301. TNF-alpha differentially modulates ion channels of nociceptive neurons.
- Author
-
Czeschik JC, Hagenacker T, Schäfers M, and Büsselberg D
- Subjects
- Animals, Calcium Channels drug effects, Calcium Channels metabolism, Cells, Cultured, Ganglia, Spinal drug effects, Hyperalgesia metabolism, Hyperalgesia physiopathology, Ion Channel Gating drug effects, Ion Channels drug effects, Male, Membrane Potentials drug effects, Membrane Potentials physiology, Neuralgia metabolism, Neuralgia physiopathology, Neurons, Afferent drug effects, Nociceptors drug effects, Potassium Channels drug effects, Potassium Channels metabolism, Rats, Rats, Wistar, Sodium Channels drug effects, Sodium Channels metabolism, Time Factors, Tumor Necrosis Factor-alpha pharmacology, Ganglia, Spinal metabolism, Ion Channel Gating physiology, Ion Channels metabolism, Neurons, Afferent metabolism, Nociceptors metabolism, Tumor Necrosis Factor-alpha metabolism
- Abstract
Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine involved in the development and maintenance of inflammatory and neuropathic pain conditions. The mechanisms by which TNF-alpha elicits pain behavior are still incompletely understood. Numerous studies suggest that TNF-alpha sensitizes primary afferent neurons. Most recently, it was shown that TNF-alpha induced an enhancement of TTX-R Na(+) current in dorsal root ganglion (DRG) cells. In the present study, we have tested the effect of acute application of TNF-alpha on voltage-gated potassium, calcium and sodium channel currents as well as its influence on membrane conductance in isolated rat DRG neurons. We report that voltage-gated potassium channel currents of nociceptive DRG neurons are not influenced by TNF-alpha (100 ng/ml), while voltage-gated calcium channel currents were decreased voltage-dependently by -7.73+/-6.01% (S.D.), and voltage-activated sodium channels currents were increased by +5.62+/-4.27%, by TNF-alpha. In addition, TNF-alpha induced a significant increase in IV ramps at a potential of +20 mV, which did not exist when the experiments were conducted in a potassium-free solution, indicating that this effect is mainly the result of a change in potassium conductance. These different actions of TNF-alpha might help to explain how it sensitizes primary afferent neurons after nerve injury and thus facilitates pain.
- Published
- 2008
- Full Text
- View/download PDF