Neuropathy – Neuropathic Pain

Neurosci Behav Physiol. 2010 Mar;40(3):347-50.

Non-pharmacological correction of impaired microcirculation in children with diabetic polyneuropathy.

Nikolaeva NV, Bolotova NV, Luk’yanov VF, Raigorodskii YM, Tkacheva EN.

Saratov State Medical University, Saratov, Russia.

Abstract

A total of 25 boys and 20 girls aged 5-17 years with type I diabetes mellitus and disease durations of 2-10 years were studied. All had diabetic polyneuropathy. The microcirculation was studied by laser Doppler flowmetry. Treatment consisted of using a running impulse magnetic field. This method was found to be effective in diabetic polyneuropathy with the running field along the limb towards the periphery at a run velocity (field modulation frequency) being a multiple of the nerve fiber spike conduction velocity.

Bioelectromagnetics. 2010 Jan;31(1):39-47.

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

Mert T, Gunay I, Ocal I.

Faculty of Medicine, Department of Biophysics, Cukurova University, Balcali, Adana, Turkey.tufanmert@yahoo.com

Abstract

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. (c) 2009 Wiley-Liss, Inc.

Bioelectromagnetics. 2009 Sep;30(6):438-45.

Exposure of inhomogenous static magnetic field ceases mechanical allodynia in neuropathic pain in mice.

Antal M, László J.

Department of Anatomy, Histology, and Embriology, University of Debrecen, Debrecen, Hungary.

Abstract

Magnetic therapy as a self-care intervention has led to the conduct of numerous human trials and animal experiments. Results concerning the analgesic efficacy of magnetic exposure, however, are inconsistent. By using a magnetic device generating an inhomogeneous static magnetic field (iSMF), here we studied how the whole-body exposure to iSMF may influence the mechanical withdrawal threshold (MWT) of the hind paw in different stages of neuropathic pain evoked by partial ligation of the sciatic nerve in mice. It was found that iSMF exposure did not prevent the decrease of MWT in the first postoperative week. A 2-week long iSMF treatment that was started just after the nerve ligation elevated MWT values to a modest extent. However, the effectiveness of a daily exposure to iSMF was much more prominent when it was applied between postoperative days 15 and 28. In this case, MWT was already noticeably increased after the first treatment and it practically reached the control values by the end of the 2-week long exposure period. The results suggest that exposure to iSMF cannot prevent the development of mechanical allodynia, but can inhibit processes that maintain the increased sensitivity to mechanical stimuli in neuropathic pain.

Arch Phys Med Rehabil. 2009 Jul;90(7):1102-9.

Pulsed electromagnetic fields to reduce diabetic neuropathic pain and stimulate neuronal repair: a randomized controlled trial.

Weintraub MI, Herrmann DN, Smith AG, Backonja MM, Cole SP.

Department of Neurology, New York Medical College, Valhalla, NY, USA. miwneuro@pol.net

Abstract

OBJECTIVE: To determine whether repetitive and cumulative exposure to low-frequency pulsed electromagnetic fields (PEMF) targeting painful feet can reduce neuropathic pain (NP), influence sleep in symptomatic diabetic peripheral neuropathy (DPN), and influence nerve regeneration.

DESIGN: Randomized, double-blind, placebo-controlled parallel study.

SETTING: Sixteen academic and clinical sites in 13 states.

PARTICIPANTS: Subjects (N=225) with DPN stage II or III were randomly assigned to use identical devices generating PEMF or sham (placebo) 2 h/d to feet for 3 months.

INTERVENTIONS: Nerve conduction testing was performed serially.

MAIN OUTCOME MEASURES: Pain reduction scores using a visual analog scale (VAS), the Neuropathy Pain Scale (NPS), and the Patient’s Global Impression of Change (PGIC). A subset of subjects underwent serial 3-mm punch skin biopsies from 3 standard lower limb sites for epidermal nerve fiber density (ENFD) quantification.

RESULTS: Subjects (N=225) were randomized with a dropout rate of 13.8%. There was a trend toward reductions in DPN symptoms on the PGIC, favoring the PEMF group (44% vs 31%; P=.04). There were no significant differences between PEMF and sham groups in the NP intensity on NPS or VAS. Twenty-seven subjects completed serial biopsies. Twenty-nine percent of PEMF subjects had an increase in distal leg ENFD of at least 0.5 SDs, while none did in the sham group (P=.04). Increases in distal thigh ENFD were significantly correlated with decreases in pain scores.

