Antinociceptive effects of low-intensity extrahigh-frequency electromagnetic radiation

We studied the effect of low-intensity extrahigh-frequency (EHF) electromagnetic radiation (EMR) on changes of behavior phenomena in rats observed under conditions of experimentally induced tonic somatic, visceral, and acute thermal pain. Preliminary irradiation of the animals with EHF EMR was found to exert clear antinociceptive effects. Decreases in the intensity of pain reactions were observed under conditions of both single and repeated irradiation sessions. Neirofiziologiya/Neurophysiology, Vol. 38, No. 4, pp. 331–341, July–August, 2006.     

Effects of the blockade of the system of opioid peptides on changes in emotional/behavioral reactions of rats induced by the action of extrahigh-frequency electromagnetic radiation in the norm and under conditions of hypokinetic stress

We studied the effects of pharmacological blockade (by injections of naloxone) of the system of opioid peptides on changes in emotional/behavioral reactions of rats in the open-field test. These changes were caused by the isolated action of low-intensity electromagnetic radiation (EMR) of extrahigh frequency (EHF) and its combination with experimentally induced hypokinetic stress. We conclude that one of the mechanisms of physiological effects of low-intensity EHF EMR is an increase in the functional activity of the system of regulatory opioid peptides; this results in adaptive modifications of the emotional/behavioral reactions under new conditions of the open-field test and provide an anti-stress effect under conditions of hypokinetic stress. Neirofiziologiya/Neurophysiology, Vol. 38, No. 1, pp. 52–60, January–February, 2006.     

Modifications of Motor Asymmetry in Rats under the Influence of Low-Intensity Extra High-Frequency Electromagnetic Radiation in the Norm and under Stress Conditions

We studied modifications of motor asymmetry in rats with different motor lateralization (dextrals, sinistrals, and ambidextrals) induced by low-intensity extra high-frequency (EHF) electromagnetic radiation (EMR), hypokinetic stress, and their combination. It was found that the development of hypokinetic stress in rats induced by limitation of their mobility results in a considerable decrease of the coefficient of motor asymmetry (up to inversion of its sign); this can be related to a decrease in the resistivity to stressing and adaptability of the organism to the influence of external factors. The influence of EHF EMR on the animals under conditions of both normal and limited motor activity resulted in an increase in the index of motor lateralization in animals of all phenotypic groups under study; probably, this helped to increase the adaptive capabilities of the organism. Neirofiziologiya/Neurophysiology, Vol. 37, No. 2, pp. 164–168, March–April, 2005.     

Effects of melatonin and antagonists of MT1 and MT2 receptors on somatic pain induced within the fixed circadian rhythm

We studied behavioral pain-related reactions (PRRs) induced in mice by subcutaneous injections of 5% formalin within different phases of the fixed circadian illumination rhythm under conditions of administration of exogenous melatonin and of blocking of MT1 and MT2 melatonin receptors. It was demonstrated that modulation of experimentally induced somatic pain depends considerably on the phase of the preset circadian rhythm. In the norm, the duration of PRRs in the middle of the dark phase was 30% smaller than that in the middle of the light phase. Administration of exogenous melatonin in the middle of the light phase decreased the duration of episodes of noxious behavior by 43%, on average. Injections of melatonin within the dark phase resulted in no significant changes in the duration of PRRs. In the dark phase, the blockade of MT1 receptors by luzindole led to an increase in the duration of PRRs by 45%, as compared with the norm, while in the light phase we observed no significant alterations of this duration under conditions of blocking of the above-mentioned receptors. The blockade of MT2 receptors by prazocine in the middle of dark and light phases increased the durations of PRRs by 92 and 28%, respectively. Our data indicate that the analgesic effect of melatonin depends significantly on the level of this hormone in the organism; in turn, such a level is determined by the illumination conditions. The antinoxious effect of melatonin is mediated by MT receptors, in particular by MT2 receptors. Neirofiziologiya/Neurophysiology, Vol. 39, No. 3, pp. 255–259, May–June, 2007.     

