Ephrin B/EphB in neuropathic pain: Role and molecular mechanisms.
Eph receptor
NMDA receptor
ephrin
nerve injury
neuropathic pain
protein kinase
Journal
Fundamental & clinical pharmacology
ISSN: 1472-8206
Titre abrégé: Fundam Clin Pharmacol
Pays: England
ID NLM: 8710411
Informations de publication
Date de publication:
03 Jul 2023
03 Jul 2023
Historique:
revised:
08
06
2023
received:
03
08
2022
accepted:
19
06
2023
medline:
4
7
2023
pubmed:
4
7
2023
entrez:
4
7
2023
Statut:
aheadofprint
Résumé
Ephrins are protein ligands that act through the tyrosine kinase receptor family, Eph receptors. The role of ephrin/Eph in the critical processes involved in the development of the nervous system, including axon guidance and cell migration, has been well documented. Moreover, studies have shown an upregulation of ephrin B1/EphB1 and ephrin B2/EphB2 in neuropathic pain of different etiology. The activation of the ephrin B/EphB system in the dorsal root ganglion and dorsal horn of the spinal cord may be essential in initiating and maintaining neuropathic pain. Accordingly, it can be proposed that the pharmacological inhibitors of EphB receptors may be potentially employed to manage the manifestations of pain. One of the primary mechanisms involved in ephrin B/EphB-mediated synaptic plasticity includes phosphorylation and activation of NMDA receptors, which may be secondary to activation of different kinases, including MAP kinases (MAPK), protein kinase C (PKC), and Src family kinases (SFK). The other molecular mechanisms may include activation of inflammatory cytokines in the spinal cord, caspase-3, calpain-1, phosphoinositide 3-kinase (PI3K), protein kinase A (PKA), and cAMP Response Element-Binding Protein (CREB). The present review discusses the role and molecular mechanisms involved in ephrin B/EphB-mediated neuropathic pain of different etiology.
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2023 Société Française de Pharmacologie et de Thérapeutique. Published by John Wiley & Sons Ltd.
Références
Kullander K, Klein R. Mechanisms and functions of Eph and ephrin signalling. Nat Rev Mol Cell Biol. 2002;3(7):475-486. doi:10.1038/nrm856
Lahaie S, Morales D, Bagci H, et al. The endosomal sorting adaptor HD-PTP is required for ephrin-B:EphB signalling in cellular collapse and spinal motor axon guidance. Sci Rep. 2019;9(1):11945. doi:10.1038/s41598-019-48421-9
Goldshmit Y, McLenachan S, Turnley A. Roles of Eph receptors and ephrins in the normal and damaged adult CNS. Brain Res Rev. 2006;52(2):327-345. doi:10.1016/j.brainresrev.2006.04.006
Pasquale EB. Eph-ephrin bidirectional signaling in physiology and disease. Cell. 2008;133(1):38-52. doi:10.1016/j.cell.2008.03.011
Henderson NT, Dalva MB. EphBs and ephrin-Bs: trans-synaptic organizers of synapse development and function. Mol Cell Neurosci. 2018;91:108-121. doi:10.1016/j.mcn.2018.07.002
Battaglia AA, Sehayek K, Grist J, McMahon SB, Gavazzi I. EphB receptors and ephrin-B ligands regulate spinal sensory connectivity and modulate pain processing. Nat Neurosci. 2003;6(4):339-340. doi:10.1038/nn1034
Yu LN, Sun LH, Wang M, et al. EphrinB-EphB signaling induces hyperalgesia through ERK5/CREB pathway in rats. Pain Physician. 2017;20(4):E563-E574. doi:10.36076/ppj.2017.E574
Kobayashi H, Kitamura T, Sekiguchi M, et al. Involvement of EphB1 receptor/EphrinB2 ligand in neuropathic pain. Spine (Phila pa 1976). 2007;32(15):1592-1598. doi:10.1097/BRS.0b013e318074d46a
Deng XT, Wu MZ, Xu N, Ma PC, Song XJ. Activation of ephrinB-EphB receptor signalling in rat spinal cord contributes to maintenance of diabetic neuropathic pain. Eur J Pain. 2017;21(2):278-288. doi:10.1002/ejp.922
Zhou XL, Zhang CJ, Wang Y, et al. EphrinB-EphB signaling regulates spinal pain processing via PKCγ. Neuroscience. 2015;307:64-72. doi:10.1016/j.neuroscience.2015.08.048
Zhou X, Zhang C, Zhang C, Peng Y, Wang Y, Xu H. MicroRNA-182-5p regulates nerve injury-induced nociceptive hypersensitivity by targeting ephrin type-b receptor 1. Anesthesiology. 2017;126(5):967-977. doi:10.1097/ALN.0000000000001588
Slack S, Battaglia A, Cibert-Goton V, Gavazzi I. EphrinB2 induces tyrosine phosphorylation of NR2B via Src-family kinases during inflammatory hyperalgesia. Neuroscience. 2008;156(1):175-183. doi:10.1016/j.neuroscience.2008.07.023
