Up-Regulation of NaV1.7 Sodium Channels Expression by Tumor Necrosis Factor- a in Cultured Bovine Adrenal Chromaffin Cells and Rat Dorsal Root Ganglion Neurons

BACKGROUND: Tumor necrosis factor- (TNF-) is not only a key regulator of inflammatory response but also an important pain modulator. TNF- enhances both tetrodotoxin-sensitive (TTX-S) and tetrodotoxin-resistant Na+ channel currents in dorsal root ganglion (DRG) neurons. However, it remains unknown whether TNF- affects the function and expression of the TTX-S Na(V)1.7 Na+ channel, which plays crucial roles in pain generation. METHODS: We used cultured bovine adrenal chromaffin cells expressing the Na(V)1.7 Na+ channel isoform and compared them with cultured rat DRG neurons. The expression of TNF receptor 1 and 2 (TNFR1 and TNFR2) in adrenal chromaffin cells was studied by Semiquantitative reverse transcription-polymerase chain reaction. The effects of TNF- on the expression of Na(V)1.7 were examined with reverse transcription-polymerase chain reaction and Western blot analysis. Results were expressed as mean SEM. RESULTS: TNFR1 and TNFR2 were expressed in adrenal chromaffin cells, as well as reported in DRG neurons. TNF- up-regulated Na(V)1.7 mRNA by 132% +/- 9% (N = 5, P = 0.004) in adrenal chromaffin cells, as well as 117% +/- 2% (N = 5, P < 0.0001) in DRG neurons. Western blot analysis showed that TNF- increased Na(V)1.7 protein up to 166% +/- 24% (N = 5, corrected P < 0.0001) in adrenal chromaffin cells, concentration- and time-dependently. CONCLUSIONS: TNF- up-regulated Na(V)1.7 mRNA in both adrenal chromaffin cells and DRG neurons. In addition, TNF- up-regulated the protein expression of the TTX-S Na(V)1.7 channel in adrenal chromaffin cells. Our findings may contribute to understanding the peripheral nociceptive mechanism of TNF-.