Suppression of nonspecific resistance of the body under the effect of extremely high frequency electromagnetic radiation of low intensity

The dynamics of leukocyte number and functional activity of peripheral blood neutrophils under whole-body exposure of healthy mice to low-intensity extremely-high-frequency electromagnetic radiation (EHF EMR, 42.0 GHz, 0.15 mW/cm2, 20 min daily) was studied. It was shown that the phagocytic activity of peripheral blood neutrophils was suppressed by about 50% (p < 0.01 as compared with the sham-exposed control) in 2-3 h after the single exposure to EHF EMR. The effect persisted for 1 day after the exposure, and then the phagocytic activity of neutrophils returned to the norm within 3 days. A significant modification of the leukocyte blood profile in mice exposed to EHF EMR for 5 days was observed after the cessation of exposures: the number of leukocytes increased by 44% (p < 0.05 as compared with sham-exposed animals), mostly due to an increase in the lymphocyte content. The supposition was made that EHF EMR effects can be mediated via the metabolic systems of arachidonic acid and the stimulation of adenylate cyclase activity, with subsequent increase in the intracellular cAMP level. The results indicated that the whole-body exposure of healthy mice to low-intensity EHF EMR has a profound effect on the indices of nonspecific immunity.     

Role of phospholipase A2 and epoxygenase in inhibition of respiration burst in neutrophils by low intensity radiation of extremely high frequency

The role of some components of the phospholipid metabolism in the activation of neutrophil respiratory burst and its inhibition by electromagnetic radiation (EMR) of extremely high frequencies (EHF) was studied. It was shown that EHF EMR has effect on cells with a high sensitivity to the inhibitor of phospholipase A2 4-bromophenacyl bromide. However, againsts the background of the inhibitor, the effect of EHF EMR was not observed on cells with either high or low sensitivity to the inhibitor. EHF EMR was also inefficient with cells pretreated with proadifen, an inhibitor of epoxygenase (cytochrome P-450). The results obtained suggest that the effect of EHF EMR manifests itself in cells with a high activity of phospholipase A2 and is realized with the participation of epoxygenase metabolites of arachidonic acid.     

Behavioral responses to phasic nociceptive stimulation occurring on the background of a tonic pain focus in ontogeny of the rabbit

The effect of a focus of tonic pain (a subcutaneous injection of formalin into the dorsal field of the shin) on the thresholds of a defense reaction, an attempt to jump out of the chamber in response to a nociceptive electrocutaneous stimulation of the hindpaw1, was studied in the 20– 25-day-old and adult rabbits. The tonic pain produces a biphasic reduction of the defense reaction threshold. At the first phase, hyperalgesia is more pronounced than in the second one, but its duration is shorter. Changes in pain sensitivity in the rabbits proceed in the same direction in both age groups and coincide in time with increase of specific behavioral responses to the formalin injection (licking and shaking the paw). In the 20–25-day-old rabbits the reduction of the threshold of the defense reaction and duration of hyperalgesia phases are more pronounced than in adult animals. Deceased.     

Background activity of neurons of the supraoptic hypothalamic nucleus in rats under conditions of vibrational stimulation and electromagnetic extrahigh-frequency irradiation

We analyzed background impulse activity of neurons of the supraoptic nucleus of the rat hypothalamus in the course of 15-day-long isolated action of generalized vibrational stimulation and combination of such stimulation with irradiation of the animal’s head with low-intensity extrahigh-frequency (EHF, millimeter-range) electromagmetic waves. The distributions of the neurons by the level of regularity and dynamics of spike trains, separate frequency ranges of impulsation, and pattern of interspike interval (ISI) histograms were estimated. We also calculated the mean frequency of discharges and coefficient of variation of ISIs. A trend toward decreases in the deviations of some parameters of neuronal spike activity generated by supraoptic neurons, which were evident within early time intervals of isolated action of vibration (5 to 10 days), was observed under the influence of EHF electromagnetic irradiation; thus, the latter factor probably exerts a sedative effect. Neirofiziologiya/Neurophysiology, Vol. 39, No. 6, pp. 433–442, November–December, 2007.     

