Sensitization of voltage activated calcium channel currents for capsaicin in nociceptive neurons by tumor-necrosis-factor-α

It is known that application of tumor-necrosis-factor-α (TNF-α) sensitizes neuronal calcium channels for heat stimuli in rat models of neuropathic pain. This study examines whether TNF-α modulates the capsaicin-induced effects after transient receptor potential vanilloid (TRPV)-1 receptor activation on voltage activated calcium channel currents (ICa(V)).TRPV-1 receptors are activated by heat and play an important role in the pathogenesis of thermal hyperalgesia in neuropathic pain syndromes, while voltage activated channels are essential for transmission of neuronal signals.Eliciting ICa(V) in DRG neurons of rats by a depolarization from the resting potential to 0 mV, TNF-α (100 ng/ml) reduces ICa(V) by 16.9 ± 2.2%, while capsaicin (0.1 μM) decreases currents by 27 ± 4.3%. Pre-application of TNF-α (100 ng/ml) for 24 h results in a sensitization of ICa(V) to capsaicin (0.1 μM) with a reduction of 42.8 ± 4.4% mediated by TRPV-1. While L-type (36.6 ± 5.2%) and P/Q-type currents (35.6 ± 4.1%) are also sensitized by TRPV-1 activation, N-type channel currents are most sensitive (74.5 ± 7.3%). The capsaicin-induced shift towards the hyperpolarizing voltage range does not occur when TNF-α is applied. Summarizing, TNF-α sensitizes nociceptive neurons for capsaicin.