• Ryuji Tamura, Takayuki Nemoto, Toyoaki Maruta, Shin Onizuka, Toshihiko Yanagita, Akihiko Wada, Manabu Murakami, and Isao Tsuneyoshi.
• From the Departments of *Anesthesiology and Intensive Care and †Pharmacology, Miyazaki Medical College, University of Miyazaki, Miyazaki, Japan; ‡Department of Anesthesiology, Division of Basic Research, Washington University School of Medicine, St. Louis, Missouri; §Department of Sports Health and Welfare, Faculty of Social Welfare, Kyusyu University of Health and Welfare, Miyazaki, Japan.
• Anesth. Analg.. 2014 Feb 1;118(2):318-24.

BackgroundTumor necrosis factor-α (TNF-α) is not only a key regulator of inflammatory response but also an important pain modulator. TNF-α enhances both tetrodotoxin-sensitive (TTX-S) and tetrodotoxin-resistant Na channel currents in dorsal root ganglion (DRG) neurons. However, it remains unknown whether TNF-α affects the function and expression of the TTX-S NaV1.7 Na channel, which plays crucial roles in pain generation.MethodsWe used cultured bovine adrenal chromaffin cells expressing the NaV1.7 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-α on the expression of NaV1.7 were examined with reverse transcription-polymerase chain reaction and Western blot analysis. Results were expressed as mean ± SEM.ResultsTNFR1 and TNFR2 were expressed in adrenal chromaffin cells, as well as reported in DRG neurons. TNF-α up-regulated NaV1.7 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-α increased NaV1.7 protein up to 166% ± 24% (N = 5, corrected P < 0.0001) in adrenal chromaffin cells, concentration- and time-dependently.ConclusionsTNF-α up-regulated NaV1.7 mRNA in both adrenal chromaffin cells and DRG neurons. In addition, TNF-α up-regulated the protein expression of the TTX-S NaV1.7 channel in adrenal chromaffin cells. Our findings may contribute to understanding the peripheral nociceptive mechanism of TNF-α.

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