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 / 神经科学通报·英文版

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.

The Chemical Markers of Plant Lectin B4 in the Enteric Nervous System of Mice / 医学研究杂志

Objective To investigate the relationship of the chemical coding enteric nervous system of the mice and expression for neurotransmittor of enteric primary afferent neurons for Nociceptors.Methods Immunocytochemical and morphometric techniques were used to quantify the distribution of IB4-containing neurons in mice enteric nervous system using three mice chiocing every vision 50 neurons undering confocal microscopy IB4 immunolabelling and colocalized with calretinin and lectin B4.Results IB4 being binded to primary afferent neurons of enteric pleuxes happend in small intestin and colon of mice,where it was selective for nociceptive neurons.IB4 revealed large round or oval(Dogiel type II)neurons,type I neurons with prominent laminar dendrites and small neurons of myenteric ganglia.The type II neurons were immunoreactive for calretinin,and some type I neurons were immunoreactive for nitric oxide synthase.Most neurons in the submucosal ganglia bound IB4,and some of these were vasoactive intestinal peptide immunoreactive.Conclusion The results indicate that IB4 labels specific subgroups of enteric neurons in the enteric nervous system of the mice.These include intrinsic primary afferent neurons,but other neurons,including secretomotor neurons,are labeled.The results suggest that IB4 is not a specific label for enteric nociceptive neurons.