Lateral gradients significantly enhance static magnetic field-induced inhibition of pain responses in mice--a double blind experimental study.

Recent research demonstrated that exposure of mice to both inhomogeneous (3-477 mT) and homogeneous (145 mT) static magnetic fields (SMF) generated an analgesic effect toward visceral pain elicited by the intraperitoneal injection of 0.6% acetic acid. In the present work, we investigated behavioral responses such as writhing, entry avoidance, and site preference with the help of a specially designed cage that partially protruded into either the homogeneous (ho) or inhomogeneous (inh) SMF. Aversive effects, cognitive recognition of analgesia, and social behavior governed mice in their free locomotion between SMF and sham sides. The inhibition of pain response (I) for the 0-5, 6-20, and 21-30 min periods following the challenge was calculated by the formula I = 100 (1 - x/y) in %, where x and y represent the number of writhings in the SMF and sham sides, respectively. In accordance with previous measurements, an analgesic effect was induced in exposed mice (Iho = 64%, P < 0.0002 and Iinh = 62%, P < 0.002). No significant difference was found in the site preference (SMFho, inh vs. sham) indicating that SMF is neither aversive nor favorable. Comparison of writhings observed in the sham versus SMF side of the cage revealed that SMF exposure resulted in significantly fewer writhings than sham (Iho = 64%, P < 0.004 and Iinh = 81%, P < 0.03). Deeper statistical analysis clarified that the lateral SMF gradient between SMF and sham sides could be responsible for most of the analgesic effect (Iho = 91%, P < 0.02 and Iinh = 54%, P < 0.02).

Exposure to static magnetic field delays induced preterm birth occurrence in mice.

OBJECTIVE: The purpose of this study was to demonstrate that daily 40-minute whole body exposure to an inhomogeneous static magnetic field (SMF) prolongs induced preterm birth (PTB) in mice. STUDY DESIGN: The murine model for PTB induction was performed by the administration of 25 µg/animal lipopolysaccharide (LPS) intraperitoneally. The applied SMF was an inhomogeneous gradient field with 2.8-476.7 millitesla peak-to-peak magnetic induction range by 10 mm lateral periodicity. During SMF exposure, mice were free to move in their cage. RESULTS: The fetal development and the delivery were normal in animals that were exposed to SMF but not treated with LPS. SMF in these cases did not influence the term of delivery. In LPS-challenged animals, SMF exposure prolonged the time of PTB occurrence from 17.43 h (n = 7) to 21.93 h (n = 15) after the challenge (P < .05). CONCLUSION: Exposure to inhomogeneous SMF may have a valuable effect in the prevention of PTB and may have clinical relevance to humans.

Exposure to an inhomogeneous static magnetic field increases thermal pain threshold in healthy human volunteers.

In the present experiment, the effect of a single 30 min inhomogeneous static magnetic field (SMF) exposure on thermal pain threshold (TPT) was examined in 15 young healthy human volunteers. The SMF had a maximum peak-to-peak amplitude of 330 mT with a maximum gradient of 13.2 T/m. In either of two experimental sessions (SMF or SHAM), four blocks of 12 TPT trials were carried out under SMF or SHAM exposure on all fingertips of the dominant hand, excluding the thumb. TPT and visual analog scale (VAS) data were recorded at 0, 15, and 30 min exposure time, and 30 min following exposure. SMF treatment resulted in a statistically significant increase in TPT during the entire exposure duration and diminished within-block thermal habituation, leaving pain perception unchanged. These results indicate that SMF-induced peripheral neuronal or circulatory mechanisms may be involved in the observed TPT increase by setting the pain fibre adaptation potential to higher levels.

Static magnetic field exposure in 1.5 and 3 Tesla MR scanners does not influence pain and touch perception in healthy volunteers.

