Pluto Bioinformatics

GSE137515: Genetic screen for neuropathic pain study in importin alpha3 knock out mice

Bulk RNA sequencing

Here we show that importin alpha () 3 (KPNA4) controls pain responsiveness in peripheral sensory neurons. An importin 3 knockout mouse showed reduced responsiveness to noxious heat or chemical pain, as well as greater tolerance to neuropathic pain. Similar findings were obtained upon acute knockdown of importin 3 in peripheral sensory neurons. Transcriptome analyses and immunohistochemistry indicated that importin 3 deficient neurons were impaired in nuclear import of c-Fos. Forty days after spared nerve injury acute down-regulation of importin 3, c-FOS, Jun and the dominat negative AAV9 viruses rescue the neuropathic pain phenotype. In silico screens identified importin 3 deficiency mimicking drug leads that attenuated neuropathic pain and reduced c-Fos nuclear localization. Hence, perturbing c-Fos nuclear import by importin 3 can provide analgesia at peripheral loci in the nervous system SOURCE: Mike Fainzilber (mike.fainzilber@weizmann.ac.il) - Weizmann Institute of Science