Cell reports (Cambridge), 2016-10, Vol.17 (3), p.748-758
2016
Details
- Autor(en) / Beteiligte
- Titel
- Hypofunctional TrkA Accounts for the Absence of Pain Sensitization in the African Naked Mole-Rat
- Ist Teil von
- Cell reports (Cambridge), 2016-10, Vol.17 (3), p.748-758
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2016
- Link zum Volltext
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- 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. [Display omitted] •TRPV1 ion channels in naked mole-rat nociceptors are not sensitized by NGF•Naked mole-rat TRPV1 channels are sensitized by NGF in mouse nociceptors•NGF activation of naked mole-rat TrkA receptors does not sensitize TRPV1•One to three amino acids in the naked mole-rat TrkA receptors may render it hypofunctional Omerbašić et al. show that absent pain sensitization in naked mole-rats is associated with hypofunctional TrkA signaling. NGF stimulation of TrkA normally sensitizes TRPV1 channels, but not in naked mole-rat sensory neurons. The naked mole-rat TrkA kinase domain was shown to contain amino acid variants that attenuate TRPV1-dependent pain sensitization.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2211-1247eISSN: 2211-1247DOI: 10.1016/j.celrep.2016.09.035Titel-ID: cdi_doaj_primary_oai_doaj_org_article_5a53381f1a6e4a2e9ea0fc3b22fdab77
- Format
- –
- Schlagworte
- Animals, calcium imaging, capsaicin receptor, electrophysiology, Ganglia, Spinal - metabolism, HEK293 Cells, Humans, hyperalgesia, Ion Channel Gating - drug effects, Mole Rats, nerve growth factor, Nerve Growth Factor - pharmacology, Neurons - drug effects, Neurons - metabolism, nociceptor development, Nociceptors - metabolism, Pain - metabolism, Pain - pathology, Pain - physiopathology, Protein Domains, Proteomics, receptor kinase signaling, Receptor, trkA - chemistry, Receptor, trkA - metabolism, sensitization, transcriptome assembly, TRPV Cation Channels - metabolism