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.

BK channel openers NS1619 and NS11021 reverse hydrogen peroxide-induced membrane potential changes in skeletal muscle.

Large conductance calcium-activated potassium (BK) channels play a crucial role in the repolarization and after-hyperpolarization phases of the cell membrane. The channel openers are also used in treatment of some diseases, including hypo/hyperkalemic periodic paralysis. However, little is known about the effects of BK channels and the channel activators on membrane potentials in skeletal muscle. In addition, the effects of reactive oxygen species (ROS) on BK channels in skeletal muscle are also unknown. Therefore, the aim of this study was to determine the effects of BK channel openers and ROS on membrane potentials in skeletal muscle fibers. For this purpose, resting membrane potentials and action potentials (AP) of frog gastrocnemius muscles were recorded in the presence of commonly used BK channel openers NS1619 and NS11021, H2O2 (a type of ROS), and both using intracellular microelectrode technique. The channel activators significantly and dose-dependently decreased amplitude and increased rise time of AP but did not impact repolarization. The presence of H2O2 plus NS1619 or NS11021 resulted in significant change because the channel openers completely reversed the deleterious effects of hydrogen peroxide on the repolarization phase of AP in skeletal muscle fibers. In the present study, the contributions of BK channel activation and the modulatory role of H2O2 on membrane potentials was demonstrated in skeletal muscle fibers, for the first time. Moreover, it should be noted that BK channel openers should be used in the treatment of reactive oxygen species-induced skeletal muscle diseases.

Pulsed magnetic field maintains vascular homeostasis against H2O2-induced oxidative stress.

Pulsed magnetic fields (PMFs) have significant therapeutic effects on many disorders. However, the effects of PMF on vascular homeostasis remain unclear. Therefore, in the present study, we investigated the role of in vivo PMF in maintaining vascular homeostasis during H2O2-induced oxidative stress. For this purpose, rats were exposed to PMF (40 Hz, 1.5 mT) for 1 h for a period of 30 days, following which their thoracic aortas were excised. H2O2 was exogenously applied to the aortic rings. Constrictions were measured in a tissue bath using an electrophysiological technique. Bcl-2 and endothelial nitric oxide synthase (eNOS) protein levels were determined by Western blotting. We found lesser H2O2-induced vasoconstriction in the PMF group than in the control group in endothelium-intact (E+) rings. As H2O2 also induces apoptosis, after incubation with H2O2 (40 min) to induce early apoptosis, we added KCl and measured KCl-induced contractions. All the groups, endothelium intact or denuded (E-) showed decreased responses; however, we still observed the effect of PMF in the E+ group due to increased endothelial activity. In addition, PMF increased the expression of the eNOS protein, which might be a key target of PMF. Our results suggest that in vivo application of PMF protects vascular responses through endothelium-mediated mechanisms during oxidative stress. Therefore, PMF might play a protective role against vascular diseases.

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.

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.

Cysteine challenge test as a novel diagnostic tool to distinguish oral halitosis.

BACKGROUND: The cysteine challenge test is often used to check the H2 S production capacity of the mouth. Patients with oral halitosis group (n = 305) or non-oral halitosis group (n = 191) and healthy individuals (control group, n = 102) were compared with each other to identify any possible relationship between initial and cysteine-induced oral H2 S concentrations. SUBJECTS AND METHOD: The medical records of 598 participants were reviewed retrospectively. Oral H2 S concentrations before (pre-CR) and after cysteine rinse (post-CR) with 5 mL of 20 mmol L-cysteine solution for 30 s were compared. RESULTS: Pre-CR H2 S concentrations were >0.8 ppm in 75.1% of oral group patients but less than <0.8 ppm in 87.3% of the non-oral group and 86.9% of controls. After cysteine rinse, oral H2 S concentrations exceeded 12 ppm in 72% of the oral halitosis patients but were lower in 88% of non-oral group and 99% of controls. Whilst post-CR/pre-CR ratio was >12 in 74.5% of the oral group, it was <12 in 81.7% of the non-oral group and 83.4% of controls. CONCLUSION: Cysteine challenge test can be used as a diagnostic tool to identify an individual's tendency to produce oral malodor, not only to quantify momentary halitosis level.