CONCLUSIONS: PEMF at this dosimetry was noneffective in reducing NP. However neurobiological effects on ENFD, PGIC and reduced itching scores suggest future studies are indicated with higher dosimetry (3000-5000 G), longer duration of exposure, and larger biopsy cohort.

Zh Nevrol Psikhiatr Im S S Korsakova. 2008;108(11):43-6.

Non-pharmacological treatment of microcirculation disturbance in children with diabetic polyneuropathy.

[Article in Russian]

Nikolaeva NV, Bolotova V, Luk’ianov VF, Ra?gorodski? IuM, Tkacheva EN.

Abstract

Twenty-five boys and 20 girls, aged 5-17 years, with diabetes mellitus type I and illness duration from 2 to 10 years have been studied. All of them suffered from diabetic neuropathy. Laser-Doppler flowmetry has been used. The treatment has been conducted using running impulse magnetic field. The efficacy of the influence of running field along the extremity with the velocity of run (frequency of field modulation) divisible by the impulse conduction velocity along the nerve fiber in diabetic polyneuropathy has been shown.

Altern Ther Health Med. 2006 Sep-Oct;12(5):42-9

Regenerative effects of pulsed magnetic field on injured peripheral nerves.

Mert T, Gunay I, Gocmen C, Kaya M, Polat S.

Department of Biophysics, University of Cukurova School of Medicine, Adana, Turkey.

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.

Diabetologia. 2005 May;48(5):817-23. Epub 2005 Apr 15.

Effectiveness of frequency-modulated electromagnetic neural stimulation in the treatment of painful diabetic neuropathy.

Bosi E, Conti M, Vermigli C, Cazzetta G, Peretti E, Cordoni MC, Galimberti G, Scionti L.

Diabetes and Endocrinology Unit, Department of General Medicine, Vita-Salute San Raff aele University Hospital, Via Olgettina 60, 20132 Milan, Italy. bosi.emanuele@hsr.it

Abstract

AIMS/HYPOTHESIS: The largely unsatisfactory results reported for the pharmacological treatment of diabetic neuropathy has spurred the search for alternative therapies. The aim of this study was to evaluate the efficacy of frequency-modulated electromagnetic neural stimulation (FREMS) as a novel treatment for painful diabetic neuropathy.

METHODS: Patients (n=31) with painful neuropathy associated with decreased nerve conduction velocity (<40 m/s) and increased vibration perception threshold (>25 V) were enrolled in a randomised, double-blind, crossover study designed to compare the effects of FREMS with those of placebo. Each patient received two series of ten treatments of either FREMS or placebo in random sequence, with each series lasting no more than 3 weeks. The primary efficacy end point was the change in pain measured by a visual analogue scale (VAS).

RESULTS: FREMS induced a significant reduction in daytime and night-time VAS pain score (all p<0.02). Furthermore, FREMS induced a significant increase in sensory tactile perception, as assessed by monofilament; a decrease in foot vibration perception threshold, as measured by a biothesiometer; and an increase in motor nerve conduction velocity (all p<0.01). No significant changes were observed after placebo. Comparison of measurements at the 4-month follow-up with those at baseline revealed that a significant benefit persisted for all measures that showed an improvement at the end of treatment, with an additional improvement in quality of life evaluated by the Short Form-36 questionnaire (all p<0.05). No significant side effects were recorded during the study.

CONCLUSIONS/INTERPRETATION: FREMS is a safe and effective therapy for neuropathic pain in patients with diabetes and is able to modify some parameters of peripheral nerve function.

Neurorehabil Neural Repair. 2004 Mar;18(1):42-6.

Pulsed magnetic field therapy in refractory neuropathic pain secondary to peripheral neuropathy: electrodiagnostic parameters–pilot study.

Weintraub MI, Cole SP.

New York Medical College, Briarcliff Manor, New York 10510, USA.

