Two independent mouse lines carrying the Nav1.7-I228M gain-of-function variant display DRG neuron hyperexcitability but a minimal pain phenotype
Articolo
Data di Pubblicazione:
2020
Citazione:
Two independent mouse lines carrying the Nav1.7-I228M gain-of-function variant display DRG neuron hyperexcitability but a minimal pain phenotype / L. Chen, N.K. Wimalasena, J. Shim, C. Han, S. Lee, R. Gonzalez-Cano, M. Estacion, C.G. Faber, G. Lauria, S.G. Dib-Hajj, C.J. Woolf, S.G. Waxman. - In: PAIN. - ISSN 0304-3959. - (2020 Dec 11). [Epub ahead of print] [10.1097/j.pain.0000000000002171]
Abstract:
Small-fiber neuropathy (SFN), characterized by distal unmyelinated/thinly-myelinated fiber loss, produces a combination of sensory dysfunction and neuropathic pain. Gain-of-function variants in the sodium channel Nav1.7 that produce DRG neuron hyperexcitability are present in 5-10% of patients with idiopathic painful SFN. We created two independent knock-in mouse-lines carrying the Nav1.7-I228M gain-of-function variant, found in idiopathic SFN. Whole-cell patch-clamp and multi-electrode-array recordings show that Nav1.7-I228M knock-in DRG neurons are hyperexcitable compared to wild-type littermate-control neurons, but in spite of this, Nav1.7-I228M mice do not display mechanical or thermal-hyperalgesia or intraepidermal nerve-fiber loss in vivo. Therefore, while these two Nav1.7-I228M knock-in mouse lines recapitulate the DRG neuron hyperexcitability associated with gain-of function mutations in Nav1.7, they do not recapitulate the pain or neuropathy phenotypes seen in patients. We suggest that the relationship between hyper-excitability in sensory neurons and the pain experienced by these patients may be more complex than previously appreciated and highlights the challenges in modelling channelopathy pain disorders in mice.
Tipologia IRIS:
01 - Articolo su periodico
Elenco autori:
L. Chen, N.K. Wimalasena, J. Shim, C. Han, S. Lee, R. Gonzalez-Cano, M. Estacion, C.G. Faber, G. Lauria, S.G. Dib-Hajj, C.J. Woolf, S.G. Waxman
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