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Papers of the Week


Papers: 15 Aug 2020 - 21 Aug 2020


Animal Studies


2020 Aug 14


Science


369


6505

Editor's Pick

Importin α3 regulates chronic pain pathways in peripheral sensory neurons.

Authors

Marvaldi L, Panayotis N, Alber S, Dagan SY, Okladnikov N, Koppel I, Di Pizio A, Song D-A, Tzur Y, Terenzio M, Rishal I, Gordon D, Rother F, Hartmann E, Bader M, Fainzilber M
Science. 2020 Aug 14; 369(6505):842-846.
PMID: 32792398.

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.