Effect of 40 Hz Magnetic Field Application in Posttraumatic Muscular Atrophy Development on Muscle Mass and Contractions in Rats.

Muscle atrophy refers to the deterioration of muscle tissue due to a long-term decrease in muscle function. In the present study, we simulated rectus femoris muscle atrophy experimentally and investigated the effect of pulsed electromagnetic field (PEMF) application on the atrophy development through muscle mass, maximal contraction force, and contraction-relaxation time. A quadriceps tendon rupture with a total tenotomy was created on the rats' hind limbs, inhibiting knee extension for 6 weeks, and this restriction of the movement led to the development of disuse atrophy, while the control group underwent no surgery. The operated and control groups were divided into subgroups according to PEMF application (1.5 mT for 45 days) or no PEMF. All groups were sacrificed after 6 weeks and had their entire rectus femoris removed. To measure the contraction force, the muscles were placed in an organ bath connected to a transducer. As a result of the atrophy, muscle mass and strength were reduced in the operated group, while no muscle mass loss was observed in the operated PEMF group. Furthermore, measurements of single, incomplete and full tetanic contraction force and contraction time (CT) did not change significantly in the operated group that received the PEMF application. The PEMF application prevented atrophy resulting from 6 weeks of immobility, according to the contraction parameters. The effects of PEMF on contraction force and CT provide a basis for further studies in which PEMF is investigated as a noninvasive therapy for disuse atrophy development. © 2022 Bioelectromagnetics Society.

A Low-Frequency Pulsed Magnetic Field Reduces Neuropathic Pain by Regulating NaV1.8 and NaV1.9 Sodium Channels at the Transcriptional Level in Diabetic Rats.

Low-frequency pulsed magnetic field (LF-PMF) application is a non-invasive, easy, and inexpensive treatment method in pain management. However, the molecular mechanism underlying the effect of LF-PMF on pain is not fully understood. Considering the obvious dysregulations of gene expression observed in certain types of voltage-gated sodium channels (VGSCs) in pain conditions, the present study tested the hypothesis that LF-PMF shows its pain-relieving effect by regulating genes that code VGSCs proteins. Five experimental rat groups (Control, Streptozotocin-induced experimental painful diabetic neuropathy (PDN), PDN Sham, PDN 10 Hz PMF, and PDN 30 Hz PMF) were established. After the pain formation in PDN groups, the magnetic field groups were exposed to 10/30 Hz, 1.5 mT PMF for 4 weeks, an hour daily. Progression of pain was evaluated using behavioral pain tests during the entire experimental processes. After the end of PMF treatment, SCN9A (NaV1.7 ), SCN10A (NaV1.8 ), SCN11A (NaV1.9 ), and SCN3A (NaV1.3 ) gene expression level changes were determined by analyzing real-time polymerase chain reaction results. We found that 10 Hz PMF application was more effective than 30 Hz on pain management. In addition, NaV1.7 and NaV1.3 transcriptions were upregulated while NaV1.8 and NaV1.9 were downregulated in painful conditions. Notably, the downregulated expression of the genes encoding NaV1.8 and NaV1.9 were re-regulated and increased to control level by 10 Hz PMF application. Consequently, it may be deduced that 10 Hz PMF application reduces pain by modulating certain VGSCs at the transcriptional level. © 2021 Bioelectromagnetics Society.

Pulsed magnetic field enhances therapeutic efficiency of mesenchymal stem cells in chronic neuropathic pain model.

Cell-based or magnetic field therapies as alternative approaches to pain management have been tested in several experimental pain models. The aim of this study therefore was to investigate the actions of the cell-based therapy (adipose tissue derived mesenchymal stem cells; ADMSC) or pulsed magnetic field (PMF) therapy and magneto-cell therapy (combination of ADMSC and PMF) in chronic constriction nerve injury model (CCI). The actions of individual ADMSC (route dependent [systemic or local], time-dependent [a day or a week after surgery]), or PMF and their combination (magneto-cell) therapies on hyperalgesia and allodynia were investigated by using thermal plantar test and a dynamic plantar aesthesiometer, respectively. In addition, various cytokine levels (IL-1ß, IL-6, and IL-10) of rat sciatic nerve after CCI were analyzed. Following the CCI, both latency and threshold significantly decreased. ADMSC or PMF significantly increased latencies and thresholds. The combination of ADMSC with PMF even more significantly increased latency and threshold when compared with ADMSC alone. However, ADMSC-induced decrease in pro-inflammatory or increase in anti-inflammatory cytokines levels were partially prevented by PMF treatments. Present findings may suggest that both cell-based and magnetic therapies can effectively attenuate chronic neuropathic pain symptoms. Combined magneto-cell therapy may also efficiently reverse neuropathic signs. Bioelectromagnetics. 38:255-264, 2017. © 2017 Wiley Periodicals, Inc.

Frequency-dependent effects of sequenced pulsed magnetic field on experimental diabetic neuropathy.

