al., 2007. Activation of extracellular signal-regulated protein kinases 5 in primary afferent neurons contributes to heat and cold hyperalgesia after inflammation. J. Neurochem., 102(5):1614-1624.

[25]Kyriakis, J.M., Avruch, J., 2001. Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation. Physiol. Rev., 81(2):807-869.

[26]Lanigan, T.M., Russo, A.F., 1997. Binding of upstream stimulatory factor and a cell-specific activator to the calcitonin/ calcitonin gene-related peptide enhancer. J. Biol. Chem., 272(29):18316-18324.

[27]Lewin, G.R., Mendell, L.M., 1993. Nerve growth factor and nociception. Trends Neurosci., 16(9):353-359.

[28]Liu, L., Cavanaugh, J.E., Wang, Y., et al., 2003. ERK5 activation of MEF2-mediated gene expression plays a critical role in BDNF-promoted survival of developing but not mature cortical neurons. PNAS, 100(14):8532-8537.

[29]Lonze, B.E., Ginty, D.D., 2002. Function and regulation of CREB family transcription factors in the nervous system. Neuron, 35(4):605-623.

[30]Mannion, R.J., Costigan, M., Decosterd, I., et al., 1999. Neurotrophins: peripherally and centrally acting modulators of tactile stimulus-induced inflammatory pain hypersensitivity. PNAS, 96(16):9385-9390.

[31]Matsuoka, Y., Yang, J., 2012. Selective inhibition of extracellular signal-regulated kinases 1/2 blocks nerve growth factor to brain-derived neurotrophic factor signaling and suppresses the development of and reverses already established pain behavior in rats. Neuroscience, 206:224-236.

[32]McCarthy, P.W., Lawson, S.N., 1990. Cell type and conduction velocity of rat primary sensory neurons with calcitonin gene-related peptide-like immunoreactivity. Neuroscience, 34(3):623-632.

[33]Michael, G.J., Averill, S., Nitkunan, A., et al., 1997. Nerve growth factor treatment increases brain-derived neurotrophic factor selectively in TrkA-expressing dorsal root ganglion cells and in their central terminations within the spinal cord. J. Neurosci., 17(21):8476-8490.

[34]Mizushima, T., Obata, K., Katsura, H., et al., 2007. Intensity-dependent activation of extracellular signal-regulated protein kinase 5 in sensory neurons contributes to pain hypersensitivity. J. Pharmacol. Exp. Ther., 321(1):28-34.

[35]Obata, K., Noguchi, K., 2004. MAPK activation in nociceptive neurons and pain hypersensitivity. Life Sci., 74(21):2643-2653.

[36]Obata, K., Katsura, H., Mizushima, T., et al., 2007. Roles of extracellular signal-regulated protein kinases 5 in spinal microglia and primary sensory neurons for neuropathic pain. J. Neurochem., 102(5):1569-1584.

[37]Park, K.A., Fehrenbacher, J.C., Thompson, E.L., et al., 2010. Signaling pathways that mediate nerve growth factor-induced increase in expression and release of calcitonin gene-related peptide from sensory neurons. Neuroscience, 171(3):910-923.

[38]Patel, T.D., Jackman, A., Rice, F.L., et al., 2000. Development of sensory neurons in the absence of NGF/TrkA signaling in vivo. Neuron, 25(2):345-357.

[39]Perkinton, M.S., Ip, J.K., Wood, G.L., et al., 2002. Phosphatidylinositol 3-kinase is a central mediator of NMDA receptor signalling to MAP kinase (Erk1/2), Akt/PKB and CREB in striatal neurones. J. Neurochem., 80(2):239-254.

[40]Pezet, S., McMahon, S.B., 2006. Neurotrophins: mediators and modulators of pain. Annu. Rev. Neurosci., 29(1):507-538.

[41]Qi, H., Mailliet, F., Spedding, M., et al., 2009. Antidepressants reverse the attenuation of the neurotrophic MEK/MAPK cascade in frontal cortex by elevated platform stress; reversal of effects on LTP is associated with GluA1 phosphorylation. Neuropharmacology, 56(1):37-46.

[42]Radtke, C., Vogt, P.M., Devor, M., et al., 2010. Keratinocytes acting on injured afferents induce extreme neuronal hyperexcitability and chronic pain. Pain, 148(1):94-102.

[43]Raghavendra, V., Tanga, F., DeLeo, J.A., 2003. Inhibition of microglial activation attenuates the development but not existing hypersensitivity in a rat model of neuropathy. J. Pharmacol. Exp. Ther., 306(2):624-630.

[44]Ren, K., Dubner, R., 2016. Activity-triggered tetrapartite neuron-glial interactions following peripheral injury. Curr. Opin. Pharmacol., 26:16-25.

[45]Riccio, A., Pierchala, B.A., Ciarallo, C.L., et al., 1997. An NGF-TrkA-mediated retrograde signal to transcription factor CREB in sympathetic neurons. Science, 277(5329):1097-1100.

[46]Rudolph, J., Xiao, Y., Pardi, A., et al., 2015. Slow inhibition and conformation selective properties of extracellular signal-regulated kinase 1 and 2 inhibitors. Biochemistry, 54(1):22-31.

