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Hypofunctional TrkA Accounts for the Absence of Pain Sensitization in the African Naked Mole-Rat

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 io...

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Autores principales: Omerbašić, Damir, Smith, Ewan St. J., Moroni, Mirko, Homfeld, Johanna, Eigenbrod, Ole, Bennett, Nigel C., Reznick, Jane, Faulkes, Chris G., Selbach, Matthias, Lewin, Gary R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5081396/
https://www.ncbi.nlm.nih.gov/pubmed/27732851
http://dx.doi.org/10.1016/j.celrep.2016.09.035
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author Omerbašić, Damir
Smith, Ewan St. J.
Moroni, Mirko
Homfeld, Johanna
Eigenbrod, Ole
Bennett, Nigel C.
Reznick, Jane
Faulkes, Chris G.
Selbach, Matthias
Lewin, Gary R.
author_facet Omerbašić, Damir
Smith, Ewan St. J.
Moroni, Mirko
Homfeld, Johanna
Eigenbrod, Ole
Bennett, Nigel C.
Reznick, Jane
Faulkes, Chris G.
Selbach, Matthias
Lewin, Gary R.
author_sort Omerbašić, Damir
collection PubMed
description 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.
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spelling pubmed-50813962016-10-28 Hypofunctional TrkA Accounts for the Absence of Pain Sensitization in the African Naked Mole-Rat Omerbašić, Damir Smith, Ewan St. J. Moroni, Mirko Homfeld, Johanna Eigenbrod, Ole Bennett, Nigel C. Reznick, Jane Faulkes, Chris G. Selbach, Matthias Lewin, Gary R. Cell Rep Article 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. Cell Press 2016-10-11 /pmc/articles/PMC5081396/ /pubmed/27732851 http://dx.doi.org/10.1016/j.celrep.2016.09.035 Text en © 2016 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Omerbašić, Damir
Smith, Ewan St. J.
Moroni, Mirko
Homfeld, Johanna
Eigenbrod, Ole
Bennett, Nigel C.
Reznick, Jane
Faulkes, Chris G.
Selbach, Matthias
Lewin, Gary R.
Hypofunctional TrkA Accounts for the Absence of Pain Sensitization in the African Naked Mole-Rat
title Hypofunctional TrkA Accounts for the Absence of Pain Sensitization in the African Naked Mole-Rat
title_full Hypofunctional TrkA Accounts for the Absence of Pain Sensitization in the African Naked Mole-Rat
title_fullStr Hypofunctional TrkA Accounts for the Absence of Pain Sensitization in the African Naked Mole-Rat
title_full_unstemmed Hypofunctional TrkA Accounts for the Absence of Pain Sensitization in the African Naked Mole-Rat
title_short Hypofunctional TrkA Accounts for the Absence of Pain Sensitization in the African Naked Mole-Rat
title_sort hypofunctional trka accounts for the absence of pain sensitization in the african naked mole-rat
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5081396/
https://www.ncbi.nlm.nih.gov/pubmed/27732851
http://dx.doi.org/10.1016/j.celrep.2016.09.035
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