1Department of Anesthesiology, Duke University Medical Center, 595 LaSalle St, Durham, NC 27710, USA
2Department of Biochemistry, Duke University Medical Center, 303 Research Drive, Durham, NC 27710, USA
3Pain Research Center, Department of Anesthesiology, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH 45267-0531, USA
4Department of Anesthesiology, Shanghai Children’s Medical Center, Shanghai 200127, China
5Department of Physiology and Biophysics, College of Medicine, Eulji University, 143-5 Yongdu-Dong, Jung-Gu, Daejeon 34824, Korea
6Department of Physiology, College of Medicine, Gachon University, Incheon 21999, Korea

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

[SpringerLink]