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Papers of the Week


Papers: 30 Jul 2022 - 5 Aug 2022


Animal Studies


2022 Jul 29


Pain

ARMS/Kidins220 regulates nociception by controlling BDNF secretion.

Authors

Sánchez-Sánchez J, Vicente-García C, Cañada-García D, Martín-Zanca D, Arévalo JC
Pain. 2022 Jul 29.
PMID: 35916735.

Abstract

Pain is an alarm mechanism to prevent body damage in response to noxious stimuli. The NGF/TrkA axis plays an essential role as pain mediator and several clinical trials using antibodies against NGF have been yielded promising results, but side effects have precluded their clinical approval. A better understanding of the mechanism of NGF/TrkA-mediated nociception is needed. Here, we find that ARMS/Kidins220, a scaffold protein for Trk receptors, is a modulator of nociception. Male mice, with ARMS/Kidins220 reduction exclusively in TrkA-expressing cells, displayed hyperalgesia to heat, inflammatory and capsaicin stimuli, but not to cold or mechanical stimuli. Simultaneous deletion of BDNF reversed the effects of ARMS/Kidins220 knock-down alone. Mechanistically, ARMS/Kidins220 levels are reduced in vitro and in vivo in response to capsaicin through calpains, and this reduction leads to enhanced regulated BDNF secretion from DRGs. Altogether, these data indicate that ARMS/Kidins220 protein levels have a role as a pain modulator in the NGF/TrkA axis regulating BDNF secretion.