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

• 来源期刊: 神经科学通报（英文版）
• 年，卷（期）: 2018,（1）
• 页码范围: 22-41
• 页数: 20页
• 语种: 英文

摘要

The voltage-gated Na+ channel subtype Nav1.7 is important for pain and itch in rodents and humans.We previously showed that a Navl.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 voltagesensor domain Ⅱ of Navl.7.In contrast,rSVmab showed no or weak binding to Navl.7 in these tests.Patch-clamp recordings showed that SVmab,but not rSVmab,markedly inhibited Na+ currents in Navl.7-expressing HEK293 cells.Notably,electrical field stimulation increased the blocking activity of SVmab and rSVmab in Navl.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.