CONTEXT: Neuropathic pain (NP) from peripheral neuropathy (PN) arises from ectopic firing of unmyelinated C-fibers with accumulation of sodium and calcium channels. Because pulsed electromagnetic fields (PEMF) safely induce extremely low frequency (ELF) quasirectangular currents that can depolarize, repolarize, and hyperpolarize neurons, it was hypothesized that directing this energy into the sole of one foot could potentially modulate neuropathic pain.

OBJECTIVE: To determine if 9 consecutive 1-h treatments in physician’s office (excluding weekends) of a pulsed signal therapy can reduce NP scores in refractory feet with PN.

DESIGN/SETTING/PATIENTS: 24 consecutive patients with refractory and symptomatic PN from diabetes, chronic inflammatory demyelinating polyneuropathy (CIDP), pernicious anemia, mercury poisoning, paraneoplastic syndrome, tarsal tunnel, and idiopathic sensory neuropathy were enrolled in this nonplacebo pilot study. The most symptomatic foot received therapy. Primary endpoints were comparison of VAS scores at the end of 9 days and the end of 30 days follow-up compared to baseline pain scores. Additionally, Patients’ Global Impression of Change (PGIC) questionnaire was tabulated describing response to treatment. Subgroup analysis of nerve conduction scores, quantified sensory testing (QST), and serial examination changes were also tabulated. Subgroup classification of pain (Serlin) was utilized to determine if there were disproportionate responses.

INTERVENTION: Noninvasive pulsed signal therapy generates a unidirectional quasirectangular waveform with strength about 20 gauss and a frequency about 30 Hz into the soles of the feet for 9 consecutive 1-h treatments (excluding weekends). The most symptomatic foot of each patient was treated.

RESULTS: All 24 feet completed 9 days of treatment. 15/24 completed follow-up (62%) with mean pain scores decreasing 21% from baseline to end of treatment (P=0.19) but with 49% reduction of pain scores from baseline to end of follow-up (P<0.01). Of this group, self-reported PGIC was improved 67% (n=10) and no change was 33% (n=5). An intent-to-treat analysis based on all 24 feet demonstrated a 19% reduction in pain scores from baseline to end of treatment (P=0.10) and a 37% decrease from baseline to end of follow-up (P<0.01). Subgroup analysis revealed 5 patients with mild pain with nonsignificant reduction at end of follow-up. Of the 19 feet with moderate to severe pain, there was a 28% reduction from baseline to end of treatment (P<0.05) and a 39% decrease from baseline to end of follow-up (P<0.01). Benefit was better in those patients with axonal changes and advanced CPT baseline scores. The clinical examination did not change. There were no adverse events or safety issues.

CONCLUSIONS: These pilot data demonstrate that directing PEMF to refractory feet can provide unexpected short term analgesic effects in more than 50% of individuals. The role of placebo is not known and was not tested. The precise mechanism is unclear yet suggests that severe and advanced cases are more magnetically sensitive. Future studies are needed with randomized placebo-controlled design and longer treatment periods.

Arch Phys Med Rehabil. 2003 May;84(5):736-46.

Static magnetic field therapy for symptomatic diabetic neuropathy: a randomized, double-blind, placebo-controlled trial.

Weintraub MI, Wolfe GI, Barohn RA, Cole SP, Parry GJ, Hayat G, Cohen JA, Page JC, Bromberg MB, Schwartz SL

Magnetic Research Group. Department of Neurology, New York Medical College, Valhalla, NY, USA. miwneuro@pol.net

OBJECTIVE: To determine if constant wearing of multipolar, static magnetic (450G) shoe insoles can reduce neuropathic pain and quality of life (QOL) scores in symptomatic diabetic peripheral neuropathy (DPN). DESIGN: Randomized, placebo-control, parallel study.

SETTING: Forty-eight centers in 27 states.

PARTICIPANTS: Three hundred seventy-five subjects with DPN stage II or III were randomly assigned to wear constantly magnetized insoles for 4 months; the placebo group wore similar, unmagnetized device.

INTERVENTION: Nerve conduction and/or quantified sensory testing were performed serially.

MAIN OUTCOME MEASURES: Daily visual analog scale scores for numbness or tingling and burning and QOL issues were tabulated over 4 months. Secondary measures included nerve conduction changes, role of placebo, and safety issues. Analysis of variance (ANOVA), analysis of covariance (ANCOVA), and chi-square analysis were performed.

