Discovery of a novel effect of electric field exposure on human plasma beta-endorphin and interleukin-12 levels: Insight into mechanisms of pain alleviation and defense against infection by electric field therapy

Abstract

Medical treatment using high-voltage electric potential (HELP) devices to generate an electric field (EF) is an alternative therapy commonly used in Japan, but the molecular mechanisms involved are poorly understood. Healthy human subjects were exposed to a single 15 min 18 kV stimulation of HELP, after which plasma concentrations of several peptide hormones and cytokines were examined at 0, 15, and 45 min time points using enzyme-linked immunosorbent assays (ELISA). β-Endorphin, alpha-melanocyte-stimulating hormone (α-MSH), glucagon-like peptide-1 (GLP-1), interleukin (IL)-4, IL-12, and interferon-gamma (IFN-γ) levels were significantly up-regulated after HELP exposure. Under these conditions, HELP exposure had no effect on corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), IL-6, or IL-10 levels. Because HELP exposure is known to induce up-regulation of cis-8,11,14-eicosatrienoic acid (dihomo-γ-linolenic acid; DGLA), we examined the effect of DGLA on β-endorphin secretion. In human epidermal keratinocytes, DGLA significantly induced the secretion of β-endorphins, but not α-MSH. DGLA-induced β-endorphin secretion was sensitive to the G protein-coupled receptor (GPR) 40 antagonist GW1100. Our findings provide new insights into the molecular mechanisms of pain control and defense against infection induced by EF therapy.