Effectiveness of Photobiomodulation Therapy on Neuropathic Pain, Nerve Conduction and Plantar Pressure Distribution in Diabetic Peripheral Neuropathy - A Systematic Review.

BACKGROUND: Diabetic peripheral neuropathy is a severe complication of type 2 diabetes mellitus. The most common symptoms are neuropathic pain and altered sensorium due to damage to small nerve fibers. Altered plantar pressure distribution is also a major risk factor in diabetic peripheral neuropathy, leading to diabetic foot ulcers. OBJECTIVE: The objective of this systematic review was to analyze the various studies involving photobiomodulation therapy on neuropathic pain and plantar pressure distribution in diabetic peripheral neuropathy. METHODS: We conducted a systematic review (PubMed, Web of Science, CINAHL, and Cochrane) to summarise the evidence on photobiomodulation therapy for Diabetic Peripheral Neuropathy with type 2 diabetes mellitus. Randomized and non-randomized studies were included in the review. RESULTS: This systematic review included eight studies in which photobiomodulation therapy showed improvement in neuropathic pain and nerve conduction velocity. It also reduces plantar pressure distribution, which is a high risk for developing foot ulcers. CONCLUSION: We conclude that photobiomodulation therapy is an effective, non-invasive, and costefficient means to improve neuropathic pain and altered plantar pressure distribution in diabetic peripheral neuropathy.

Anti-hyperalgesic effects of photobiomodulation therapy (904 nm) on streptozotocin-induced diabetic neuropathy imply MAPK pathway and calcium dynamics modulation.

Several recent studies have established the efficacy of photobiomodulation therapy (PBMT) in painful clinical conditions. Diabetic neuropathy (DN) can be related to activating mitogen-activated protein kinases (MAPK), such as p38, in the peripheral nerve. MAPK pathway is activated in response to extracellular stimuli, including interleukins TNF-α and IL-1ß. We verified the pain relief potential of PBMT in streptozotocin (STZ)-induced diabetic neuropathic rats and its influence on the MAPK pathway regulation and calcium (Ca2+) dynamics. We then observed that PBMT applied to the L4-L5 dorsal root ganglion (DRG) region reduced the intensity of hyperalgesia, decreased TNF-α and IL-1ß levels, and p38-MAPK mRNA expression in DRG of diabetic neuropathic rats. DN induced the activation of phosphorylated p38 (p-38) MAPK co-localized with TRPV1+ neurons; PBMT partially prevented p-38 activation. DN was related to an increase of p38-MAPK expression due to proinflammatory interleukins, and the PBMT (904 nm) treatment counteracted this condition. Also, the sensitization of DRG neurons by the hyperglycemic condition demonstrated during the Ca2+ dynamics was reduced by PBMT, contributing to its anti-hyperalgesic effects.

Low level light therapy/photobiomodulation for diabetic peripheral neuropathy: protocol of a systematic review and meta-analysis.

INTRODUCTION: Diabetic peripheral neuropathy (DPN) is one of the most common complications of diabetes that strongly impact the patients' quality of life and working ability. Evidence indicated that low level light therapy (LLLT)/photobiomodulation might be effective for neuropathy. However, the effect of LLLT for DPN is not clear. The objective of this systematic review and meta-analysis is to determine the effects and safety of LLLT/photobiomodulation for DPN, in comparison with other methods such as sham light, no treatment, other active treatment and LLLT as an additional treatment compared with another treatment alone. METHODS AND ANALYSIS: We will search eight databases from their inception to the date before the review submission. Randomised controlled trials (RCTs) will be included. Two reviewers will independently extract data using a structured data extraction method and assess the risk of bias in the included studies. Data will be synthesised using standardised mean difference or risk ratio with 95% CIs for continuous and dichotomous data, respectively. The primary outcome will be change in pain and secondary outcomes will include global symptom improvement, functional impairment and disability, impairment of sensation, quality of life, nerve conduction, and adverse events. Sensitivity and subgroup analysis will be employed to explore the influence of possible clinical and methodological characteristics. Publication bias will be assessed using funnel plot. We will conduct meta-analysis with RevMan V.5.4 and evaluate quality of the evidence using GRADE approach. ETHICS AND DISSEMINATION: This study does not require ethics approval. Our findings will be disseminated in the peer-reviewed publications. PROSPERO REGISTRATION NUMBER: CRD42021276056.