RESULTS: There were statistically significant reductions during the third and fourth months in burning (mean change for magnet treatment, -12%; for sham, -3%; P<.05, ANCOVA), numbness and tingling (magnet, -10%; sham, +1%; P<.05, ANCOVA), and exercise-induced foot pain (magnet, -12%; sham, -4%; P<.05, ANCOVA). For a subset of patients with baseline severe pain, statistically significant reductions occurred from baseline through the fourth month in numbness and tingling (magnet, -32%; sham, -14%; P<.01, ANOVA) and foot pain (magnet, -41%; sham, -21%; P<.01, ANOVA).

CONCLUSIONS: Static magnetic fields can penetrate up to 20mm and appear to target the ectopic firing nociceptors in the epidermis and dermis. Analgesic benefits were achieved over time.

Fiziol Zh. 2003;49(2):85-90.

Use of low-power electromagnetic therapy in diabetic polyneuropathy.

[Article in Ukrainian]

Chebotar’ova LL, Chebotar’ov HIe.

Abstract

The clinical-electroneuromyography investigations were performed for objective evaluation of low-power electromagnetic therapy effectiveness in 12 patients with diabetic polyneuropaties. It is established that combination of low-power electromagnetic therapy using “ANET-UHF”, “ANET-SHF” apparatus (Ukraine) and low-power variable magnetic field using AMT apparatus (Ukraine) give the stable positive effects. The positive changes were confirmed by following: the decrease of neurological deficit and required insulin daily dose, nerve conduction velocity increase, increase of the muscle compound action potentials (muscle power) and peripheral outflow in some patients.

Neurosci Behav Physiol. 2003 Oct;33(8):745-52.

The use of pulsed electromagnetic fields with complex modulation in the treatment of patients with diabetic polyneuropathy.

Musaev AV, Guseinova SG, Imamverdieva SS.

Science Research Institute of Medical Rehabilitation, Baku, Azerbaidzhan.

Clinical and electroneuromyographic studies were performed in 121 patients with diabetic polyneuropathy (DPN) before and after courses of treatment with pulsed electromagnetic fields with complex modulation (PEMF-CM) at different frequencies (100 and 10 Hz). Testing of patients using the TSS and NIS LL scales demonstrated a correlation between the severity and frequency of the main subjective and objective effects of disease and the stage of DPN. The severity of changes in the segmental-peripheral neuromotor apparatus–decreases in muscle bioelectrical activity, the impulse conduction rate along efferent fibers of peripheral nerves, and the amplitude of the maximum M response–depended on the stage of DPN and the duration of diabetes mellitus. The earliest and most significant electroneuromyographic signs of DPN were found to be decreases in the amplitude of the H reflex and the Hmax/Mmax ratio in the muscles of the lower leg. Application of PEMF-CM facilitated regression of the main clinical symptoms of DPN, improved the conductive function of peripheral nerves, improved the state of la afferents, and improved the reflex excitability of functionally diverse motoneurons in the spinal cord. PEMF-CM at 10 Hz was found to have therapeutic efficacy, especially in the initial stages of DPN and in patients with diabetes mellitus for up to 10 years.

Vopr Kurortol Fizioter Lech Fiz Kult. 1993 Sep-Oct;(5):38-41.

The use of combined methods of magnetoelectrotherapy in treating polyneuropathies.

[Article in Russian]

Shiman AG, Lobzin VS, Maksimov AV, Zabolokov IG.

A comparative evaluation by such parameters as alleviation of pain syndrome, improvement of peripheral resistance and vegetotrophic processes, a decline in pareses and sensory disorders has been performed in 3 groups of patients: group 1 underwent benzohexonium electrophoresis, group 2 benzohexonium electrophoresis in the magnetic field produced by the unit “Polyus-I” followed by low-frequency electrotherapy with bipolar impulse current, group 3 benzohexonium electrophoresis in the magnetic field from the unit “ADMT-Magnipuls” followed by low-frequency electrotherapy with bipolar impulse current. The best clinical and physiological results were reported in group 3 patients.

Wiad Lek. 2003;56(9-10):434-41.

Application of variable magnetic fields in medicine–15 years experience.

[Article in Polish]

Sieron A, Cieslar G.