PURPOSE: Pulsed magnetic field (PMF) as an important non- invasive alternative therapeutic option has been investigated in several pre-clinical and clinical studies. We also hypothesized that sequenced PMF formed with different frequencies can modulate the diabetes-induced neuropathic signs differently. MATERIALS AND METHODS: Therapeutic actions of sequenced PMF including 1, 5, 1, 5 Hz (low (L)-PMF) or 30, 40, 30, 40 Hz (high (H)-PMF) were examined on improving signs and symptoms of diabetic neuropathic pain in the streptozotocin-induced diabetic rat models by measuring nociceptive parameters such as hyperalgesia and allodynia, and various cytokine levels (tumor necrosis factor [TNF]-alpha, interleukin [IL]-1 beta, IL-6 and IL-10) of spinal cord and sciatic nerve tissues. RESULTS: Ameliorating potential of L-PMF application on signs of diabetes is significantly higher than those of H-PMF. L-PMF partially attenuated the diabetes-induced increase in the blood glucose level, enhanced the decreased thresholds and latency during the experiments. Diabetes enhanced the pro-inflammatory cytokine, TNF-alpha, IL-1 beta and IL-6, levels in spinal cord and sciatic nerve of rats. L-PMF treatments to diabetic rats decreased these, but enhanced the production of anti-inflammatory cytokine, IL-10. CONCLUSIONS: The present results demonstrated that sequenced L-PMF treatment can relieve neuropathic signs of diabetes in rats. Anti-hyperglycemic, anti-allodynic and anti-hyperalgesic effects of L-PMF treatment can be closely correlated with each other. Furthermore, decreasing actions of L-PMF on pro-inflammatory/anti-inflammatory cytokine ratio can suggest that the therapeutic potential of L-PMF in diabetes induced neuropathy may involve the regulation of the neuroinflammatory/neuroimmune processes.

Modulation of cytokine levels in ameliorative effects of pulsed magnetic field on an experimental model of Chronic Constriction Injury.

PURPOSE: Clinical chronic neuropathic pain is often resistant to currently used pharmacotherapeutic applications. A number studies have shown that pulsed magnetic field (PMF) application may ameliorate the pain associated with damages, surgeries or diseases. However, possible potential mechanisms of PMF treatments have not been well documented. This study aimed to assess the therapeutic effects of PMF treatment on a Chronic Constriction Injury model (CCI) which mimics clinical chronic neuropathic pain symptoms. MATERIALS AND METHODS: Effects of PMF treatments or sham PMF (SPMF) were investigated by measuring the latencies, thresholds and cytokine levels (interleukin [IL]-1 beta, IL-6 and IL-10) of sciatic nerve in CCI or sham surgery rats. PMF was treated on CCI rats before (a day after surgery, PMF-AD) and after (a week after surgery, PMF-AW) the development of pain signs. RESULTS: Rats exhibited hyperalgesia and allodynia within one week following surgery, and lasted through the experiment. PMF treatments, but not SPMF, significantly enhanced the latency and threshold. Both anti-hyperalgesic and anti-allodynic actions of PMF-AD were greater than those of PMF-AW treatment. Similarly, PMF-AD had more pronounced effects on the level of pro- and anti-inflammatory cytokines than did PMF-AW. CONCLUSIONS: The present findings may suggest that PMF treatment may reverse the CCI-induced changes in neuropathic pain behaviors by decreasing the production of pro-inflammatory cytokines and increasing the anti-inflammatory cytokine production at the site of injury.

Pain-relieving effects of pulsed magnetic fields in a rat model of carrageenan-induced hindpaw inflammation.

PURPOSE: Many strategies have been investigated to exclude the several side-effects of pharmacological or invasive treatments. Non-invasive pulsed magnetic field (PMF) treatment with no toxicity or side-effects can be an alternative to pharmacologic treatments. The purpose of this study was, therefore, to investigate the pain-relieving effects of PMF treatment in the inflammatory pain conditions. MATERIALS AND METHODS: Effects of PMF treatment on the hallmarks of the inflammatory pain indices such as hyperalgesia, allodynia, edema and several biochemical parameters that evaluate oxidative stress were investigated using a well established carrageenan (CAR)-induced hindpaw inflammation model in rats. RESULTS: CAR injection lowered the paw withdrawal thermal latencies (hyperalgesia) and mechanical thresholds (allodynia). CAR also decreased the superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) levels and increased malondialdehyde (MDA) levels compared with healthy rat paw tissues. PMF treatment produced significant increases in the thermal latencies and mechanical thresholds in CAR-injected paws. In the inflamed paw tissues, PMF increased the activities of SOD, CAT and GPx and decreased MDA level. We also demonstrated that PMF decreased paw mass indicating that it has an anti-edematous potential. CONCLUSIONS: The present results reveal that PMF treatment can ameliorate the CAR-induced inflammatory pain indices such as mechanical allodynia, thermal hyperalgesia and edema, and attenuate the oxidative stress. The action mechanisms of PMF in CAR-induced inflammation might be related to the increases in the levels of antioxidant enzymes in inflamed tissues. The findings suggest that PMF treatment might be beneficial in inflammatory pain conditions.

