The effects of extremely low-frequency pulsed electromagnetic fields on analgesia in the nitric oxide pathway.

There is growing interest in the effects of extremely low-frequency electromagnetic fields on mechanisms in biological organisms. This study's goal is to determine the role of the Nitiric Oxide (NO) pathway for thermal pain by intentionally interfering with it using a pulsed electromagnetic field generated by an extremely low-frequency alternating current (ELF-PEMF) in combination with BAY41-2272 (sGC activator), NOS inhibitor l-NAME, and NO donor l-arginine. This study included 72 adult male Wistar albino rats (mean weight of 230 ±â€¯12 g). The rats were kept at room temperature (22 ±â€¯2 °C) in a 12-h light/dark cycle and in a room with sound insulation. PEMF (50 Hz, 5 mT) were applied four times a day for 30 min and at 15-min intervals for 15 days. Analgesic effects were assessed with tail-flick and hot-plate tests. Before the tests, NO donor l-arginine (300 mg/kg), sGC activator BAY41-2272 (10 mg/kg), and NOS inhibitor l-name (40 mg/kg) were injected intraperitoneally into rats in six randomly-selected groups. The maximum analgesic effect of a 5 mT electromagnetic field was on day 7. PEMF significantly increased the analgesia effect when the functioning of the NO pathway was ensured with l-arginine, which is a NO donor, and BAY41-2271, which is the intracellular receptor and sGC activator. However, there was no difference between rats treated with PEMF and the NOS inhibitor l-NAME as compared to rats only treated with PEMF. In conclusion, PEMF generate analgesia by activating the NO pain pathway.

Effects of 5-HT1 and 5-HT 2 Receptor Agonists on Electromagnetic Field-Induced Analgesia in Rats.

Much evidence demonstrates the antinociceptive effect of magnetic fields (MFs). However, the analgesic action mechanism of the electromagnetic field (EMF) is not exactly understood. The aim of the present study was to investigate the effects of 5-HT1 and 5-HT2 receptor agonists (serotonin HCl and 2,5-dimethoxy-4-iodoamphetamine [DOI] hydrochloride) on EMF-induced analgesia. In total, 66 adult male Wistar albino rats with an average body mass of 225 ± 13 g were used in this study. The animals were subjected to repeated exposures of alternating 50 Hz and 5 mT EMF for 2 h a day for 15 days. Prior to analgesia tests, serotonin HCl (5-HT1 agonist) 4 mg/kg, WAY 100635 (5-HT1 antagonist) 0.04 mg/kg, DOI hydrochloride (5-HT2 receptor agonist) 4 mg/kg, and SB 204741 (5-HT2 antagonist) 0.5 mg/kg doses were injected into rats. For statistical analysis of the data, analysis of variance was used and multiple comparisons were determined by Tukey's test. Administration of serotonin HCl MF (5 mT)-exposed rats produced a significant increase in percent maximal possible effect (% MPE) as compared with EMF group (P < 0.05). On the contrary, injection of WAY 100635 to MF-exposed rats produced a significant decrease in analgesic activity (P < 0.05). Similarly, the administration of DOI hydrochloride significantly increased % MPE values as compared with the EMF group while SB 204741 reduced it (P < 0.05). In conclusion, our results suggested that serotonin 5-HT1 and 5-HT2 receptors play an important role in EMF-induced analgesia; however, further research studies are necessary to understand the mechanism. Bioelectromagnetics. 2019;40:319-330. © 2019 Bioelectromagnetics Society.

Effects of extremely low frequency electromagnetic fields on morphine analgesia and tolerance in rats.

Several studies have demonstrated that the electromagnetic fields produce analgesic activity. The aim of this study was to investigate the effects of extremely low frequency (ELF) electromagnetic fields (EMF) on morphine analgesia and tolerance in rats. In the study, 78 adult male Wistar albino rats (approximately 240 ± 12 g) were used. The application of 50 Hz magnetic field, each day the same times for 30 minutes for 15 days, and a total of four times every 15 minute intervals. To constitute morphine tolerance, high dose of morphine (50 mg/kg) were administered for 3 days in rats and tolerance was evaluated on day 4. Prior to analgesia tests, the effective dose (5 mg/kg) of morphine was injected into rats. In the statistical analyzes of the data, analysis of variance (two-way ANOVA) was used and the multiple comparison determined by Tukey tests. The maximum analgesic effect of the 5 mT magnetic field was determined on 7 days. Administration of morphine (5 mg/kg) in rats exposed to a magnetic field, the analgesic effect was significantly higher compared to the morphine group (p < 0.05). Morphine tolerant animals exposed to a magnetic field, the analgesic effect was found significantly higher than morphine tolerant group rats (p < 0.05). Analgesia test data demonstrated that application of ELF-EMFs to rats increases the morphine analgesia and reduces morphine tolerance.

