1. Importin α3 regulates chronic pain pathways in peripheral sensory neurons.
- Author
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Marvaldi L, Panayotis N, Alber S, Dagan SY, Okladnikov N, Koppel I, Di Pizio A, Song DA, Tzur Y, Terenzio M, Rishal I, Gordon D, Rother F, Hartmann E, Bader M, and Fainzilber M
- Subjects
- Active Transport, Cell Nucleus, Animals, Benzophenones pharmacology, Chronic Pain genetics, Gene Expression Profiling, Gene Knockdown Techniques, Isoxazoles pharmacology, Mice, Mice, Inbred C57BL, Neuralgia genetics, Proto-Oncogene Proteins c-fos antagonists & inhibitors, Proto-Oncogene Proteins c-fos metabolism, Transcription Factor AP-1 metabolism, alpha Karyopherins genetics, Chronic Pain physiopathology, Neuralgia physiopathology, Sensory Receptor Cells physiology, alpha Karyopherins physiology
- 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., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
- Published
- 2020
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