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Neuroscience Bulletin

, Volume 34, Issue 1, pp 22–41 | Cite as

Differential Inhibition of Nav1.7 and Neuropathic Pain by Hybridoma-Produced and Recombinant Monoclonal Antibodies that Target Nav1.7

Differential activities of Nav1.7-targeting monoclonal antibodies
  • Sangsu Bang
  • Jiho Yoo
  • Xingrui Gong
  • Di Liu
  • Qingjian Han
  • Xin Luo
  • Wonseok Chang
  • Gang Chen
  • Sang-Taek Im
  • Yong Ho Kim
  • Judith A. Strong
  • Ma-Zhong Zhang
  • Jun-Ming ZhangEmail author
  • Seok-Yong LeeEmail author
  • Ru-Rong JiEmail author
Original Article

Abstract

The voltage-gated Na+ channel subtype Nav1.7 is important for pain and itch in rodents and humans. We previously showed that a Nav1.7-targeting monoclonal antibody (SVmab) reduces Na+ currents and pain and itch responses in mice. Here, we investigated whether recombinant SVmab (rSVmab) binds to and blocks Nav1.7 similar to SVmab. ELISA tests revealed that SVmab was capable of binding to Nav1.7-expressing HEK293 cells, mouse DRG neurons, human nerve tissue, and the voltage-sensor domain II of Nav1.7. In contrast, rSVmab showed no or weak binding to Nav1.7 in these tests. Patch-clamp recordings showed that SVmab, but not rSVmab, markedly inhibited Na+ currents in Nav1.7-expressing HEK293 cells. Notably, electrical field stimulation increased the blocking activity of SVmab and rSVmab in Nav1.7-expressing HEK293 cells. SVmab was more effective than rSVmab in inhibiting paclitaxel-induced mechanical allodynia. SVmab also bound to human DRG neurons and inhibited their Na+ currents. Finally, potential reasons for the differential efficacy of SVmab and rSVmab and future directions are discussed.

Keywords

Primary afferent neuron Patch clamping (electrophysiology) Sodium channels Animal models 

Notes

Acknowledgements

This work was supported by National Institutes of Health Grants R01NS89479, R01NS045594 and R01NS055860.

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Copyright information

© Shanghai Institutes for Biological Sciences, CAS and Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  1. 1.Department of AnesthesiologyDuke University Medical CenterDurhamUSA
  2. 2.Department of BiochemistryDuke University Medical CenterDurhamUSA
  3. 3.Pain Research Center, Department of AnesthesiologyUniversity of CincinnatiCincinnatiUSA
  4. 4.Department of AnesthesiologyShanghai Children’s Medical CenterShanghaiChina
  5. 5.Department of Physiology and Biophysics, College of MedicineEulji UniversityDaejeonKorea
  6. 6.Department of Physiology, College of MedicineGachon UniversityIncheonKorea

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