Conditional knockout of NaV 1.6 in adult mice ameliorates neuropathic pain

Scientific Reports
Lubin ChenSulayman D Dib-Hajj

Abstract

Voltage-gated sodium channels NaV1.7, NaV1.8 and NaV1.9 have been the focus for pain studies because their mutations are associated with human pain disorders, but the role of NaV1.6 in pain is less understood. In this study, we selectively knocked out NaV1.6 in dorsal root ganglion (DRG) neurons, using NaV1.8-Cre directed or adeno-associated virus (AAV)-Cre mediated approaches, and examined the specific contribution of NaV1.6 to the tetrodotoxin-sensitive (TTX-S) current in these neurons and its role in neuropathic pain. We report here that NaV1.6 contributes up to 60% of the TTX-S current in large, and 34% in small DRG neurons. We also show NaV1.6 accumulates at nodes of Ranvier within the neuroma following spared nerve injury (SNI). Although NaV1.8-Cre driven NaV1.6 knockout does not alter acute, inflammatory or neuropathic pain behaviors, AAV-Cre mediated NaV1.6 knockout in adult mice partially attenuates SNI-induced mechanical allodynia. Additionally, AAV-Cre mediated NaV1.6 knockout, mostly in large DRG neurons, significantly attenuates excitability of these neurons after SNI and reduces NaV1.6 accumulation at nodes of Ranvier at the neuroma. Together, NaV1.6 in NaV1.8-positive neurons does not influence pain thresholds un...Continue Reading

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Citations

Jan 24, 2019·Physiological Reviews·David L BennettSulayman D Dib-Hajj
May 2, 2019·Molecular Pain·Matthew AlsaloumUNKNOWN Propane Study Group
May 16, 2019·The Journal of Physiology·Mathilde R IsraelIrina Vetter
Jul 3, 2020·The Journal of Biological Chemistry·Agnes S ZyburaAndy Hudmon
Aug 25, 2020·Brain : a Journal of Neurology·Lubin ChenSulayman D Dib-Hajj
May 11, 2019·International Journal of Molecular Sciences·Kihwan LeeGehoon Chung
Mar 13, 2020·The Journal of Biological Chemistry·Yanling PanTheodore R Cummins
Feb 1, 2019·Annual Review of Neuroscience·Sulayman D Dib-Hajj, Stephen G Waxman
Jun 26, 2020·Physiological Reviews·Nanna Brix FinnerupTroels Staehelin Jensen
Mar 13, 2021·PloS One·Liya Y Qiao, Jonathan Madar
Mar 31, 2021·Nature Reviews. Neuroscience·George Goodwin, Stephen B McMahon
Mar 27, 2021·Physiological Reviews·Massimo MantegazzaWilliam A Catterall
Aug 7, 2021·Toxins·Rafael González-CanoFrancisco R Nieto
Apr 24, 2019·Journal of Medicinal Chemistry·John V MulcahyJohn C Hunter
Jan 1, 2020·Molecular Therapy. Methods & Clinical Development·David L HaggertyBrady Atwood

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