[47]Sah, D.W., Ossipo, M.H., Porreca, F., 2003. Neurotrophic factors as novel therapeutics for neuropathic pain. Nat. Rev. Drug Discov., 2(6):460-472.

[48]Schicho, R., Donnerer, J., 1999. Nerve growth factor stimulates synthesis of calcitonin gene-related peptide in dorsal root ganglion cells during sensory regeneration in capsaicin-treated rats. Neurosci. Res., 35(3):183-187.

[49]Segal, R.A., 2003. Selectivity in neurotrophin signaling: theme and variations. Annu. Rev. Neurosci., 26(1):299-330.

[50]Shadiack, A.M., Sun, Y., Zigmond, R.E., 2001. Nerve growth factor antiserum induces axotomy-like changes in neuropeptide expression in intact sympathetic and sensory neurons. J. Neurosci., 21(2):363-371.

[51]Smith, G.D., Harmar, A.J., McQueen, D.S., et al., 1992. Increase in substance P and CGRP, but not somatostatin content of innervating dorsal root ganglia in adjuvant monoarthritis in the rat. Neurosci. Lett., 137(2):257-260.

[52]Snider, W.D., McMahon, S.B., 1998. Tackling pain at the source: new ideas about nociceptors. Neuron, 20(4):629-632.

[53]Springer, J., Geppetti, P., Fischer, A., et al., 2003. Calcitonin gene-related peptide as inflammatory mediator. Pulm. Pharmacol. Ther., 16(3):121-130.

[54]Sun, J.L., Xiao, C., Lu, B., et al., 2013. CX3CL1/CX3CR1 regulates nerve injury-induced pain hypersensitivity through the ERK5 signaling pathway. J. Neurosci. Res., 91(4):545-553.

[55]Sweatt, J.D., 2001. The neuronal MAP kinase cascade: a biochemical signal integration system subserving synaptic plasticity and memory. J. Neurochem., 76(1):1-10.

[56]Sweitzer, S.M., Schubert, P., DeLeo, J.A., 2001. Propentofylline, a glial modulating agent, exhibits antiallodynic properties in a rat model of neuropathic pain. J. Pharmacol. Exp. Ther., 297(3):1210-1217.

[57]Wang, C.G., Song, S.Y., Ding, Y.L., et al., 2015. Extracellular signal-regulated kinase 5 in the cerebrospinal fluid-contacting nucleus contributes to neuropathic pain in rats. Pain Physician, 18:1073-1081.

[58]Wang, R.M., Zhang, Q.G., Zhang, G.Y., 2004. Activation of ERK5 is mediated by N-methyl-D-aspartate receptor and L-type voltage-gated calcium channel via Src involving oxidative stress after cerebral ischemia in rat hippocampus. Neurosci. Lett., 357(1):13-16.

[59]Wang, X., Tournier, C., 2006. Regulation of cellular functions by the ERK5 signalling pathway. Cell. Signal., 18(6):753-760.

[60]Watkins, L.R., Maier, S.F., 2003. Glia: a novel drug discovery target for clinical pain. Nat. Rev. Drug. Discov., 2(12):973-985.

[61]Watson, F.L., Heerssen, H.M., Moheban, D.B., et al., 1999. Rapid nuclear responses to target-derived neurotrophins require retrograde transport of ligand-receptor complex. J. Neurosci., 19(18):7889-7900.

[62]Watson, F.L., Heerssen, H.M., Bhattacharyya, A., et al., 2001. Neurotrophins use the Erk5 pathway to mediate a retrograde survival response. Nat. Neurosci., 4(10):981-988.

[63]Widmann, C., Gibson, S., Jarpe, M.B., et al., 1999. Mitogen-activated protein kinase: conservation of a three-kinase module from yeast to human. Physiol. Rev., 79(1):143-180.

[64]Wisden, W., Errington, M.L., Williams, S., et al., 1990. Differential expression of immediate early genes in the hippocampus and spinal cord. Neuron, 4(4):603-614.

[65]Woolf, C.J., Salter, M.W., 2000. Neuronal plasticity: increasing the gain in pain. Science, 288(5472):1765-1769.

[66]Wu, C., Boustany, L., Liang, H., et al., 2007. Nerve growth factor expression after plantar incision in the rat. Anesthesiology, 107(1):128-135.

[67]Xiao, C., Zhang, L., Cheng, Q.P., et al., 2008. The activation of extracellular signal-regulated protein kinase 5 in spinal cord and dorsal root ganglia contributes to inflammatory pain. Brain Res., 1215:76-86.

[68]Yang, C.C., Ornatsky, O.I., McDermott, J.C., et al., 1998. Interaction of myocyte enhancer factor 2 (MEF2) with a mitogen-activated protein kinase, ERK5/BMK1. Nucleic Acids Res., 26(20):4771-4777.

[69]Yu, S.J., Xia, C.M., Kay, J.C., et al., 2012. Activation of extracellular signal-regulated protein kinase 5 is essential for cystitis- and nerve growth factor-induced calcitonin gene-related peptide expression in sensory neurons. Mol. Pain, 8(1):48.

[70]Zhang, L., Xiao, C., Wang, J.K., et al., 2009. Activation of extracellular signal-regulated protein kinases 5 in the spinal cord contributes to the neuropathic pain behaviors induced by CCI in rats. Neurol. Res., 31(10):1037-1043.

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