Effect of exposure to 50 Hz magnetic field with or without insulin on blood-brain barrier permeability in streptozotocin-induced diabetic rats.

We investigated the effect of long-term exposure to modulation magnetic field (MF), insulin, and their combination on blood-brain barrier (BBB) permeability in a diabetic rat model. Fifty-three rats were randomly assigned to one of six groups: sham, exposed to no MF; MF, exposed to MF; diabetes mellitus (DM), DM induced with streptozotocin (STZ); DM plus MF (DMMF); DM plus insulin therapy (DMI); and DM plus insulin therapy plus MF (DMIMF). All the rats underwent Evans blue (EB) measurement to evaluate the BBB 30 days after the beginning of experiments. The rats in MF, DMMF, and DMIMF groups were exposed to MF (B = 5 mT) for 165 min every day for 30 days. Mean arterial blood pressure (MABP), body mass, and serum glucose level of the study rats were recorded. The extravasation of brain EB of the MF, DM, DMMF, DMI, and DMIMF groups was higher than that of the sham group and the extravasation of right hemisphere of the DMIMF group was highest (P < 0.05). The post-procedure body mass of the sham and MF groups were significantly higher than those of the DM and DMMF groups (P < 0.05). In the DM, DMMF, DMI, and DMIMF groups, the baseline glucose was significantly lower than the post-procedure glucose (P < 0.05). DM and MF increase BBB permeability; in combination, they cause more increase in BBB permeability, and insulin decreases their effect on BBB. Improved glucose metabolism may prevent body mass loss and the hypoglycemic effect of MF. DM increases MABP but MF causes no additional effect.

Repetitive 50 Hz pulsed electromagnetic field ameliorates the diabetes-induced impairments in the relaxation response of rat thoracic aorta rings.

PURPOSE: To evaluate the characteristic features of mechanical responses and the membrane potential changes induced by repetitive pulsed electromagnetic field (PEMF, 50 Hz, 5 mT) in thoracic aorta rings obtained from streptozotocin-induced diabetic and healthy control rats to determine if PEMF could ameliorate problems associated with diabetes. METHODS: Sixty male Wistar rats weighing 250-290 g were randomly divided into two experimental groups, each containing 30 animals. Streptozotocin was given via tail vein to produce diabetes mellitus (DM) in the first group rats. The second group rats were treated only with % 0.9 saline and considered as non-DM group. Both groups were also divided into two subgroups as DM + PEMF, DM + sham, PEMF and sham, each containing 15 animals. Although the DM + PEMF and PEMF groups were treated, the DM + sham and sham groups were not treated with PEMF. The PEMF treatment occurred four times daily for 30 min at 15-min intervals repeated daily for 30 days. Thoracic aorta rings from both DM and non-DM rats exposed to PEMF were evaluated for contraction and relaxation responses and membrane potential changes in the presence or absence of chemical agents that were selected to test various modes of action. RESULTS: Relaxation response of thoracic aorta rings was significantly reduced in DM than non-DM group. PEMF treatment significantly increased the relaxation response of the diabetic rings to acetylcholine, and reduced the concentration response to phenylephrine. Resting membrane potential was significantly higher in DM than in non-DM group. Inhibitors of nitric oxide (NO), both nitro-L-arginine (L-NO-ARG) and L-NO-ARG + indometacin combination, produced a significant transient hyperpolarisation in all groups. Inhibitors of potassium channel activity, charybdotoxin or apamine, produced a membrane depolarisation. However, PEMF did not induce any significant effect on the membrane potential in DM group. CONCLUSIONS: Diabetes reduced the relaxation response of thoracic aorta rings. It also affected the membrane potentials of the rings. Treatment with PEMF ameliorated the diabetes-induced impairments in the relaxation response of these rings.

Delayed habituation in Behcet's disease.

