Importin α3 regulates chronic pain pathways in peripheral sensory neurons

doi:10.1126/science.aaz5875

GSTDTAP > 气候变化

DOI	10.1126/science.aaz5875
	Importin α3 regulates chronic pain pathways in peripheral sensory neurons
	Letizia Marvaldi; Nicolas Panayotis; Stefanie Alber; Shachar Y. Dagan; Nataliya Okladnikov; Indrek Koppel; Agostina Di Pizio; Didi-Andreas Song; Yarden Tzur; Marco Terenzio; Ida Rishal; Dalia Gordon; Franziska Rother; Enno Hartmann; Michael Bader; Mike Fainzilber
	2020-08-14
发表期刊	Science
出版年	2020
英文摘要	Chronic neuropathic pain is debilitating and difficult to treat. Marvaldi et al. now show that chronic pain is regulated by a specific nuclear import factor in peripheral sensory neurons (see the Perspective by Yousuf and Price). Importin α3 is required for nuclear import of the transcription factor c-Fos in sensory neurons, and perturbation of this pathway ameliorates sustained neuropathic pain in mice. Candidate drugs were identified that mimic this pathway and alleviate neuropathic pain in mouse models. Identification of a nuclear transport factor that regulates pain mechanisms offers opportunities for future analgesic development. Science , this issue p. [842][1]; see also p. [774][2] 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. [1]: /lookup/doi/10.1126/science.aaz5875 [2]: /lookup/doi/10.1126/science.abd4196
领域	气候变化 ; 资源环境
URL	查看原文
引用统计
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/288092
专题	气候变化资源环境科学
推荐引用方式 GB/T 7714	Letizia Marvaldi,Nicolas Panayotis,Stefanie Alber,et al. Importin α3 regulates chronic pain pathways in peripheral sensory neurons[J]. Science,2020.
APA	Letizia Marvaldi.,Nicolas Panayotis.,Stefanie Alber.,Shachar Y. Dagan.,Nataliya Okladnikov.,...&Mike Fainzilber.(2020).Importin α3 regulates chronic pain pathways in peripheral sensory neurons.Science.
MLA	Letizia Marvaldi,et al."Importin α3 regulates chronic pain pathways in peripheral sensory neurons".Science (2020).