PMID- 18314270 OWN - NLM STAT- MEDLINE DCOM- 20080710 LR - 20220331 IS - 0304-3940 (Print) IS - 0304-3940 (Linking) VI - 434 IP - 3 DP - 2008 Apr 4 TI - TNF-alpha differentially modulates ion channels of nociceptive neurons. PG - 293-8 LID - 10.1016/j.neulet.2008.01.070 [doi] AB - 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. FAU - Czeschik, Johanna Christina AU - Czeschik JC AD - Institut fur Physiologie, Universitat Duisburg-Essen, Hufelandstrasse 55, 45122 Essen, Germany. FAU - Hagenacker, Tim AU - Hagenacker T FAU - Schafers, Maria AU - Schafers M FAU - Busselberg, Dietrich AU - Busselberg D LA - eng PT - Journal Article DEP - 20080206 PL - Ireland TA - Neurosci Lett JT - Neuroscience letters JID - 7600130 RN - 0 (Calcium Channels) RN - 0 (Ion Channels) RN - 0 (Potassium Channels) RN - 0 (Sodium Channels) RN - 0 (Tumor Necrosis Factor-alpha) SB - IM MH - Animals MH - Calcium Channels/drug effects/metabolism MH - Cells, Cultured MH - Ganglia, Spinal/drug effects/*metabolism MH - Hyperalgesia/metabolism/physiopathology MH - Ion Channel Gating/drug effects/*physiology MH - Ion Channels/drug effects/*metabolism MH - Male MH - Membrane Potentials/drug effects/physiology MH - Neuralgia/metabolism/physiopathology MH - Neurons, Afferent/drug effects/*metabolism MH - Nociceptors/drug effects/*metabolism MH - Potassium Channels/drug effects/metabolism MH - Rats MH - Rats, Wistar MH - Sodium Channels/drug effects/metabolism MH - Time Factors MH - Tumor Necrosis Factor-alpha/*metabolism/pharmacology EDAT- 2008/03/04 09:00 MHDA- 2008/07/11 09:00 CRDT- 2008/03/04 09:00 PHST- 2007/12/06 00:00 [received] PHST- 2008/01/04 00:00 [revised] PHST- 2008/01/29 00:00 [accepted] PHST- 2008/03/04 09:00 [pubmed] PHST- 2008/07/11 09:00 [medline] PHST- 2008/03/04 09:00 [entrez] AID - S0304-3940(08)00153-5 [pii] AID - 10.1016/j.neulet.2008.01.070 [doi] PST - ppublish SO - Neurosci Lett. 2008 Apr 4;434(3):293-8. doi: 10.1016/j.neulet.2008.01.070. Epub 2008 Feb 6.