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

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dc.contributor.author Omerba sic, Damir
dc.contributor.author Smith, Ewan St. J.
dc.contributor.author Moroni, Mirko
dc.contributor.author Homfeld, Johanna
dc.contributor.author Eigenbrod, Ole
dc.contributor.author Bennett, Nigel Charles
dc.contributor.author Reznick, Jane
dc.contributor.author Faulkes, Christopher G.
dc.contributor.author Selbach, Matthias
dc.contributor.author Lewin, Gary R.
dc.date.accessioned 2016-11-14T11:37:51Z
dc.date.available 2016-11-14T11:37:51Z
dc.date.issued 2016-10-11
dc.description.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 molerat 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. en_ZA
dc.description.department Zoology and Entomology en_ZA
dc.description.librarian am2016 en_ZA
dc.description.sponsorship This work was supported by a European Research Council grant (grant 294678 Extremeophile Mammal) to G.R.L. E.S.J.S. acknowledges support from the Alexander von Humboldt foundation. en_ZA
dc.description.uri http://www.sherpa.ac.uk/romeo/issn/2211-1247/ en_ZA
dc.identifier.citation Omerba si c, D, Smith, EStJ, Moroni, M, Homfeld, J, Eigenbrod, O, Bennett, NC, Reznick, J, Faulkes, CG, Selbach, M & Lewin, GR 2016, 'Hypofunctional TrkA accounts for the absence of pain sensitization in the African naked mole-rat', Cell Reports, vol. 17, pp. 748-758. en_ZA
dc.identifier.issn 2211-1247 (print)
dc.identifier.issn 2211-1247 (online)
dc.identifier.other 10.1016/j.celrep.2016.09.035
dc.identifier.uri http://hdl.handle.net/2263/58050
dc.language.iso en en_ZA
dc.publisher Elsevier en_ZA
dc.rights © 2016 The Authors. This is an open access article under the CC BY-NC-ND license. en_ZA
dc.subject Humans en_ZA
dc.subject TRPV1 en_ZA
dc.subject Nerve growth factor (NGF) en_ZA
dc.subject Pain sensitization en_ZA
dc.subject Naked mole-rat (Heterocephalus glaber) en_ZA
dc.title Hypofunctional TrkA accounts for the absence of pain sensitization in the African naked mole-rat en_ZA
dc.type Article en_ZA


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