Effect of electromagnetic field on cyclic adenosine monophosphate (cAMP) in a human mu-opioid receptor cell model

Abstract

During the cell communication process, endogenous and exogenous signaling affect normal as well as pathological developmental conditions. Exogenous influences such as extra-low-frequency electromagnetic field (EMF) have been shown to effect pain and inflammation by modulating G-protein receptors, down-regulating cyclooxygenase-2 activity, and affecting the calcium/calmodulin/nitric oxide pathway. Investigators have reported changes in opioid receptors and second messengers, such as cyclic adenosine monophosphate (cAMP), in opiate tolerance and dependence by showing how repeated exposure to morphine decreases adenylate cyclase activity causing cAMP to return to control levels in the tolerant state, and increase above control levels during withdrawal. Resonance responses to biological systems using exogenous EMF signals suggest that frequency response characteristics of the target can determine the EMF biological response. In our past research we found significant down regulation of inflammatory markers tumor necrosis factor alpha (TNF-α) and nuclear factor kappa B (NFκB) using 5 Hz EMF frequency. In this study cAMP was stimulated in Chinese Hamster Ovary (CHO) cells transfected with human mu-opioid receptors, then exposed to 5 Hz EMF, and outcomes were compared with morphine treatment. Results showed a 23% greater inhibition of cAMP-treating cells with EMF than with morphine. In order to test our results for frequency specific effects, we ran identical experiments using 13 Hz EMF, which produced results similar to controls. This study suggests the use of EMF as a complementary or alternative treatment to morphine that could both reduce pain and enhance patient quality of life without the side-effects of opiates.

Evaluation of Cytotoxic and Genotoxic Effects of Extremely Low-frequency Electromagnetic Field on Mesenchymal Stromal Cells

“…We chose an ELF-EMF of 5 Hz, 0.4 mT field to test on MSCs/pericytes because we have used this magnetic field strength and frequency in past experiments to measure its effect on various cytokines and transcription factors involved in pain- and inflammation-related mechanisms in vitro. 4 , 5 Although we demonstrated an anti-inflammatory secretion profile in cells treated with ELF-EMF, others have reported harmful cellular effects, depending on the energy state of the field. 10 Bioelectromagnetics, the study of how living organisms interact with EMF, investigates the interaction between electrons, atoms, ions, and molecules present in all living matter, and how they are influenced by electromagnetic interactions.…”

“…Extremely low frequency electromagnetic fields (ELF-EMF) penetrate through the skin into the body’s deep tissue to affect cell function. 1 – 3 Studies report ELF-EMF to be effective in the treatment of pain and inflammation 4 – 7 and also tissue regeneration and wound healing. 8 , 9 Evidence shows that mechanisms of action include Ca 2+ ion flux, and expression/activation of Ca 2+ ion binding proteins such as calmodulin, increase the cytosolic Ca 2+ concentration to affect signaling pathways targeting tissues such as bone, cartilage, and nerve for pain regulation and tissue regeneration.…”

“… 13 Therefore, any treatment using ELF-EMF would certainly reach, and impact these cells, making them an ideal subject in which to test cytotoxicity and genotoxicity. Here, we investigated whether our known therapeutic ELF-EMF of 5 Hz, 0.4 mT field 4 , 5 could be cytotoxic/genotoxic to MSCs/pericytes upon exposure for 20 min/day, 3×/week for 2 weeks. We found that MSCs’ viability, proliferation rates, and morphological genome stability were not affected or altered by ELF-EMF, when used at the tested field strength and frequency.…”

Inhibition of the cAMP/PKA/CREB Pathway Contributes to the Analgesic Effects of Electroacupuncture in the Anterior Cingulate Cortex in a Rat Pain Memory Model

“…Years ago, it was found that increased levels of cAMP in sensory neurons indeed lead to a transient enhancement of transmitter release in the synaptic connection between sensory and motor neurons, which was regarded as a biochemical mechanism for short-term and long-term changes [13, 40]. Some studies have suggested that signaling pathways involving cAMP participate in inflammation and injury sensitization [41, 42]. Here, our study found an increased number of cAMP-positive cells in the ACC of pain memory model rats.…”

Opioid system in L-DOPA-induced dyskinesia

“…Opioid receptors relay opioid stimulation through G i or G o -mediated inhibitory intracellular signal transduction pathways [18], which may suppress G olf or G s -induced cAMP signaling in cells. For example, pharmacological activation of OPRM1 and OPRD1 blocks dopamine DRD1- or adenosine A2A-receptor-induced activation of adenylyl cyclase and reduces the production of cAMP in SPNs [51]. A reduction of cAMP levels may suppress protein kinase A (PKA) activity and leads to an aberrant activation of extracellular signal-regulated kinases (ERK1/2) in the generation of LID [52, 53].…”