TNF-alpha differentially modulates ion channels of nociceptive neurons.
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.
Czeschik
Johanna Christina
JC
Institut für Physiologie, Universität Duisburg-Essen, Hufelandstrasse 55, 45122 Essen, Germany.
Hagenacker
Tim
T
Schäfers
Maria
M
Büsselberg
Dietrich
D
D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism*; D006930:Hyperalgesia / Q000378:metabolism / Q000503:physiopathology; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009437:Neuralgia / Q000378:metabolism / Q000503:physiopathology; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism*; D009619:Nociceptors / Q000187:drug effects / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism* / Q000494:pharmacology
D015220:Calcium Channels; D007473:Ion Channels; D015221:Potassium Channels; D015222:Sodium Channels; D014409:Tumor Necrosis Factor-alpha