Extracellular signal-regulated kinases mediate the enhancing effects of inflammatory mediators on resurgent currents in dorsal root ganglion neurons

dc.contributor.authorWu, Bin
dc.contributor.authorMcDermott, Jeff S.
dc.contributor.authorKrajewski, Jeffrey L.
dc.contributor.authorKnopp, Kelly L.
dc.contributor.authorNisenbaum, Eric S.
dc.contributor.authorCummins, Theodore R.
dc.contributor.authorTan, Zhi-Yong
dc.contributor.departmentPharmacology and Toxicology, School of Medicineen_US
dc.date.accessioned2019-08-22T16:30:50Z
dc.date.available2019-08-22T16:30:50Z
dc.date.issued2019
dc.description.abstractPreviously we reported that a group of inflammatory mediators significantly enhanced resurgent currents in dorsal root ganglion neurons. To understand the underlying intracellular signaling mechanism, we investigated the effects of inhibition of extracellular signal-regulated kinases and protein kinase C on the enhancing effects of inflammatory mediators on resurgent currents in rat dorsal root ganglion neurons. We found that the extracellular signal-regulated kinases inhibitor U0126 completely prevented the enhancing effects of the inflammatory mediators on both Tetrodotoxin-sensitive and Tetrodotoxin-resistant resurgent currents in both small and medium dorsal root ganglion neurons. U0126 substantially reduced repetitive firing in small dorsal root ganglion neurons exposed to inflammatory mediators, consistent with prevention of resurgent current amplitude increases. The protein kinase C inhibitor Bisindolylmaleimide I also showed attenuating effects on resurgent currents, although to a lesser extent compared to extracellular signal-regulated kinases inhibition. These results indicate a critical role of extracellular signal-regulated kinases signaling in modulating resurgent currents and membrane excitability in dorsal root ganglion neurons treated with inflammatory mediators. It is also suggested that targeting extracellular signal-regulated kinases-resurgent currents might be a useful strategy to reduce inflammatory pain.en_US
dc.identifier.citationWu, B., McDermott, J. S., Krajewski, J. L., Knopp, K. L., Nisenbaum, E. S., Cummins, T. R., & Tan, Z. Y. (2019). Extracellular signal-regulated kinases mediate the enhancing effects of inflammatory mediators on resurgent currents in dorsal root ganglion neurons. Molecular pain, 15, 1744806919837104. doi:10.1177/1744806919837104en_US
dc.identifier.urihttps://hdl.handle.net/1805/20508
dc.language.isoen_USen_US
dc.publisherSageen_US
dc.relation.isversionof10.1177/1744806919837104en_US
dc.relation.journalMolecular Painen_US
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 United States*
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/3.0/us*
dc.sourcePMCen_US
dc.subjectResurgent currentsen_US
dc.subjectInflammatory mediatorsen_US
dc.subjectDorsal root ganglionen_US
dc.subjectExtracellular signal-regulated kinasesen_US
dc.subjectProtein kinase Cen_US
dc.subjectTetrodotoxin-sensitiveen_US
dc.subjectTetrodotoxin-resistanten_US
dc.titleExtracellular signal-regulated kinases mediate the enhancing effects of inflammatory mediators on resurgent currents in dorsal root ganglion neuronsen_US
dc.typeArticleen_US
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