Anti-inflammatory effects of low-intensity extremely high-frequency electromagnetic radiation: frequency and power dependence

Using a model of acute zymosan-induced footpad edema in NMRI mice, the frequency and power dependence of anti-inflammatory effect of low-intensity extremely high-frequency electromagnetic radiation (EHF EMR) was found. Single whole-body exposure of animals to EHF EMR at the intensity of 0.1 mW/cm(2) for 20 min at 1 h after zymosan injection reduced both the footpad edema and local hyperthermia on average by 20% at the frequencies of 42.2, 51.8, and 65 GHz. Some other frequencies from the frequency range of 37.5-70 GHz were less effective or not effective at all. At fixed frequency of 42.2 GHz and intensity of 0.1 mW/cm(2), the effect had bell-shaped dependence on exposure duration with a maximum at 20-40 min. Reduction of intensity to 0.01 mW/cm(2) resulted in a change of the effect dependence on exposure duration to a linear one. Combined action of cyclooxygenase inhibitor sodium diclofenac and EHF EMR exposure caused a partial additive effect of decrease in footpad edema. Combined action of antihistamine clemastine and EHF EMR exposure caused a dose-dependent abolishment of the anti-inflammatory effect of EHF EMR. The results obtained suggest that arachidonic acid metabolites and histamine are involved in realization of anti-inflammatory effects of low-intensity EHF EMR.     

Decrease in the intensity of the cellular immune response and nonspecific inflammation upon exposure to extremely high frequency electromagnetic radiation

The effect of low-intensity extremely high-frequency electromagnetic radiation (EHF EMR, 42.0 GHz, 0.1 mW/cm2, 20 min daily) on cell-mediated immunity and nonspecific inflammatory response in mice was studied. The intensity of cell-mediated immune response in the reaction of delayed-type hypersensitivity and nonspecific inflammation was estimated by a relative increase in the thickness of foot pad after immunization of animals by sheep red blood cells or zymosan. It was shown for the first time that the radiation reduces both immune and nonspecific inflammatory responses. It was shown with the use of models of acute inflammation and full-thickness skin wounds that EHF EMR suppresses the nonspecific inflammatory response but does not influence the duration of the pathological process. We suppose that the basis of the effects revealed is the modification of functional activity of phagocytic cells under the influence of EHF EMR. The results suggest that some therapeutic effects of EHF EMR can be realized via the inhibition of inflammatory processes.     

Effect of millimeter band electromagnetic radiation on a culture of sensory neurons from the chick embryo

The effect of extra-high frequency electromagnetic radiation (EHF EMR) on the development of organotypical culture of the spinal ganglia of a 9–10 day-old chick embryo was investigated. EMR with a wavelength of 5.6 mm and a rate of flow density <1.0, 4.0, and >100 mW/cm² was used. The stimulating action of EMR at rate of flow density of 4.0 mW/cm², manifested in intensification of the growth of neurites of sensory neurons and the proliferation of the peripheral glia, was observed. EHF EMR with a density >100 mW/cm² exerted inhibitory influence. The possibility of using the stimulating effect of EHF EMR in medical practice for intensifying regeneration in pathology and after trauma of the peripheral nervous system is discussed.Neirofiziologiya/Neurophysiology, Vol. 25, No. 3, pp. 175–179, May–June, 1993.     

Effects of extremely high-frequency electromagnetic radiation on the immune system and systemic regulation of homeostasis

Low-intensity of electromagnetic radiation of extremely high frequencies (EHF EMR) is effectively used in medical practice for diagnostics, prevention and treatment of a broad spectrum of diseases of different etiology. However, in spite of existence of many hypotheses about mechanisms of EHF EMR effects on the molecular and cellular levels of organization of living systems, there is not conception that could explain all diversity of the EHF-therapy effects from unified approach. In our opinion, the problem of determination of mechanisms of EHF EMR effects on living organism is divided into two basic tasks: first, determining subcellular structures which can receive radiation, and, second, studying physiological reactions of the organism which are caused by radiation. It is obviously, that investigation of functions of single cells and subcellular elements can not entirely explain therapeutic effects and mechanisms of EHF EMR influence on multicellular organism on the whole. Plenty of functional relationships between organs and systems of organs should be taken into account. In the present review, a realization of the EHF-therapy effects due to the influence on immune system functions and start of system mechanisms of maintenance of the homeostasis on the organism level is hypothesized. Potential targets for EHF EMR acception on the level of different systems of the organism are analysed. The material is formed so that functional relations between immune system and other regulatory systems (nervous and endocrine systems) are traced.     

