The Open Pain Journal
2008, 1 : 1-7Published online 2008 November 18. DOI: 10.2174/1876386300902010001
Publisher ID: TOPAINJ-1-1
RESEARCH ARTICLE
Tumor Necrosis Factor-α Suppresses Sustained Potassium Currents in Rat Small Diameter Sensory Neurons
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
* 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.