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.

The effect of very low dose pulsed magnetic waves on cochlea.

INTRODUCTION: In daily life biological systems are usually exposed to magnetic field forces at different intensities and frequencies, either directly or indirectly. Despite negative results, the therapeutic use of the low dose magnetic field has been found in recent studies. The effect of magnetic field forces on cochlear cells is not clear in the literature. OBJECTIVE: In our study, we first applied in vivo pulsed magnetic fields to laboratory rats to investigate the effects on cochlea with distortion product otoacoustic emission test followed by histopathological examinations. METHODS: Twelve rats were included in this study, separated into two groups as study group and control group. The rats in the study group were exposed to 40Hz pulsed magnetic field for 1h/day for 30 days; the hearing of the rats was controlled by otoacoustic emission test. Also, their cochleas were removed and histochemical examination was performed by Caspase-3, Caspase-9, and TUNEL methods. RESULTS: A statistically significant difference was determined (p<0.05) when the hearing thresholds of the groups obtained by using 5714Hz and 8000Hz stimuli were compared by Kruskal-Wallis test. A significant reaction was observed in the study group, especially in the outer ciliated cells during immunohistochemical examinations by using Caspase-3 and Caspase-9 methods. A significantly positive difference was determined in the study group, especially at the outer ciliated cells and the support cells of the corti organ, when compared to the control group (p<0.05) by the TUNEL method. CONCLUSION: According to the results of our study, the very low dose magnetic field, which is considered to be used for therapeutic purposes recently, can cause both auditory function defects and histopathologic damage in cochlear cells.

Effects of rosiglitazone on altered electrical left ventricular papillary muscle activities of diabetic rat.

The action potential configuration of the left ventricular papillary muscle as well as the rosiglitazone-dependent changes in ventricular papillary muscle action potential amplitude were studied, and the duration was studied and compared in both healthy and diabetic rats. In this study, we used four groups: (1) nondiabetic control animals (C), (2) rosiglitazone-treated nondiabetic control animals (C+RSG), (3) diabetic animals (D), and (4) rosiglitazone-treated diabetic animals (D+RSG). Diabetes was induced by a single intravenous (i.v.) injection of streptozotocin (STZ). Conventional microelectrode techniques were applied to record action potentials after the establishment of diabetes (8 weeks after STZ treatment). Resting membrane potential (RMP) was decreased significantly in both RSG-treated C and D rats (from -70.2 +/- 0.7 to -63.2 +/- 0.7 and from -69.2 +/- 0.4 to -61.2 +/- 0.4). C+RSG and D+RSG groups showed increase in action potential amplitude compared with C and D groups (from 67.1 +/- 0.8 to 68.2 +/- 0.5 and from 67.1 +/- 0.8 to 80.1 +/- 0.8 and from 68.2 +/- 0.5 to 79.3 +/- 0.3) Depolarization time was significantly prolonged in diabetic rats (12.1 +/- 0.4 to 27.5 +/- 0.9). However, this prolongation in D+RSG group was significantly lower according to D group (from 27.5 +/- 0.9 to 19.2 +/- 0.7). There was no difference between C and C+RSG rats (12.1 +/- 0.4 to 11.6 +/- 0.2). Half repolarization time was also prolonged in diabetic rats (17.5 +/- 0.6 to 59.9 +/- 1.0). Moreover, D+RSG rats showed a slight and statistically insignificant difference according D rats (59.9 +/- 1.0 to 55.9 +/- 1.7). C+RSG rats showed a slight significant increase in half repolarization time compared with C group (17.5 +/- 0.6 to 29.4 +/- 0.7). Treatment of rats with RSG markedly decreased insulin resistance and also increased insulin sensitivity of the heart. Our data suggest that the beneficial effects of RSG treatment on the electrical activities of the diabetic rat papillary appear to be due to the diminished K+ currents, partially related to the decrease of hyperglycemia.

The effects of rosiglitazone on oxidative stress and lipid profile in left ventricular muscles of diabetic rats.