Model analysis of nonlinear modification of neutrophil calcium homeostasis under the influence of modulated electromagnetic radiation of extremely high frequencies

The problem of resonance effects of electromagnetic radiation (EMR) on biological objects remained unsolved till now. Previously we demonstrated that low-intensity amplitude-modulated EMR of extremely high frequencies (EHF) modified the activity of mouse neutrophils in the synergistic reaction of calcium ionophore A23187 and phorbol ester PMA. The EHF EMR influence on the neutrophils was significant at the carrier frequencies of radiation within a narrow range of 41.8–42.05 GHz and at the modulation frequency of 1 Hz. The purpose of the work was the analysis of frequency-dependent modification of intracellular free calcium concentration ([Ca²⁺]_i) by modulated EHF EMR on the basis of a special model for [Ca²⁺]_i oscillations in the neutrophils. The calcium channels of plasma membrane were chosen as the action target of external modulation in the model. The computer simulation demonstrated the rise in [Ca²⁺]_i at the influence of the external field with a threshold dependence on the modulation amplitude. The effect depended heavily on a sequence of delivery of the chemical and electromagnetic stimuli. The narrow-band rise in [Ca²⁺]_i had a phase-frequency dependence. With the modulation amplitudes exceeding the threshold value, the rise in [Ca²⁺]_i of more than 50% of the initial level was observed at the frequency of about 1 Hz and in the phase range of 0.3–2.5 radians. The results of the model analysis are in good correspondence with the experimental data obtained before, namely, with the resonance modification of the neutrophil activity at the modulation frequency of 1 Hz and with the presence of the effect only at high concentrations of calcium ionophore.     

Hypokinetic stress-induced modifications of the pain sensitivity in rats

We examined the modifying effect of hypokinetic stress on the duration of behavioral phenomena in rats under conditions of experimentally induced tonic somatic, visceral, acute thermal, and electrostimulation-evoked pain. Stress of the above type (hypokinetic) was found to modify the pain sensitivity in rats related to all tested types of pain stresses of different etiology. Changes in the pain sensitivity of the animals under conditions of experimental pain tests depended on the duration of mobility restriction and could demonstrate opposite directions. Neirofiziologiya/Neurophysiology, Vol. 39, No. 2, pp. 174–183, March–April, 2007.     

Hydrogen peroxide induced by modulated electromagnetic radiation protects the cells from DNA damage

It is believed that non-ionizing electromagnetic radiation (EMR) and low-level hydrogen peroxide (H₂O₂) may change nonspecific resistance and modify DNA damage caused by ionizing radiation. To check this assumption, the combined effects of extremely high-frequency EMR (EHF EMR) and X-rays on induction of DNA damage in mouse whole blood leukocytes were studied. The cells were exposed to X-rays with or without preliminary treatment with EHF EMR or low-level H₂O₂. With the use of enhanced chemiluminescence, it was shown for the first time that pulse-modulated EHF EMR (42.2 GHz, incident power density of 0.1 mW/cm², exposure duration of 20 min, modulation frequency of 1 Hz) induced H₂O₂ at a concentration of 4.6 ± 0.3 nM L^?1 in physiological saline. With the use of an alkaline comet assay, it was found that the exposure of cells to the pulse-modulated EHF EMR, 25 min prior to treatment with X-rays at a dose of 4 Gy reduced the level of ionizing radiation-induced DNA damage. Continuous EHF EMR was inefficient. In turn, it was shown that low-level H₂O₂ (30–500 nM L^?1) protected the cells against X-irradiation. Thus, the mechanisms of radiation protective effect of EHF EMR are connected with the induction of the adaptive response by nanomolar concentrations of reactive oxygen species formed by pulse-modulated EHF EMR.     