BACKGROUND: Magnetic field therapy is a popular approach to pain therapy, but scientific evidence on treatment effects or even effects on sensory and pain perception in healthy controls is scarce. METHODS: In the present randomized, placebo-controlled study, we investigated the influence of static magnetic field exposure on sensory (touch) and pain (pinprick, pressure and heat) perception. Eighteen healthy volunteers (age: 23 ± 2 years, nine women) underwent three 10-min static magnetic field exposures using field strengths of 0 T (placebo), 1.5 T and 3 T within clinical MR scanners in randomized order on three separate days. Participants were blinded to magnetic field strength. Experimental sensory and pain testing was performed immediately before and after each magnetic field exposure. RESULTS: There was no significant effect of field strength on the assessed experimental sensory and pain testing parameters (mechanical detection threshold, pinprick threshold, pressure pain threshold, heat pain threshold and suprathreshold heat pain rating). CONCLUSION: We found no evidence that a 10-min 1.5 T or 3 T static magnetic field exposure affects experimental sensory or pain perception in young healthy volunteers. SIGNIFICANCE: We used clinical MR scanners to investigate the effect of magnetic fields on pain perception. Using a rigorous, straightforward, placebo-controlled design, no effect of static magnetic fields on human experimental pain perception was detected. This provides a base for a more systematic investigation of magnetic field effects on pain.

Analysis of the effect of locally applied inhomogeneous static magnetic field-exposure on mouse ear edema--a double blind study.

The effect static magnetic field (SMF)-exposure may exert on edema development has been investigated. A 6 h long whole-body (WBSMF) or local (LSMF), continuous, inhomogeneous SMF-exposure was applied on anesthetized mice in an in vivo model of mustard oil (MO)-induced ear edema. LSMF was applied below the treated ear, below the lumbar spine, or below the mandible. Ear thickness (v) was checked 8 times during the exposure period (at 0, 0.25, 1, 2, 3, 4, 5, and 6 h). The effect size of the applied treatment (η) on ear thickness was calculated by the formula η = 100% × (1-v(j)/v(i)), where group i is the control group and j is the treated group. Results showed that MO treatment in itself induced a significant ear edema with an effect of 9% (p<0.001). WBSMF or LSMF on the spine in combination with MO treatment increased ear thickness even further resulting in an effect of η>11% in both cases compared to SMF-exposure alone (p<0.001). In these cases SMF-exposure alone without MO treatment reduced ear thickness significantly (p<0.05), but within estimated experimental error. In cases of LSMF-exposure on the head, a significant SMF-exposure induced ear thickness reduction was found (η = 5%, p<0.05). LSMF-exposure on the spine affected ear thickness with and without MO treatment almost identically, which provides evidence that the place of local SMF action may be in the lower spinal region.

Pharmacological analysis of response latency in the hot plate test following whole-body static magnetic field-exposure in the snail Helix pomatia.

PURPOSE: To study the effect of single, 30-min long, whole-body, homogeneous static magnetic field (SMF)-exposure of magnetic induction 147 ± 3 mT on the response latency of the snail Helix pomatia. MATERIALS AND METHODS: The response was investigated using the hot plate test. RESULTS: The effect caused by exposure to SMF was compared to sham-exposure and resulted in significant differences (up to 47.1%, p < 0.001). The response latency depended on the day-night cycle; response latency was higher by 51.2% (p < 0.001) during the night. This trend also held for SMF-exposure (28.6%, p < 0.001). Serotonin alone increased response latency (55.7%, p < 0.001), whereas serotonin antagonist tryptamine decreased it (- 97.8%, p < 0.001). Using naloxone, response latency decreased (- 52.5%, p < 0.001); however both SMF-exposure and serotonin in combination with naloxone rose it back to above the control level (116.9%, p < 0.001 or 150.2%, p < 0.001, respectively). CONCLUSIONS: This study provides evidence that SMF-exposure mediates peripheral thermal nociceptive threshold by affecting the serotonerg as well as the opioiderg system.

The effect of whole-body, repetitive, inhomogeneous static magnetic field-exposure on the symptoms of experimental autoimmune encephalomyelitis in mice.

