Modulation of Voltage-Gated Sodium Channels by Activation of Tumor Necrosis Factor Receptor-1 and Receptor-2 in Small DRG Neurons of RatsReportar como inadecuado




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Mediators of Inflammation - Volume20152015, Article ID124942, 8 pages -

Research ArticleDepartment of Neurology, University of Duisburg-Essen, Germany

Received 2 July 2015; Revised 10 August 2015; Accepted 18 August 2015

Academic Editor: MauricioRetamal

Copyright 2015 M.
Leo et al.
This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Tumor necrosis factor- TNF- is a proinflammatory cytokine involved in the development and maintenance of inflammatory and neuropathic pain.
Its effects are mediated by two receptors, TNF receptor-1 TNFR-1 and TNF receptor-2 TNFR-2.
These receptors play a crucial role in the sensitization of voltage-gated sodium channels VGSCs, a key mechanism in the pathogenesis of chronic pain.
Using the whole-cell patch-clamp technique, we examined the influence of TNFR-1 and TNFR-2 on VGSCs and TTX-resistant NaV1.8 channels in isolated rat dorsal root ganglion neurons by using selective TNFR agonists.
The TNFR-1 agonist R32W 10pg-mL caused an increase in the VGSC current INaV by 27.2 5.1%, while the TNFR-2 agonist D145 10pg-mL increased the current by 44.9 2.6%.
This effect was dose dependent.
Treating isolated NaV1.8 with R32W 100pg-mL resulted in an increase in INaV1.8 by 18.9 1.6%, while treatment with D145 100pg-mL increased the current by 14.5 3.7%.
Based on the current-voltage relationship, 10pg of R32W or D145 led to an increase in INaV in a bell-shaped, voltage-dependent manner with a maximum effect at 30mV.
The effects of TNFR activation on VGSCs promote excitation in primary afferent neurons and this might explain the sensitization mechanisms associated with neuropathic and inflammatory pain.





Autor: M.
Leo,S.
Argalski,M.
Schfers,and T.
Hagenacker


Fuente: https://www.hindawi.com/



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