Two independent mouse lines carrying the Nav1.7 I228M gain-of-function variant display dorsal root ganglion neuron hyperexcitability but a minimal pain phenotype

Authors: Chen L, Wimalasena NK, Shim J, Han C, Lee SI, Gonzalez-Cano R, Estacion M, Faber CG, Lauria G, Dib-Hajj SD, Woolf CJ, and Waxman SG.

Pain, 2021.

Summary:

Researchers use bioelectronic assays to investigate the mechanisms of pain symptoms associated with small-fiber neuropathy 

Small-fiber neuropathy (SFN) is a condition that causes severe pain and other sensory disturbances, primarily in the feet and hands. Research has shown that some cases of SFN are related to a mutation in the Scn9a gene, which codes the voltage-gated sodium channel Nav1.7 associated with nociceptor excitability and pain signaling, but the mechanisms underlying pain symptoms and axonal degeneration in SFN are not fully understood. In this study, researchers examine dorsal root ganglion (DRG) neurons from two independent knock-in mouse lines generated with targeted homologous recombination and CRISPR editing.

To explore neural activity in the DRG neurons carrying the Nav1.7 gain-of-function variant, the scientists used Axion’s Maestro multielectrode array (MEA) platform. Findings from MEA and other testing methods revealed that the neurons were hyperexcitable compared to controls, although they did not recapitulate the pain or neuropathy phenotypes observed in patients with SFN. These results suggest that the link between hyperexcitability in sensory neurons and pain symptoms in SFN may be more complex than previously thought.