Experimental autoimmune encephalomyelitis (EAE) is a model for human multiple sclerosis (MS) in rodents. Static magnetic field (SMF)-exposure was shown to be beneficial in specific cases of inflammatory background, where it suppresses symptoms. The null-hypothesis was that animals with induced EAE exposed to SMF would show different seriousness of symptoms, than those in the sham-exposed control group. Three replicated series of repetitive, 30 min/day whole-body exposure to SMF with 477 mT peak-to-peak magnetic induction and 48 T/m lateral induction gradient was tested on female CSJLF1 mice with a mild, mouse spinal cord homogenate emulsion-induced EAE. Conventional scores of the animal response to EAE were compared between sham- and SMF-exposed groups of animals. Following pilot test we used 18 animals per group. Primary outcome measure was the daily group average of standard EAE scores. Results show that SMF-exposure has a strong, reproducible, and significantly beneficial effect up to 51.82% (p<0.001) over sham-exposure on the symptoms of EAE in the course of the 25 days of the experiment. This study aimed to build experimental research foundation for a later therapy option by applying SMF-exposure in the clinical management of MS.

Influence of inhomogeneous static magnetic field-exposure on patients with erosive gastritis: a randomized, self- and placebo-controlled, double-blind, single centre, pilot study.

This pilot study was devoted to the effect of static magnetic field (SMF)-exposure on erosive gastritis. The randomized, self- and placebo-controlled, double-blind, pilot study included 16 patients of the 2nd Department of Internal Medicine, Semmelweis University diagnosed with erosive gastritis. The instrumental analysis followed a qualitative (pre-intervention) assessment of the symptoms by the patient: lower heartburn (in the ventricle), upper heartburn (in the oesophagus), epigastric pain, regurgitation, bloating and dry cough. Medical diagnosis included a double-line upper panendoscopy followed by 30 min local inhomogeneous SMF-exposure intervention at the lower sternal region over the stomach with peak-to-peak magnetic induction of 3 mT and 30 mT m(-1) gradient at the target site. A qualitative (post-intervention) assessment of the same symptoms closed the examination. Sham- or SMF-exposure was used in a double-blind manner. The authors succeeded in justifying the clinically and statistically significant beneficial effect of the SMF- over sham-exposure on the symptoms of erosive gastritis, the average effect of inhibition was 56% by p = 0.001, n = 42 + 96. This pilot study was aimed to encourage gastroenterologists to test local, inhomogeneous SMF-exposure on erosive gastritis patients, so this intervention may become an evidence-based alternative or complementary method in the clinical use especially in cases when conventional therapy options are contraindicated.

Analgesic and anti-inflammatory effectiveness of sitagliptin and vildagliptin in mice.

To validate the potential anti-inflammatory and analgesic role of sita- and vildagliptin, five different experimental models were used in mice: i) mustard oil-induced ear edema, ii) neutrophil accumulation, iii) mechanical and iv) thermal touch sensitivity in complete Freund's adjuvant-induced arthritis and v) capsaicin-induced plasma extravasation in the urinary bladder. For the complete examination period in i) the dose of 10mg sitagliptin as well as 1-10mg vildagliptin was found to significantly decrease ear edema as compared to positive control (p<0.05, n=8/group). All doses of sitagliptin provided an anti-inflammatory effect p<0.005 (n=10/group) in test ii) and an analgesic effect in iii) except 3mg. Vildagliptin was similarly effective in test ii) (p<0.005, n=10/group) as sitagliptin, but it failed to affect mechanical touch sensitivity. Unlike mechanical touch sensitivity, both gliptins could beneficially act on the thermal threshold (p<0.05, n=10/group). And only in tests v) could both gliptins reverse inflammation. Further studies are needed to support the suggestion that the utilization of these beneficial effects of gliptins may be considered in the treatment of Type 2 diabetic patients.

Exposure to inhomogeneous static magnetic field beneficially affects allergic inflammation in a murine model.