Environmental stress of mobile phone EM radiation on locomotor activity and melatonin circadian rhythms of rats

Biological clocks are innate timing mechanisms that regulate many behavioral and physiological parameters in most organisms. In our modern life, heavy use of mobile phones (MPs) exerts a massive stress on organisms because their electromagnetic radiation usually results in varying degrees of damage to their biological systems including the biological rhythms. In the present study, the possible effects of exposure to radiofrequency–electromagnetic radiation (RF–EMR) from MPs on two characteristic circadian rhythms, locomotor activity and melatonin hormone rhythms, were investigated. Rats were exposed to RF–EMR from MPs at 900 MHz frequency (2-h/day for 2 weeks) during nighttime (20:00–22:00 h) followed by another two weeks without exposure for recovery. Locomotor activity rhythms of the control and treated groups (n = 5/group) were daily recorded using running wheels along the experimental period. For evaluating melatonin hormone rhythm, blood samples of control and treated groups (n = 12/group), were collected at the end of exposure and recovery periods, at 6-h time intervals per day (at 4:00, 10:00, 16:00, and 22:00 h). Rats exposed to RF–EMR exhibited phase shifting as well as a significant increased acrophase level in locomotor activity. Meanwhile, a significant decrease in serum melatonin levels with retaining lower amplitude rhythmicity was observed. Ceasing exposure for two weeks did not restore melatonin levels and circadian locomotor activity rhythms. It could be concluded that, under the current conditions, exposure to RF–EMR revealed disturbances in locomotor activity and melatonin level, although they maintained rhythmicity.     

Pharmacological analysis of the antiinflammatory effects of low-intensity extremely-high-frequency electromagnetic radiation

The antiinflammatory effect of low-intensity extremely-high-frequency electromagnetic radiation (EHF EMR, 42.0 GHz, 0.1 mW/cm²) was studied in comparison to the effects of the antiinflammatory drug sodium diclofenac and the antihistamine clemastine in acute inflammatory reaction in mice of NMRI outbred stock. The local inflammatory reaction was induced by intraplantar injection of zymosan to the left hind paw. Intraperitoneal injections of 2, 3, 5, 10, and 20 mg/kg of sodium diclofenac or 0.02, 0.1, 0.2, 0.4, and 0.6 mg/kg of clemastine were made 30 min after the initiation of inflammation. An hour after the initiation of inflammation, animals were whole-body exposed to EHF EMR for 20 min. The inflammatory reaction was assessed 3–8 h after initiation by measuring the footpad edema and hyperthermia of the inflamed paw. Sodium diclofenac (5–20 mg/kg) reduced the exudative edema by ～26% compared to the control. Hyperthermia of the inflamed paw decreased by 60% with an increase in the diclofenac dose to 20 mg/kg. EHF EMR reduced both the footpad edema and hyperthermia by ～20%. This was comparable to the effect of a single therapeutic dose of diclofenac (3–5 mg/kg). The combination of diclofenac and exposure to EHF EMR produced a partial additive effect. Clemastine (0.02–0.4 mg/kg) did not affect the exudative edema, but at a dose of 0.6 mg/kg, edema was reduced by 14–22% five to eight hours after zymosan injection. Clemastine caused a dose-dependent increase in hyperthermia of inflamed paw at doses 0.02–0.2 mg/kg and did not affect the hyperthermia at doses 0.4 and 0.6 mg/kg. A combination of clemastine and EHF EMR exposure resulted in a dose-dependent abolishment of the antiinflammatory effect of EHF EMR. Our results suggest that both arachidonic acid metabolites and histamine are involved in the achievement of the antiinflammatory effects of low-intensity EHF EMR.     

