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A disease mutation reveals a role for Nav1.9 in acute itch

(2018) JOURNAL OF CLINICAL INVESTIGATION. 128(12). p.5434-5447
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Abstract
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 Na(V)1.9, a voltage-gated sodium (Na-V) channel subtype that relays sensory information from the periphery to the spine. To investigate the role of Na(V)1.9 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 Na(V)1.9-expressing neurons. We also assessed Na(V)1.9 involvement in itch by using a newly created Na(V)1.9(-/-) and Na(V)1.9(L799P/WT) mouse model. We found that Na(V)1.9 is expressed in a subset of nonmyelinated, nonpeptidergic small-diameter dorsal root ganglia (DRGs). In WT DRGs, but not those of Na(V)1.9(-/-) mice, pruritogens altered action potential parameters and Na-V channel gating properties. Additionally, Na(V)1.9(-/-) mice exhibited a strong reduction in acute scratching behavior in response to pruritogens, whereas Na(V)1.9(L799P/WT) mice displayed increased spontaneous scratching. Altogether, our data suggest an important contribution of Na(V)1.9 to itch signaling.
Keywords
SODIUM-CHANNEL NAV1.9, PROTEIN-COUPLED RECEPTORS, PAIN SENSATION, NEURONS, TRANSMISSION, LOCALIZATION, EXCITABILITY, NOCICEPTORS, AFFERENTS, EFFICIENT

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Citation

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MLA
Salvatierra, Juan, Marcelo Diaz-Bustamante, James Meixiong, et al. “A Disease Mutation Reveals a Role for Nav1.9 in Acute Itch.” JOURNAL OF CLINICAL INVESTIGATION 128.12 (2018): 5434–5447. Print.
APA
Salvatierra, Juan, Diaz-Bustamante, M., Meixiong, J., Tierney, E., Dong, X., & Bosmans, F. (2018). A disease mutation reveals a role for Nav1.9 in acute itch. JOURNAL OF CLINICAL INVESTIGATION, 128(12), 5434–5447.
Chicago author-date
Salvatierra, Juan, Marcelo Diaz-Bustamante, James Meixiong, Elaine Tierney, Xinzhong Dong, and Frank Bosmans. 2018. “A Disease Mutation Reveals a Role for Nav1.9 in Acute Itch.” Journal of Clinical Investigation 128 (12): 5434–5447.
Chicago author-date (all authors)
Salvatierra, Juan, Marcelo Diaz-Bustamante, James Meixiong, Elaine Tierney, Xinzhong Dong, and Frank Bosmans. 2018. “A Disease Mutation Reveals a Role for Nav1.9 in Acute Itch.” Journal of Clinical Investigation 128 (12): 5434–5447.
Vancouver
1.
Salvatierra J, Diaz-Bustamante M, Meixiong J, Tierney E, Dong X, Bosmans F. A disease mutation reveals a role for Nav1.9 in acute itch. JOURNAL OF CLINICAL INVESTIGATION. 2018;128(12):5434–47.
IEEE
[1]
J. Salvatierra, M. Diaz-Bustamante, J. Meixiong, E. Tierney, X. Dong, and F. Bosmans, “A disease mutation reveals a role for Nav1.9 in acute itch,” JOURNAL OF CLINICAL INVESTIGATION, vol. 128, no. 12, pp. 5434–5447, 2018.
@article{8584492,
  abstract     = {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 Na(V)1.9, a voltage-gated sodium (Na-V) channel subtype that relays sensory information from the periphery to the spine. To investigate the role of Na(V)1.9 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 Na(V)1.9-expressing neurons. We also assessed Na(V)1.9 involvement in itch by using a newly created Na(V)1.9(-/-) and Na(V)1.9(L799P/WT) mouse model. We found that Na(V)1.9 is expressed in a subset of nonmyelinated, nonpeptidergic small-diameter dorsal root ganglia (DRGs). In WT DRGs, but not those of Na(V)1.9(-/-) mice, pruritogens altered action potential parameters and Na-V channel gating properties. Additionally, Na(V)1.9(-/-) mice exhibited a strong reduction in acute scratching behavior in response to pruritogens, whereas Na(V)1.9(L799P/WT) mice displayed increased spontaneous scratching. Altogether, our data suggest an important contribution of Na(V)1.9 to itch signaling.},
  author       = {Salvatierra, Juan and Diaz-Bustamante, Marcelo and Meixiong, James and Tierney, Elaine and Dong, Xinzhong and Bosmans, Frank},
  issn         = {0021-9738},
  journal      = {JOURNAL OF CLINICAL INVESTIGATION},
  keywords     = {SODIUM-CHANNEL NAV1.9,PROTEIN-COUPLED RECEPTORS,PAIN SENSATION,NEURONS,TRANSMISSION,LOCALIZATION,EXCITABILITY,NOCICEPTORS,AFFERENTS,EFFICIENT},
  language     = {eng},
  number       = {12},
  pages        = {5434--5447},
  title        = {A disease mutation reveals a role for Nav1.9 in acute itch},
  url          = {http://dx.doi.org/10.1172/jci122481},
  volume       = {128},
  year         = {2018},
}

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