Toshiharu Azma,1,2 Akira Nishioka,1 Saori Ogawa,3 Hiroshi Nagasaka,2 Nobuyuki Matsumoto2 1Department of Anesthesiology and Pain Medicine, Kohnodai Hospital, National Center for Global Health and Medicine, Ichikawa, Chiba 272-8516, Japan; 2Department of Anesthesiology, Saitama Medical University Hospital, Moroyama-cho, Iruma-gun, Saitama 350-0495, Japan; 3Department of Dental Anesthesiology, Matsumoto Dental University, Shiojiri, Nagano 399-0781, Japan Background: The enhanced expression of endogenous opioid peptides, including β-endorphin, has been implicated in the mechanism of action of pulsed radio frequency (PRF) application in pain modulation. Because thermal effects cannot be separated from the physical property of PRF application to biological tissues, we evaluated whether temperatures higher than that of the normal body temperature (37°C) modulate mRNA expression for the precursor of β-endorphin, proopiomelanocortin (POMC) in human monocytic cells THP-1. We also attempted to examine whether mechanisms other than thermal effects also modulate such gene expression. Methods and results: The mRNA for POMC in THP-1 cells increased by a 15-minutes incubation at 42°C, 45°C, or 70°C without PRF application as compared with that in cells incubated at 37°C. On the other hand, gene expression for POMC in cells incubated at 20°C as well as at 37°C with PRF application for 15 minutes increased as compared to that in cells incubated at 37°C without PRF application. Continuous radio frequency at 70°C but not PRF provoked apoptotic cell death at 1–2 hour, and necrotic cell death at 24 hours after the RF application. Conclusion: A simple experimental system using human monocytic cells in culture demonstrated that a 15 minute elevation of temperature above 37°C enhanced gene expression for POMC in THP-1 cells, while a 15 minute application of PRF to these cells incubated at 37°C or lower, also enhanced gene expression, indicating that temperature-independent mechanisms as well as thermal effects may be involved in such gene expression. Keywords: pulsed radio frequency electric field, human monocytic cells, THP-1, proopiomelanocortin, β-endorphin, necrosis, apoptosis, apoptotic vesicle