We investigated the effect of rosiglitazone (RSG), a high-affinity ligand for the peroxisome proliferator-activated receptor gamma which mediates insulin-sensitizing actions, on the lipid profile and oxidative status in streptozotocin (STZ)-induced Type 2 diabetes mellitus (DM) rats. Wistar albino male rats were randomly divided into an untreated control group (C), a C + RSG group which was treated with RSG (4 mg kg(-1)) two times a day by gavage, a diabetic group (D) that was treated with a single intraperitoneal injection of STZ (45 mgkg(-1)), D + RSG group which were treated with RSG two times a day by gavage, respectively. Lipid profiles, HbA(1c) and blood glucose levels in the circulation and malondialdehyde (MDA) and 3-nitrotyrosine (3-NT) levels in left ventricular muscle were measured. Treatment of D rats with RSG resulted in a time-dependent decrease in blood glucose. We found that the lipid profile and HbA(1c) levels in D + RSG group reached the C rat values at the end of the treatment period. There was a statistically significant difference between the C + RSG and C groups in 3-NT levels. In group D, 3-NT and MDA levels were found to be increased when compared with C, C + RSG and D + RSG groups. In the D + RSG group, MDA levels were found to be decreased when compared with C and C + RSG. Our study suggests that the treatment of D rats with RSG for 8 weeks may decrease the oxidative/nitrosative stress in left ventricular tissue of rats. Thus in diabetes-related vascular diseases, RSG treatment may be cardioprotective.

Role of 4-aminopyridine-sensitive potassium channels in peripheral antinociception.

Previous studies has report the modulation of K+ channels play key roles in the induction of peripheral antinociception induced by many types of drugs. However, the possible participation of 4-aminopyridine-sensitive K+ channels to local antinociception induced by tramadol, a mu opioid receptor agonist, and lidocaine, a local anaesthetic, has been less studied. In this study, we therefore investigated this by using thermal plantar test. Tramadol or lidocaine administered intraplantarly into the hind paw elicited an antinociceptive effect. 4-aminopyridine caused an increase in the antinociception produced by lidocaine. However, tramadol induced antinociception remained unaffected by intraplantar administration of 4-aminopyridine. These results suggest that 4-aminopyridine-sensitive K+ channels may play an important role in the thermal peripheral antinociception produced by lidocaine, but not tramadol.

Local analgesic efficacy of tramadol following intraplantar injection.

Several studies have suggested that systemic tramadol, an opioid, can represent a valuable treatment in severe pain conditions because of their effects on central pain pathways. However, there are not enough studies supporting that tramadol is efficacious when administered locally. Therefore, we studied the potential local analgesic effects of tramadol in peripheral nociception. In addition, we tested the antinociceptive effects of tramadol-CaCl(2) or naloxone combinations after subcutaneous intraplantar injection in a validated rat model of acute thermal nociception. Local analgesic effects of tramadol were compared with those of lidocaine. The effects of tramadol on thermal paw withdrawal latencies were monitored using the plantar test. The antinociceptive potency of tramadol is higher and long-lasting than that of lidocaine. Naloxone was unable to inhibit the increased antinociceptive response produced by tramadol. Ca(2+) modified the effect of tramadol. When Ca(2+) dose was increased in the solution, thermal antinociceptive potency of tramadol, but not lidocaine was prolonged. Thermal nociceptive responses were not affected in the non-injected paws, indicating a lack of systemic effects with doses of tramadol and lidocaine that elicited local analgesia. These results suggest that intraplantar tramadol administration can produce local analgesic effect with a different action mechanism than that of lidocaine. In addition, extracellular Ca(2+) may play an important role in the local analgesic action of tramadol.

The actions of lamotrigine and levetiracetam on the conduction properties of isolated rat sciatic nerve.

