Douleur - page 7 - Publications Scientifiques

Dernière publication 19/02/2018

Conditional knockout of NaV1-6 in adult mice ameliorates neuropathic pain

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...

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    [title] => Conditional knockout of NaV1-6 in adult mice ameliorates neuropathic pain
    [paragraph] => Conditional knockout of NaV1.6 in adult mice ameliorates neuropathic pain
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Authors
L. Chen, J. Huang, P. Zhao. AK Persson, FB Dib-Hajj, X Cheng, A Tan, S Wanman, SD Dib-Hajj

 Lab
Yale University School of Medicine, New Haven, CT, USA
Journal
Scientific Reports
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 under normal or pathological conditions, but NaV1.6 in large NaV1.8-negative DRG neurons plays an important role in neuropathic pain.
BIOSEB Instruments Used
Thermal Place Preference, 2 Temperatures Choice Nociception Test (BIO-T2CT)
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Un test indépendant de l'opérateur pour étudier les seuils de douleur chez les rongeurs (rats et souris) par l'évaluation de la préférence de température (zone de confort thermal) - un outil innovant pour vos recherches sur l'analgésie et la nociception, ouvrant de nouveaux champs d'étude, et une solution idéale pour le screening de médicaments analgésiques et nociceptifs. Désormais fourni avec un nouveau logiciel dernier cri permettant de monitorer l'activité et les transitions de température rapides!

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