RESEARCH ARTICLE


Tumor Necrosis Factor-α Suppresses Sustained Potassium Currents in Rat Small Diameter Sensory Neurons



Bao-Gang Liu2, , Maxim Dobretsov2, Joseph R. Stimers3, Jun-Ming Zhang*, 1, 2
1 Department of Anesthesiology, University of Cincinnati, Cincinnati, OH, USA
2 Department of Anesthesiology, University of Arkansas for Medical Sciences, Little Rock, AR
3 Pharmacology & Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR
Current address: Department of Anesthesiology, Winston-Salem, Wake Forest University, NC


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Creative Commons License
© 2008 Liu et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the Pain Research Center,Department of Anesthesiology, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH 45267-0531, USA; E-mail: Jun-Ming.Zhang@uc.edu


Abstract

Tumor necrosis factor-α (TNF-α), a pro-inflammatory cytokine, produces pain and hyperalgesia by activating and/or sensitizing nociceptive sensory neurons. In the present study, using whole-cell patch clamp techniques, the regulation of potassium currents by TNF-α was examined in acutely dissociated small dorsal root ganglion neurons. We found that acute application of TNF-α inhibited, in a dose-dependent manner, the non-inactivating sustained potassium current without changing the rapidly inactivating transient current or the voltage-dependence of steady-state inactivation. The effects of TNF-α on potassium currents were similar to that of prostaglandin E2 as reported previously and also demonstrated in the current study. Furthermore, indomethacin, a potent inhibitor for both cyclo-oxygenase (COX)-1 and COX-2, completely blocked the effect of TNF-α on potassium currents. These results suggest that TNF-α may sensitize or activate sensory neurons by suppressing the sustained potassium current in nociceptive DRG neurons, possibly via stimulating the intracellular production i.e. the synthesis and/or release of endogenous prostaglandins.

Keywords: Tumor Necrosis Factor-α (TNF-α), Dorsal Root Ganglion (DRG), Potassium Currents, Prostaglandins, Indomethacin.