BACKGROUND: The autonomic nervous system in Behcet's patients may be affected due to various reasons. This entity may be detected with the measurement of the electrodermal activities, heart rate variability and pupillometric methods. Habituation is one of the implicit forms of learning and memory and the loss of habituation can reveal pathological changes in the synaptic regions. AIM: To determine whether there is a functional decrease in the synaptic effectiveness (habituation) of the pathways to sympathetic neurons that had been repeatedly activated in Behcet's. MATERIALS AND METHODS: Twelve patients with Behcet's disease and 12 healthy controls were included in the study. Sympathetic skin potential (SSP) records were taken at normal room temperature in a quiet place within a Faraday cage. Sixteen square wave single shock impulses (duration: 1200 ms, strength: 5 mA) were applied on each case. RESULTS: After the 1st stimulus, the SSP amplitudes were lower in the patients compared to the controls (P<0.001, t value=7.69). There was no significant differences among the SSP amplitudes after the 13th impulse in the patients (P>0.05). Whereas there was no significant differences among the SSP amplitudes after the 9th impulse in the controls (P>0.05). The habituation rate of the SSP after consecutive impulses was slowest in the patients compared to controls (P<0.001, t value=12.39). CONCLUSIONS: There is a delayed habituation in Behcet's disease and that may due to pathologic changes with vasculitis through their peripheral nerves.

Polymorphisms in the tumor necrosis factor-alpha gene in Turkish women with pre-eclampsia and eclampsia.

The genetic background predisposing pregnant women to pre-eclampsia/eclampsia (PE/E) is still unknown. The aim of the current study was to investigate whether there is an association between the TNF-alpha-308 and 850 polymorphisms and PE or eclampsia. In this study, 40 cases of eclampsia, 113 cases of PE and 80 normotensive control cases were genotyped for the TNF-alpha-G-308A and C-850 polymorphisms. At position 308, the replacement of Guanine with Adenosine was denoted as TNF2. We found a significant difference between the TNF2 allele frequencies of the eclamptic, pre-eclamptic and normotensive controls. TNF2 (AA) polymorphism frequency was significantly higher among the eclamptics and pre-eclamptics (control : 5%, PE : 13.3%, E : 12.9%). A significantly different genotype distribution of C-850T polymorphism was observed between the PE/E and control groups, with the frequency of the variant TT genotype being significantly reduced in the preeclamptics (PE : 17% ; E : 17.5%) when compared with the control group (24.3%). We have demonstrated an association between TNF-alpha polymorphisms and pre-eclampsia susceptibility. However, it is not known whether C-850T polymorphism has a functional effect on the TNF-alpha gene. In addition, it was not possible to determine whether this polymorphism promotes the progression from PE to eclampsia because of no statistically significant difference between eclampsia and the controls.

The acute effect of trimetazidine on the high frequency fatigue in the isolated rat diaphragm muscle.

The objective of this study was to determine the acute effect of trimetazidine (TMZ) on the pre-fatigue, fatigue and post-fatigue contractile characteristics and tension-frequency relationships of isolated rat diaphragm muscle. Muscle strips were taken from the ventral-costal aspects of the diaphragm muscle of rats killed by decapitation. The muscle strips were suspended in organ baths containing Krebs solution, with a gas mixture of 95% O2 and 5% CO2 at 37 degrees C and pH 7.35-7.45. After determining the thermoregulation and optimum muscle length the muscles were subjected to direct supramaximal stimulation with 0.05 Hz frequency square pulses for periods of 0.5 msec to obtain control values. After adding 5 x 10(-6) and 5 x 10(-5) M trimetazidine solution to the respective bath media, the contractile parameters of the muscles were recorded. The contractile parameters were also recorded for both the trimetazidine and trimetazidine-free media after application of the high frequency fatigue protocols. Later, the tension-frequency relationship was determined by applying stimulating pulses of 10, 20, 50 and 100 Hz to the muscle strips. Whilst the twitch tension obtained from the 5 x 10(-6) and 5 x 10(-5) M trimetazidine media showed numerical increases compared to that of the controls, these were not statistically significant (p>0.05). The contraction time exhibited a dose dependent increase (p<0.001), whilst the contraction and relaxation rates did not differ significantly. The isometric contraction forces obtained with the different stimulating frequencies showed a significant increase in the tetanic contraction only at 100 Hz (p<0.05). A comparison of the pre- and post-fatigue twitch tensions in the trimetazidine media showed the post- fatigue twitch tensions to be significantly higher than those of the pre-fatigue contraction forces (p<0.05). In the 5 x 10(-6) and 5 x 10(-5) M trimetazidine media the increases in the post-fatigue contraction force were 22 and 30%, respectively. These results demonstrated that in isolated rat diaphragm muscle, TMZ significantly limited the mechanical performance decrease during fatigue. It is our opinion that trimetazidine contributed to the observed fatigue tolerance by eliminating the factors of fatigue, due to preservation of intracellular calcium homeostasis, provision of the ATP energy levels needed by ATPase dependent pumps and especially by keeping the intracellular pH within certain limits.