Previous observations suggest that static magnetic field (SMF)-exposure acts on living organisms partly through reactive oxygen species (ROS) reactions. In this study, we aimed to define the impact of SMF-exposure on ragweed pollen extract (RWPE)-induced allergic inflammation closely associated with oxidative stress. Inhomogeneous SMF was generated with an apparatus validated previously providing a peak-to-peak magnetic induction of the dominant SMF component 389 mT by 39 T m(-1) lateral gradient in the in vivo and in vitro experiments, and 192 mT by 19 T m(-1) in the human study at the 3 mm target distance. Effects of SMF-exposure were studied in a murine model of allergic inflammation and also in human provoked skin allergy. We found that even a single 30-min exposure of mice to SMF immediately following intranasal RWPE challenge significantly lowered the increase in the total antioxidant capacity of the airways and decreased allergic inflammation. Repeated (on 3 consecutive days) or prolonged (60 min) exposure to SMF after RWPE challenge decreased the severity of allergic responses more efficiently than a single 30-min treatment. SMF-exposure did not alter ROS production by RWPE under cell-free conditions, while diminished RWPE-induced increase in the ROS levels in A549 epithelial cells. Results of the human skin prick tests indicated that SMF-exposure had no significant direct effect on provoked mast cell degranulation. The observed beneficial effects of SMF are likely owing to the mobilization of cellular ROS-eliminating mechanisms rather than direct modulation of ROS production by pollen NAD(P)H oxidases.

Risk of subsequent primary tumor development in melanoma patients.

Incidence of subsequent malignant tumor development in 740 patients with primary cutaneous melanoma verified between 2006 and 2010 at the Semmelweis University was studied retrospectively and was compared to data of sex and age matched Hungarian population. The follow-up period was 1499 person-years for the whole group from the diagnosis of index melanoma with an average of 2 years. Standardized incidence rate (SIR) was established as the ratio of observed and expected values. The risk of all subsequent malignancies was 15- and 10-fold higher in males (SIR: 15.42) and in females (SIR: 10.55) with melanoma, than in the general population. The increased cancer risk resulted mainly from the significantly higher skin tumor development: SIR values were 160.39 and 92.64 for additional invasive melanoma and 342.28 and 77.04 for subsequent in situ melanoma in males and females, respectively. Non-melanoma skin cancers also notably contributed to the higher risk, the SIR was elevated in both genders to the same extent (males: 17.12, females: 17.55). The risk was also significantly higher for extracutaneous tumor development like chronic lymphocytic leukemia, colon and kidney cancer (both genders), non-Hodgkin's lymphoma, cervical cancer (females), and bladder carcinoma (males). These data underline the importance of patient education and the necessity of frequent medical follow up, including a close-up dermatological screening of melanoma survivors for further malignancies.

Influence of local exposure to static magnetic field on pain perception and bone turnover of osteoporotic patients with vertebral deformity - a randomized controlled trial.

PURPOSE: Static magnetic field (SMF) could improve pain sensation and bone turnover. In a single-center randomized double-blind placebo-controlled study we investigated the effects of SMF exposure on subjective pain and bone turnover. MATERIALS AND METHODS: Postmenopausal osteoporotic women (aged 50-70 years) with bone deformity and back pain were randomized to 10 weekly visits of 30-min SMF (n = 6) or treatment with non-magnetized pads (n = 5) on the back. Primary and secondary outcomes were changes in pain sensation on a visual analogue scale (VAS) during each visit and over 10 weeks, respectively. Tertiary outcomes were changes in osteocalcin and ß-crosslaps. SMF was inhomogeneous with 192 millitesla peak-to-peak value by 19 tesla/meter gradient of the magnetic flux density at 3 mm. RESULTS: Participants randomized to sham had higher VAS at baseline (mean difference: 2.8, 95% confidence interval (CI) 0.47-5.2 cm). Both SMF and sham similarly reduced short term pain (sham-SMF: 0.59, 95% CI - 0.31-1.49 cm, p = 0.195). VAS did not change in SMF, while it decreased in the sham group (between-group difference 0.27, 95% CI 0.04-0.50 cm/visit). Bone turnover markers remained stable. CONCLUSIONS: SMF as used in this investigation is not recommended for pain relief in postmenopausal women with vertebral deformity. The finding on long-term pain relief may relate to unbalanced randomization.

In vitro analysis of the anti-inflammatory effect of inhomogeneous static magnetic field-exposure on human macrophages and lymphocytes.

