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Importin α3 regulates chronic pain pathways in peripheral sensory neurons

Item Type:Article
Title:Importin α3 regulates chronic pain pathways in peripheral sensory neurons
Creators Name:Marvaldi, L. and Panayotis, N. and Alber, S. and Dagan, S.Y. and Okladnikov, N. and Koppel, I. and Di Pizio, A. and Song, D.A. and Tzur, Y. and Terenzio, M. and Rishal, I. and Gordon, D. and Rother, F. and Hartmann, E. and Bader, M. and Fainzilber, M.
Abstract:How is neuropathic pain regulated in peripheral sensory neurons? Importins are key regulators of nucleocytoplasmic transport. In this study, we found that importin α3 (also known as karyopherin subunit alpha 4) can control pain responsiveness in peripheral sensory neurons in mice. Importin α3 knockout or sensory neuron-specific knockdown in mice reduced responsiveness to diverse noxious stimuli and increased tolerance to neuropathic pain. Importin α3-bound c-Fos and importin α3-deficient neurons were impaired in c-Fos nuclear import. Knockdown or dominant-negative inhibition of c-Fos or c-Jun in sensory neurons reduced neuropathic pain. In silico screens identified drugs that mimic importin α3 deficiency. These drugs attenuated neuropathic pain and reduced c-Fos nuclear localization. Thus, perturbing c-Fos nuclear import by importin α3 in peripheral neurons can promote analgesia.
Keywords:Alpha Karyopherins, Benzophenones, Cell Nucleus Active Transport, Chronic Pain, Gene Expression Profiling, Gene Knockdown Techniques, Isoxazoles, Inbred C57BL Mice, Neuralgia, Proto-Oncogene Proteins c-fos, Sensory Receptor Cells, Transcription Factor AP-1, Animals, Mice
Publisher:American Association for the Advancement of Science
Page Range:842-846
Date:14 August 2020
Official Publication:https://doi.org/10.1126/science.aaz5875
PubMed:View item in PubMed

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