2. Academic Validation
  3. Spider venom-derived peptide induces hyperalgesia in Nav1.7 knockout mice by activating Nav1.9 channels

Spider venom-derived peptide induces hyperalgesia in Nav1.7 knockout mice by activating Nav1.9 channels

  • Nat Commun. 2020 May 8;11(1):2293. doi: 10.1038/s41467-020-16210-y.
Xi Zhou # 1,  Tingbin Ma # 2,  Luyao Yang 2,  Shuijiao Peng 1,  Lulu Li 2,  Zhouquan Wang 1,  Zhen Xiao 1,  Qingfeng Zhang 1,  Li Wang 1,  Yazhou Huang 1,  Minzhi Chen 1,  Songping Liang 1,  Xianwei Zhang 3,  Jing Yu Liu 4 5,  Zhonghua Liu 6
Affiliations

Affiliations

  • 1 The National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, 410081, China.
  • 2 Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology (HUST), Wuhan, 430074, China.
  • 3 Department of Anesthesiology, Tongji Hospital of HUST, Wuhan, 430030, China.
  • 4 Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology (HUST), Wuhan, 430074, China. [email protected].
  • 5 Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, 200031, China. [email protected].
  • 6 The National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, 410081, China. [email protected].
  • # Contributed equally.
PMID: 32385249 DOI: 10.1038/s41467-020-16210-y
Abstract

The sodium channels Nav1.7, Nav1.8 and Nav1.9 are critical for pain perception in peripheral nociceptors. Loss of function of Nav1.7 leads to congenital insensitivity to pain in humans. Here we show that the spider peptide toxin called HpTx1, first identified as an inhibitor of Kv4.2, restores nociception in Nav1.7 knockout (Nav1.7-KO) mice by enhancing the excitability of dorsal root ganglion neurons. HpTx1 inhibits Nav1.7 and activates Nav1.9 but does not affect Nav1.8. This toxin produces pain in wild-type (WT) and Nav1.7-KO mice, and attenuates nociception in Nav1.9-KO mice, but has no effect in Nav1.8-KO mice. These data indicate that HpTx1-induced hypersensitivity is mediated by Nav1.9 activation and offers pharmacological insight into the relationship of the three Nav channels in pain signalling.

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