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Hypofunctional TrkA accounts for the absence of pain sensitization in the African naked mole-rat

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Item Type:Article
Title:Hypofunctional TrkA accounts for the absence of pain sensitization in the African naked mole-rat
Creators Name:Omerbašić, D. and Smith, E.S.J. and Moroni, M. and Homfeld, J. and Eigenbrod, O. and Bennett, N.C. and Reznick, J. and Faulkes, C.G. and Selbach, M. and Lewin, G.R.
Abstract:The naked mole-rat is a subterranean rodent lacking several pain behaviors found in humans, rats, and mice. For example, nerve growth factor (NGF), an important mediator of pain sensitization, fails to produce thermal hyperalgesia in naked mole-rats. The sensitization of capsaicin-sensitive TRPV1 ion channels is necessary for NGF-induced hyperalgesia, but naked mole-rats have fully functional TRPV1 channels. We show that exposing isolated naked mole-rat nociceptors to NGF does not sensitize TRPV1. However, the naked mole-rat NGF receptor TrkA displays a reduced ability to engage signal transduction pathways that sensitize TRPV1. Between one- and three-amino-acid substitutions in the kinase domain of the naked mole-rat TrkA are sufficient to render the receptor hypofunctional, and this is associated with the absence of heat hyperalgesia. Our data suggest that evolution has selected for a TrkA variant that abolishes a robust nociceptive behavior in this species but is still compatible with species fitness.
Keywords:Nerve Growth Factor, Hyperalgesia, Transcriptome Assembly, Receptor Kinase Signaling, Capsaicin Receptor, Electrophysiology, Sensitization, Nociceptor Development, Calcium Imagin, Animals, Mole-Rats
Source:Cell Reports
Publisher:Cell Press / Elsevier
Page Range:748-758
Date:11 October 2016
Official Publication:https://doi.org/10.1016/j.celrep.2016.09.035
PubMed:View item in PubMed

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