Yang M, Chen W, Zhang Y, Yang R, Wang Y, Yuan H. EphrinB/EphB signaling contributes to spinal nociceptive processing via calpain-1 and caspase-3. Mol Med Rep. 2018;18(1):268-278. doi:10.3892/mmr.2018.8996
Yu LN, Zhou XL, Yu J, et al. PI3K contributed to modulation of spinal nociceptive information related to ephrinBs/EphBs. PLoS ONE. 2012;7(8):e40930. doi:10.1371/journal.pone.0040930
Dong Y, Mao-Ying QL, Chen JW, Yang CJ, Wang YQ, Tan ZM. Involvement of EphB1 receptor/ephrinB1 ligand in bone cancer pain. Neurosci Lett. 2011;496(3):163-167. doi:10.1016/j.neulet.2011.04.008
Song XJ, Zheng JH, Cao JL, Liu WT, Song XS, Huang ZJ. EphrinB-EphB receptor signaling contributes to neuropathic pain by regulating neural excitability and spinal synaptic plasticity in rats. Pain. 2008;139(1):168-180. doi:10.1016/j.pain.2008.03.019
Ruan JP, Zhang HX, Lu XF, Liu YP, Cao JL. EphrinBs/EphBs signaling is involved in modulation of spinal nociceptive processing through a mitogen-activated protein kinases-dependent mechanism. Anesthesiology. 2010;112(5):1234-1249. doi:10.1097/ALN.0b013e3181d3e0df
Uchida H, Matsumoto M, Ueda H. Profiling of BoNT/C3-reversible gene expression induced by lysophosphatidic acid: EphrinB1 gene up-regulation underlying neuropathic hyperalgesia and allodynia. Neurochem Int. 2009;54(3-4):215-221. doi:10.1016/j.neuint.2008.11.004
Han Y, Song XS, Liu WT, Henkemeyer M, Song XJ. Targeted mutation of EphB1 receptor prevents development of neuropathic hyperalgesia and physical dependence on morphine in mice. Mol Pain. 2008;4:60. doi:10.1186/1744-8069-4-60
Bundesen LQ, Scheel TA, Bregman BS, Kromer LF. Ephrin-B2 and EphB2 regulation of astrocyte-meningeal fibroblast interactions in response to spinal cord lesions in adult rats. J Neurosci. 2003;23(21):7789-7800. doi:10.1523/JNEUROSCI.23-21-07789.2003
Zhao J, Yuan G, Cendan CM, et al. Nociceptor-expressed ephrin-B2 regulates inflammatory and neuropathic pain. Mol Pain. 2010;6:77. doi:10.1186/1744-8069-6-77
Zhou XL, Wang Y, Zhang CJ, Yu LN, Cao JL, Yan M. COX-2 is required for the modulation of spinal nociceptive information related to ephrinB/EphB signalling. Eur J Pain. 2015;19(9):1277-1287. doi:10.1002/ejp.657
Geis C, Graulich M, Wissmann A, et al. Evoked pain behavior and spinal glia activation is dependent on tumor necrosis factor receptor 1 and 2 in a mouse model of bone cancer pain. Neuroscience. 2010;169(1):463-474. doi:10.1016/j.neuroscience.2010.04.022
Zhang RX, Liu B, Li A, et al. Interleukin 1beta facilitates bone cancer pain in rats by enhancing NMDA receptor NR-1 subunit phosphorylation. Neuroscience. 2008;154(4):1533-1538. doi:10.1016/j.neuroscience.2008.04.072
Miletic G, Pankratz MT, Miletic V. Increases in the phosphorylation of cyclic AMP response element binding protein (CREB) and decreases in the content of calcineurin accompany thermal hyperalgesia following chronic constriction injury in rats. Pain. 2002;99(3):493-500. doi:10.1016/S0304-3959(02)00242-7
Ma Y, Chen J, Yu D, et al. cAMP-PKA signaling is involved in regulation of spinal HCN channels function in diabetic neuropathic pain. Neurosci Lett. 2021;750:135763. doi:10.1016/j.neulet.2021.135763
Deng M, Chen SR, Pan HL. Presynaptic NMDA receptors control nociceptive transmission at the spinal cord level in neuropathic pain. Cell Mol Life Sci. 2019;76(10):1889-1899. doi:10.1007/s00018-019-03047-y
Ji RR, Gereau RW, Malcangio M, Strichartz GR. MAP kinase and pain. Brain Res Rev. 2009;60(1):135-148. doi:10.1016/j.brainresrev.2008.12.011
Cao JL, Ruan JP, Ling DY, et al. Activation of peripheral ephrinBs/EphBs signaling induces hyperalgesia through a MAPKs-mediated mechanism in mice. Pain. 2008;139(3):617-631. doi:10.1016/j.pain.2008.06.023
Nie L, Ye WR, Chen S, Chirchiglia D, Wang M. Src family kinases in the central nervous system: their emerging role in pathophysiology of migraine and neuropathic pain. Curr Neuropharmacol. 2021;19(5):665-678. doi:10.2174/1570159X18666200814180218
Jaggi AS, Singh N. Mechanisms in cancer-chemotherapeutic drugs-induced peripheral neuropathy. Toxicology. 2012;291(1-3):1-9. doi:10.1016/j.tox.2011.10.019
Arbuckle MI, Komiyama NH, Delaney A, et al. The SH3 domain of postsynaptic density 95 mediates inflammatory pain through phosphatidylinositol-3-kinase recruitment. EMBO Rep. 2010;11(6):473-478. doi:10.1038/embor.2010.63