Abstract

The somatosensory nervous system perceives and transfers sensory modalities such as pain and itch from the periphery to the sensory cortex. Pain continues to be extensively researched, whereas itch remains overlooked. An antagonistic relationship between the two has long been suggested and is becoming gradually more defined. Voltage-gated sodium channel (Nav) 1.9 has been implicated in pain-related syndromes. Three unrelated cases of congenital insensitivity to pain were reported to have a de novo heterozygous p.L811P gain-of-function mutation in Nav1.9 (SCN11A). Patients were also affected by severe pruritus. This suggests Nav1.9 as a key player in pruritic circuits. In this project we characterize Nav1.9-expressing neurons and assess its involvement in mouse chronic scratching behavior. To visualize Nav1.9 in the CNS through immunofluorescent imaging, a mouse line was created in which the channel is fused to superfolder GFP. Scratching behavior in wild-type and knock-out mice was observed upon triggering acute or chronic itch, respectively achieved through chloroquine injections and topical application of 1% squaric acid dibutylester (SADBE). Electrophysiological data was collected by performing the patch clamp technique on spinal cord slices of the sfGFP-tagged mouse line. Nav1.9 expression has been observed in the dorsal horn of the spinal cord and in various regions throughout the brain. Preliminary data of the SADBE itch assays show little to no response in KO mice, whereas WT mice develop chronic scratching behavior. Electrophysiological experiments are still ongoing and as of now inconclusive. We have uncovered expression in regions of the CNS that were previously undocumented. Electrophysiological data is needed to define and characterize the Nav1.9-expressing neurons. Preliminary behavioral data indicates a transmissive role for Nav1.9 in the sensory perception of itch, but more data is needed to establish these findings.

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