| First Author | Salvatierra J | Year | 2018 |
| Journal | J Clin Invest | Volume | 128 |
| Issue | 12 | Pages | 5434-5447 |
| PubMed ID | 30395542 | Mgi Jnum | J:270913 |
| Mgi Id | MGI:6276491 | Doi | 10.1172/JCI122481 |
| Citation | Salvatierra J, et al. (2018) A disease mutation reveals a role for NaV1.9 in acute itch. J Clin Invest 128(12):5434-5447 |
| abstractText | Itch (pruritis) and pain represent two distinct sensory modalities; yet both have evolved to alert us to potentially harmful external stimuli. Compared with pain, our understanding of itch is still nascent. Here, we report a new clinical case of debilitating itch and altered pain perception resulting from the heterozygous de novo p.L811P gain-of-function mutation in NaV1.9, a voltage-gated sodium (NaV) channel subtype that relays sensory information from the periphery to the spine. To investigate the role of NaV1.9 in itch, we developed a mouse line in which the channel is N-terminally tagged with a fluorescent protein, thereby enabling the reliable identification and biophysical characterization of NaV1.9-expressing neurons. We also assessed NaV1.9 involvement in itch by using a newly created NaV1.9-/- and NaV1.9L799P/WT mouse model. We found that NaV1.9 is expressed in a subset of nonmyelinated, nonpeptidergic small-diameter dorsal root ganglia (DRGs). In WT DRGs, but not those of NaV1.9-/- mice, pruritogens altered action potential parameters and NaV channel gating properties. Additionally, NaV1.9-/- mice exhibited a strong reduction in acute scratching behavior in response to pruritogens, whereas NaV1.9L799P/WT mice displayed increased spontaneous scratching. Altogether, our data suggest an important contribution of NaV1.9 to itch signaling. |