Clodronate changes neurobiological effects of pulsed magnetic field on diabetic rats with peripheral neuropathy.

Several studies have reported that pulsed magnetic fields (PMFs) can be a choice of therapy for diabetic peripheral neuropathy. However, the exact underlying mechanism of PMF is still not known. The purpose of this study was, therefore, to investigate the effects of clodronate encapsulated with liposome, a specific agent depleting macrophage, on PMF-treated streptozotocin-induced type I diabetic rats with peripheral neuropathy. Effects of PMF, liposome-encapsulated clodronate (LEC) or their combined treatments were investigated in diabetic rats by measuring the thermal latencies, mechanical thresholds, whole blood glucose levels, serum insulin level, and body mass. In diabetic rats, PMF exhibited a decrease in the blood glucose levels but did not change the serum insulin level. Both mechanical thresholds and thermal latencies of diabetic rats enhanced throughout the PMF treatment. During the PMF treatment, the administration of LEC suppressed the PMF-induced decrease in blood glucose level, PMF-induced increase in mechanical threshold and thermal latencies in diabetic animals. In addition, PMF reduced the LEC-induced increase in insulin levels of diabetic rats. Findings demonstrated that although effects of both PMF alone and LEC alone on diabetic animals are mostly positive, LEC may remove the therapeutic efficacies of PMF in combined treatment.

Pulsed magnetic fields enhance the rate of recovery of damaged nerve excitability.

Pulsed magnetic fields (PMFs) have well-known beneficial effects on nerve regeneration. However, little research has examined the nerve conduction characteristics of regenerating peripheral nerves under PMF. The main goal of this study was to examine the conduction characteristics of regenerating peripheral nerves under PMFs. The sucrose-gap recording technique was used to examine the conduction properties of injured sciatic nerves of rats exposed to PMF. Following the injury, peripheral nerves were very sensitive to repetitive stimulation. When the stimulation frequency was increased, the amplitude of the compound action potential (CAP) decreased more at 15 days post-crush injury (dpc) than at 38 dpc. PMF treatment for 38 days after injury caused significant differences in the conduction of CAPs. Moreover, application of PMF ameliorated the abnormal electrophysiological activities of nerves such as hyperpolarizing afterpotentials and delayed depolarizations that were revealed by 4-aminopyridine (4-AP). Consequently, characteristic findings in impulse conduction of recovered nerves under PMF indicate that the observed abnormalities in signaling or aberrant ion channel functions following injury may be restored by PMF application.

Neurobiological effects of pulsed magnetic field on diabetes-induced neuropathy.

In the clinic, although several pharmacological agents or surgical procedures are used to treat diabetes and diabetes-induced neuropathic pain, their success has been limited. Therefore, development of different alternatives in treatments is very important. The purpose of this study was to determine the efficacy of pulsed magnetic field (PMF) in improving signs and symptoms of diabetic neuropathy. In this study, the effects of PMF treatment were investigated in Streptozotocin (STZ)-induced acute and chronic diabetic rats by measuring the thermal latencies, mechanical thresholds, whole blood glucose levels and body weights. After STZ administration to rats, blood glucose level elevated and body weight decreased. Although PMF treatment did not affect changes in body weight, the blood glucose levels of PMF-treated diabetic rats exhibited a decrease during the treatments. Diabetic animals displayed marked decrease in mechanical thresholds and thermal latencies. While treatment of PMF partially restored the mechanical thresholds and thermal latency in acute diabetic rats, PMF caused a corrective effect on only mechanical threshold of chronic diabetic rats. These results suggested that treatment of PMF can potentially ameliorate the painful symptoms of diabetes, such as hyperalgesia and allodynia, by partially preventing the hyperglycemia.

Regenerative effects of pulsed magnetic field on injured peripheral nerves.

Previous studies confirm that pulsed magnetic field (PMF) accelerates functional recovery after a nerve crush lesion. The contention that PMF enhances the regeneration is still controversial, however. The influence of a new PMF application protocol (trained PMF) on nerve regeneration was studied in a model of crush injury of the sciatic nerve of rats. To determine if exposure to PMF influences regeneration, we used electrophysiological recordings and ultrastructural examinations. After the measurements of conduction velocity, the sucrose-gap method was used to record compound action potentials (CAPs) from sciatic nerves. PMF treatment during the 38 days following the crush injury enhanced the regeneration. Although the axonal ultrastructures were generally normal, slight to moderate myelin sheath degeneration was noted at the lesion site. PMF application for 38 days accelerated nerve conduction velocity, increased CAP amplitude and decreased the time to peak of the CAP. Furthermore, corrective effects of PMF on. the abnormal characteristics of sensory nerve fibers were determined. Consequently, long-periodic trained-PMF may promote both morphological and electrophysiological properties of the injured nerves. In addition, corrective effects of PMF on sensory fibers may be considered an important finding for neuropathic pain therapy.