The effect of inhomogeneous static magnetic field (SMF)-exposure on the production of different cytokines from human peripheral blood mononuclear cells (PMBC), i.e., lymphocytes and macrophages, was tested in vitro. Some cultures were activated with lipopolysaccharide (LPS) at time point -3 h and were either left alone (positive control) or exposed to SMF continuously from 0 until 6, 18, or 24 h. The secretion of interleukin IL-6, IL-8, tumor necrosis factor TNF-α, and IL-10 was tested by ELISA. SMF-exposure caused visible morphological changes on macrophages as well as on lymphocytes, and also seemed to be toxic to lymphocytes ([36.58; 41.52]%, 0.308≤p≤0.444), but not to macrophages (<1.43%, p≥0.987). Analysis of concentrations showed a significantly reduced production of pro-inflammatory cytokines IL-6, IL-8, and TNF-α from macrophages compared to negative control ([56.78; 87.52]%, p = 0.031) and IL-6 compared to positive control ([45.15; 56.03]%, p = 0.035). The production of anti-inflammatory cytokine IL-10 from macrophages and from lymphocytes was enhanced compared to negative control, significantly from lymphocytes ([-183.62; -28.75]%, p = 0.042). The secretion of IL-6 from lymphocytes was significantly decreased compared to positive control ([-115.15; -26.84]%, p = 0.039). This massive in vitro evidence supports the hypotheses that SMF-exposure (i) is harmful to lymphocytes in itself, (ii) suppresses the release of pro-inflammatory cytokines IL-6, IL-8, and TNF-α, and (iii) assists the production of anti-inflammatory cytokine IL-10; thus providing a background mechanism of the earlier in vivo demonstrated anti-inflammatory effects of SMF-exposure.

Effect of local exposure to inhomogeneous static magnetic field on stomatological pain sensation - a double-blind, randomized, placebo-controlled study.

PURPOSE: Static magnetic field (SMF) exposure was shown experimentally to beneficially affect the healing process. The aim of this randomized, controlled trial was to evaluate the pain-inhibitory effect of local exposure to SMF on temporomandibular disorders, on alveolitis and on aphta in the oral mucosa. MATERIALS AND METHODS: Pain perception was evaluated on the basis of ordinary visual analogue scale (VAS) testing before and after exposure. SMF (0-192 mT peak-to-peak magnetic induction and 19 T/m lateral gradient at 3 mm from the magnets) and sham exposure was executed in a double-blind manner. A single intervention took 5 min. Altogether 79 adult patients (22 males and 57 females) with a mean (± standard error of the mean) age of 37.4 ± 1.8 years (70.9% between 20 and 50 years) participated in the study. RESULTS: SMF exposure significantly reduced pain perception (reduction from baseline to post-treatment VAS score) in the group with temporomandibular disorders from 2.0 ± 0.3 to 0.5 ± 0.1 (n = 29, p = 0.0003), but not in case of the alveolitis, or the aphta group. CONCLUSIONS: SMF exposure as a drug-free, fast and easy to use method could potentially help stomatologists, who seek for alternative methods of local anesthesia, especially when systemic anesthesia is contraindicated.

Daily exposure to inhomogeneous static magnetic field significantly reduces blood glucose level in diabetic mice.

PURPOSE: The present study was designed to reveal, whether the 30 min daily full body exposure of mice to an inhomogeneous static magnetic field (SMF) has a statistically significant effect on diabetic neuropathy. MATERIALS AND METHODS: Three different doses (100, 150, or 200 mg/kg) of streptozotocin (STZ) were administered intraperitoneally in groups of mice to induce diabetes. Body weight, blood glucose level and the nociceptive temperature threshold of mice were monitored for a period of 12 weeks. The group treated with 200 mg/kg i.p. STZ produced manifest diabetic neuropathy. Results were compared to non-treated (no SMF, no STZ) and SMF exposure without STZ-treatment group (SMF, no STZ) group. The inhomogeneous SMF was in the range of 2.8-476.7 mT peak-to-peak magnetic flux density. RESULTS: Whereas SMF exposure did not seem to affect body weight and nociceptive temperature threshold, it statistically significantly (p < 0.001) reduced blood glucose level in the 200 mg/kg STZ (n = 6) group. CONCLUSIONS: Daily SMF exposure repeated for several weeks is protective against the development of high blood glucose level in diabetic mice.