PMID- 24445633 OWN - NLM STAT- MEDLINE DCOM- 20140318 LR - 20210902 IS - 1526-7598 (Electronic) IS - 0003-2999 (Linking) VI - 118 IP - 2 DP - 2014 Feb TI - Up-regulation of NaV1.7 sodium channels expression by tumor necrosis factor-alpha in cultured bovine adrenal chromaffin cells and rat dorsal root ganglion neurons. PG - 318-324 LID - 10.1213/ANE.0000000000000085 [doi] AB - BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) is not only a key regulator of inflammatory response but also an important pain modulator. TNF-alpha enhances both tetrodotoxin-sensitive (TTX-S) and tetrodotoxin-resistant Na channel currents in dorsal root ganglion (DRG) neurons. However, it remains unknown whether TNF-alpha affects the function and expression of the TTX-S NaV1.7 Na channel, which plays crucial roles in pain generation. METHODS: We 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-alpha on the expression of NaV1.7 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-alpha 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-alpha increased NaV1.7 protein up to 166% +/- 24% (N = 5, corrected P < 0.0001) in adrenal chromaffin cells, concentration- and time-dependently. CONCLUSIONS: TNF-alpha up-regulated NaV1.7 mRNA in both adrenal chromaffin cells and DRG neurons. In addition, TNF-alpha 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-alpha. FAU - Tamura, Ryuji AU - Tamura R AD - 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. FAU - Nemoto, Takayuki AU - Nemoto T FAU - Maruta, Toyoaki AU - Maruta T FAU - Onizuka, Shin AU - Onizuka S FAU - Yanagita, Toshihiko AU - Yanagita T FAU - Wada, Akihiko AU - Wada A FAU - Murakami, Manabu AU - Murakami M FAU - Tsuneyoshi, Isao AU - Tsuneyoshi I LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Anesth Analg JT - Anesthesia and analgesia JID - 1310650 RN - 0 (Actins) RN - 0 (NAV1.7 Voltage-Gated Sodium Channel) RN - 0 (Receptors, Tumor Necrosis Factor, Type I) RN - 0 (Receptors, Tumor Necrosis Factor, Type II) RN - 0 (Scn9a protein, rat) RN - 0 (Tnfrsf1a protein, rat) RN - 0 (Tumor Necrosis Factor-alpha) RN - 4368-28-9 (Tetrodotoxin) RN - 9NEZ333N27 (Sodium) SB - IM MH - Actins/metabolism MH - Adrenal Glands/*metabolism MH - Animals MH - Cattle MH - Chromaffin Cells/*cytology MH - Dose-Response Relationship, Drug MH - Female MH - Ganglia, Spinal/*metabolism MH - Male MH - NAV1.7 Voltage-Gated Sodium Channel/*metabolism MH - Neuralgia/drug therapy MH - Neurons/*metabolism MH - Rats MH - Receptors, Tumor Necrosis Factor, Type I/metabolism MH - Receptors, Tumor Necrosis Factor, Type II/metabolism MH - Reverse Transcriptase Polymerase Chain Reaction MH - Sodium/chemistry MH - Tetrodotoxin/chemistry MH - Time Factors MH - Tumor Necrosis Factor-alpha/*metabolism MH - Up-Regulation EDAT- 2014/01/22 06:00 MHDA- 2014/03/19 06:00 CRDT- 2014/01/22 06:00 PHST- 2014/01/22 06:00 [entrez] PHST- 2014/01/22 06:00 [pubmed] PHST- 2014/03/19 06:00 [medline] AID - 00000539-201402000-00013 [pii] AID - 10.1213/ANE.0000000000000085 [doi] PST - ppublish SO - Anesth Analg. 2014 Feb;118(2):318-324. doi: 10.1213/ANE.0000000000000085.