Features of anti‐inflammatory effects of modulated extremely high‐frequency electromagnetic radiation

Using a model of acute zymosan‐induced paw edema in NMRI mice, we test the hypothesis that anti‐inflammatory effects of extremely high‐frequency electromagnetic radiation (EHF EMR) can be essentially modified by application of pulse modulation with certain frequencies. It has been revealed that a single exposure of animals to continuous EHF EMR for 20 min reduced the exudative edema of inflamed paw on average by 19% at intensities of 0.1–0.7 mW/cm² and frequencies from the range of 42.2–42.6 GHz. At fixed effective carrier frequency of 42.2 GHz, the anti‐inflammatory effect of EHF EMR did not depend on modulation frequencies, that is, application of different modulation frequencies from the range of 0.03–100 Hz did not lead to considerable changes in the effect level. On the contrary, at “ineffective” carrier frequencies of 43.0 and 61.22 GHz, the use of modulation frequencies of 0.07–0.1 and 20–30 Hz has allowed us to restore the effect up to a maximal level. The results obtained show the critical dependence of anti‐inflammatory action of low‐intensity EHF EMR on carrier and modulation frequencies. Within the framework of this study, the possibility of changing the level of expected biological effect of modulated EMR by a special selection of combination of carrier and modulation frequencies is confirmed. Bioelectromagnetics 30:454–461, 2009. © 2009 Wiley‐Liss, Inc.     

Melatonin attenuates the acetylcholine-induced contraction in isolated intestine of a teleost fish

The present study investigates the possible direct actions of melatonin (N-acetyl-5-methoxytryptamine) on intestinal motility in goldfish (Carassius auratus) using an in vitro system of isolated intestine in an organ bath engaged to an isometric transducer. The longitudinal strips from goldfish intestine in the organ bath showed a resting spontaneous myogenic rhythmic activity which is not altered by melatonin. The addition of acetylcholine (1 nmol l⁻¹–10 mmol l⁻¹) to the organ bath induces a significant contraction of the intestinal strips in a concentration-dependent manner. The addition of melatonin and its agonist, 2-iodomelatonin, induced a concentration-dependent attenuation of acetylcholine-induced contractile response. The specificity of this effect is tested by the preincubation of the intestine strips in the presence of two melatoninergic antagonists, luzindole (a non-selective MT₁/MT₂ melatonin receptor antagonist) and 4-P-PDOT (preferred antagonist of MT2 receptor subtype), which counteracted the melatonin-induced relaxation in a concentration-dependent manner. Finally, present results demonstrate that this melatoninergic effect on intestinal strips is a process highly dependent on extracellular calcium. In conclusion, this is the first study demonstrating the role of melatonin in the control of gut motility in a non-mammalian vertebrate. The melatonin effects on isolated intestine from goldfish are mediated by melatoninergic membrane receptors, and could suggest a delay in food transit time, supporting its anorectic effect reported on in vivo studies.     

Effects of low-intensity extremely high frequency electromagnetic radiation on chromatin structure of lymphoid cells in vivo and in vitro

Using a comet assay technique, it was shown for the first time that low-intensity extremely high-frequency electromagnetic radiation (EHF EMR) in vivo causes oppositely directed effects on spatial organization of chromatin in cells of lymphoid organs. In 3 hrs after single whole-body exposure of NMRI mice for 20 min at 42.0 GHz and 0.15 mW/cm2, an increase by 16% (p < 0.03 as compared with control) and a decrease by 16% (p < 0.001) in fluorescence intensity of nucleoids stained with ethidium bromide were found in thymocytes and splenocytes, respectively. The fluorescence intensity of stained nucleoids in peripheral blood leukocytes was not changed after the exposure. The exposure of cells of Raji hunan lymphoid line and peripheral blood leukocytes to the EHF EMR in vitro induced a decrease in fluorescence intensity by 23% (p < 0.001) and 18% (p < 0.05), respectively. These effects can be determined by changes in a number of physiological alkali-labile sites in DNA of exposed cells. We suggested that the effects of low-intensity EHF EMR on the immune system cells are realized with the participation of neuroendocrine and central nervous systems.