IL-6 induced upregulation of T-type Ca<sup>2+</sup> currents and sensitization of DRG nociceptors is attenuated by MNK inhibition
Vivek Jeevakumar, Aysha Khalid Al Sardar, Mohamed Farah, Clay M. Smithhart, Theodore J. Price, Gregory Dussor
Abstract
In this study, we show that the MNK inhibitor and anti-tumor agent eFT508 (tomivosertib) is effective in attenuating IL-6 induced sensitization of dorsal root ganglion (DRG) nociceptors. Pretreatment with eFT508 in DRG cultures from mice helps mitigate the development of hyperexcitability in response to IL-6. Furthermore, our data reveal that the upregulation of T-type voltage-gated calcium channels following IL-6 application can be blocked by eFT508, implicating the MNK-eIF4E signaling pathway in membrane trafficking of ion channels.
Topics & Concepts
SensitizationDownregulation and upregulationNociceptorChemistryNociceptionNeuroscienceBiophysicsCell biologyPsychologyBiologyBiochemistryReceptorGenePain Mechanisms and TreatmentsIon channel regulation and functionNeuroscience and Neuropharmacology Research