The purpose of this study was to investigate the actions of lamotrigine and levetiracetam on the conduction properties of isolated rat sciatic nerves in-vitro. Compound action potentials from rat sciatic nerves were recorded using a sucrose-gap technique with single and repetitive stimulation. Lamotrigine, at 0.01 to 1 mM, reduced the amplitude of compound action potentials (3.9+/-0.6% to 47.9+/-2.4%) and produced at high frequency dependent (phasic) and independent (tonic) conduction block. Lamotrigine extended the peak time of the compound action potentials significantly without changing the half falling-time (P<0.05). Lamotrigine reduced the amplitude of the delayed depolarization, which was more pronounced than that of the amplitude of the compound action potentials in the presence of 4-aminopyridine. With tonic and phasic stimulation, 0.1 to 10 mM of levetiracetam did not alter the amplitude, peak time and half falling time of the compound action potentials. In addition, levetiracetam did not change the amplitude of the delayed depolarization and the area of the compound action potentials following application of 4-aminopyridine. These results indicate that lamotrigine produces a powerful tonic block with delayed depolarization, whereas it produces a weaker phasic block in rat sciatic nerve. Levetiracetam has no effect on peripheral nerve conduction even at high concentrations. These results may have the relevance to our understanding of the peripheral effects of lamotrigine and levetiracetam.

Comparative effects of lidocaine and tramadol on injured peripheral nerves.

The aim of the present study was to investigate the action of lidocaine and tramadol on the abnormal impulse characteristics of injured peripheral nerves. The ultrastructure of nerves was studied with electron microscopy and the action of lidocaine and tramadol on intact and injured rat sciatic nerves was examined by using the sucrose gap recording technique. Tramadol and lidocaine caused concentration- and frequency-dependent decreases in the amplitude of the compound action potential. Injured nerves were more sensitive to lidocaine than to tramadol. Lidocaine suppressed the delayed depolarization and decreased the hyperpolarizing afterpotentials to a greater extent than did tramadol. A low concentration of lidocaine may restore the abnormal impulse characteristics of injured nerves without changing the normal impulse pattern. The efficacy of lidocaine and inefficacy of tramadol on abnormal impulse characteristics may contribute, at least in part, to our understanding of the mechanisms of action of these drugs in neuropathic pain therapy.

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.

Alterations in conduction characteristics of crushed peripheral nerves.

PURPOSE: Nerve crush injury results in the incapability to maintain conduction of an impulse. Disruption in the myelin sheath causes very important changes in the activities of ion channels. Therefore, crushed and intact sciatic nerves were researched with both histological and electrophysiological methods in this study. METHODS: Electron and light microscopy for histological examinations, a sucrose-gap recording techniques for electrophysiological examinations were used. 4-aminopyridine (4-AP) and Tetraethylammonium (TEA) were used to functional separation of the fast and slow K;+ channels. RESULTS: The number of damaged myelinated nerve fiber was counted as 750 +/- 3.5. Lamellar separation and disruption in myelin sheath was frequently observed in these fibers. Conduction velocity of crushed nerves (19 +/- 2 m/s) was half of the intact nerves. The relationship between equally spaced interstimulus interval and their responses demonstrated that 4-AP and 4-AP plus TEA have more pronounced effects on crushed nerves than on intact nerves. After 4-AP, TEA application caused an efficiently depolarization in the membrane potential. CONCLUSIONS: The effects of 4-AP and 4-AP plus TEA suggest the involvement of slow and fast K;+ channels and slow Na;+ currents in membrane potential and action potential repolarization. Minimal myelin damage may significantly influence the subsequent impulse generation and the patterning of action potential activity.

[Effect of tramadol on regeneration after experimental sciatic nerve injury]. / Deneysel siyatik sinir hasarinin rejenerasyonunda tramadolün etkisi.

Abnormal impulses in peripheral nerves play a critical role in neuropathic pain syndromes. The voltage-gated Na+ channels that underlie the action potential are main targets for clinically useful drugs in the pain therapy. Systemic tramadol has been shown to have clinical efficacy against some forms of neuropathic pain. Therefore, we investigated the mechanisms of action of tramadol by an in vitro model by sucrose-gap technique. Tramadol produced concentration-dependent and frequency-dependent decrements in CAP amplitude. Also, injured nerves were more sensitive to tramadol. Tramadol decreased the amplitude of the delayed depolarization and the hyperpolarizing afterpotentials. In conclusion, blocking potencies of small concentration tramadol on the delayed depolarization and hyperpolarizing afterpotential in regeneration period may be contributed for understanding of the action mechanisms of tramadol on neuropathic pain therapy.

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.