TNF-α differentially modulates ion channels of nociceptive neurons

Tumor necrosis factor-α (TNF-α) is a proinflammatory cytokine involved in the development and maintenance of inflammatory and neuropathic pain conditions. The mechanisms by which TNF-α elicits pain behavior are still incompletely understood. Numerous studies suggest that TNF-α sensitizes primary afferent neurons. Most recently, it was shown that TNF-α 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-α 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-α (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-α. In addition, TNF-α 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-α might help to explain how it sensitizes primary afferent neurons after nerve injury and thus facilitates pain.