Katedra i Klinika Chorob Wewnetrznych, Angiologii i Medycyny Fizykalnej SAM, ul. Batorego 15, 41-902 Bytom. sieron@mediclub.pl

The results of 15-year own experimental and clinical research on application of variable magnetic fields in medicine were presented. In experimental studies analgesic effect (related to endogenous opioid system and nitrogen oxide activity) and regenerative effect of variable magnetic fields with therapeutical parameters was observed. The influence of this fields on enzymatic and hormonal activity, free oxygen radicals, carbohydrates, protein and lipid metabolism, dielectric and rheological properties of blood as well as behavioural reactions and activity of central dopamine receptor in experimental animals was proved. In clinical studies high therapeutic efficacy of magnetotherapy and magnetostimulation in the treatment of osteoarthrosis, abnormal ossification, osteoporosis, nasosinusitis, multiple sclerosis, Parkinson’s disease, spastic paresis, diabetic polyneuropathy and retinopathy, vegetative neurosis, peptic ulcers, colon irritable and trophic ulcers was confirmed.

Lik Sprava. 1996 Oct-Dec;(10-12):155-8.

The medical effect of magnetic-laser therapy in patients with diabetic angiopathies of the lower extremities.

[Article in Ukrainian]

Shved MI, Dudnik AP.

Conventional antidiabetic therapy with insulin and sugar-lowering agents helps in achieving compensation of diabetes mellitus but fails to exert high effect on subjective and objective manifestations of diabetic microangiopathies of the lower extremities. A course of magnetic-laser therapy results in significant reduction of concentration of the lipid oxidation products as one of the pathogenetic mechanisms of diabetic microangiopathies, normalization of immunologic reactivity as well as attenuation of clinical manifestations of hemocirculatory disorders in the lower extremities and improvement of parameters of thermo- and rheovasography.

Klin Med (Mosk). 1996;74(5):39-41.

Magentotherapy in the comprehensive treatment of vascular complications of diabetes mellitus.

[Article in Russian]

Kirillov IB, Suchkova ZV, Lastushkin AV, Sigaev AA, Nekhaeva TI.

320 diabetes mellitus (DM) patients were exposed to impulsed magnetic field, 100 control DM patients received conservative therapy alone. 270 patients had microangiopathy, macroangiopathy was diagnosed in 50 patients. Good and satisfactory results of magnetotherapy in combination with conservative methods were achieved in 74% of patients versus 28% in control group. Metabolism stabilization resulted in some patients in reduced blood sugar. Use of magnetic field produced faster and longer response than conservative therapy.

Srp Arh Celok Lek. 1993 Aug-Dec;121(8-12):124-6.

Use of pulsating high-frequency electromagnetic fields in patients with diabetic neuropathies and angiopathies.

[Article in Serbian]

Vesovi?-Poti? V, Coni? S.

Belgrade Institute of Rehabilitation.

Abstract

High-frequency pulsating electromagnetic field therapy was carried out in 22 patients with diabetic polyneuropathy and angiopathy manifested on lower extremities (18 men, 4 women, aged 48.2 +/- 6.3 years; 10 insulin-dependent persons, and 12 on oral antidiabetic treatment). The aim of the study was to verify the effect of this therapy on symptoms, neurophysiological findings and peripheral circulation. The diagnose of diabetic polyneuropathy was based on the electromyographic examination of foot and calf muscles, measurement of motor nerve conduction velocity of peroneal and tibial nerve, and sensory nerve conduction velocity of sural nerve. Diagnosis of diabetic polyneuropathy was based on electromyographic examination of the foot and calf muscles, measurement of the motor nerve conduction velocity of peroneal and tibial nerves, and the sensory nerve conduction velocity of the sural nerve. Diagnosis of diabetic angiopathy was established by oscillometric examination, measurement of skin temperature and claudication distance. The same methods were used for the evaluation of the therapeutical effect of electromagnetic field. Significant improvement of symptoms, and of all registered parameters of peripheral circulation was established after the therapy, but there were no significant changes of neurophysiological parameters. Therefore, high-frequency pulsating electromagnetic field is recommended for the treatment of diabetic angiopathy. In patients with neuropathic changes it can be used as an introduction procedure, or as an additional procedure to physical agents which are commonly used in the treatment of peripheral nerve lesion.