Effect of Modified Laser Transcutaneous Irradiation on Pain and Quality of Life in Patients with Diabetic Neuropathy.

Background: Diabetic neuropathy (DN) is one of the major complications developed by individuals with diabetes mellitus. DN is responsible for a high morbidity and mortality rate and impacts the public health and medical assistance resources. Intradermic laser irradiation on blood (ILIB) consists of the application of light beams on the radial arterial, providing anti-inflammatory and vasodilator effects, antiarrhythmic action, reduction of glucose, and stabilization of the hormonal and immunological systems. These effects help to maintain the physiological dynamics of the body. Objective: The goal of this research was to evaluate the effects of ILIB to relieve pain and improve the quality of life in DN patients. The sample comprised 30 diabetic volunteers with DN, randomly distributed into 3 groups: Control-conventional treatment; ILIB-100 mW, 660 ± 10 nm, 30 applications in total, divided into 3 stages of 10 applications, 30 min each, daily, with a 20-day interval between each stage; SILIB-same protocol described for ILIB, with the equipment switched off. Before and after the application of the therapeutic protocols, all volunteers were evaluated by the following instruments: Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), visual analog scale, Leeds Assessment of Neuropathic Symptoms and Signs (LANSS), and PAIN DETECT scale. Collected data were statistically analyzed with a 95% confidence interval, p < 0.05. Results: The ILIB group presented significantly lower pain levels and a better quality of life compared with the control and SILIB groups. Conclusions: This study demonstrated that ILIB therapy was effective in reducing pain and improving quality of life in patients with DN.

Photobiomodulation increases cell viability via AKT activation in an in vitro model of diabetes induced by glucose neurotoxicity.

Peripheral neuropathy (PN) is a serious complication of diabetes mellitus (DM) and is known to be resistant to conventional treatment. Photobiomodulation (PBM) is demonstrated to be effective in treating PN and in protecting nerve fiber damage. To better understand the mechanisms underlying the regenerative effects of PBM on diabetic neuropathy, we conducted a study in an in vitro model of diabetes induced by glucose neurotoxicity. Neuro 2A cells (1 × 104 cells/ well; N2A) were cultured in Minimum Essential Medium (MEM) supplemented with high glucose concentrations (100 mM) for 48 h and after the incubation period were submitted to either one or three consecutive applications of PBM, once a day (low-level InGaAlP, continuous wave mode, 660 nm, 30 mW, 1.6 J/cm2, 15 s, per well). Cell viability was measured by MTT method, neurotoxicity by LDH release, neurite outgrowth was evaluated through morphometric analysis, and AKT/ERK protein expression levels were assessed by western blotting. Results demonstrate that PBM increased N2A viability as well as induced neurogenesis observed by the increase in neurite outgrowth being this effect modulated by AKT activation. Data obtained herein reinforce the regenerative potential of PBM in the treatment of PN and strongly suggests that phototherapy should be considered adjuvant in the treatment of diabetes.

Effect of Low Level Laser Therapy on serum vitamin D and magnesium levels in patients with diabetic peripheral neuropathy - A pilot study.

BACKGROUND: Diabetic Peripheral neuropathy (DPN) is the most distressing complication of diabetic population leading to loss of sensation, pain, and amputation. Low-level laser therapy (LLLT) has been used to manage nerve injuries as it holds the potential to induce a biostimulatory effect with no side effects. Hence we planned to study the biochemical effect and therapeutic outcomes of LLLT on patients with painful diabetic peripheral neuropathy as a preliminary work. MATERIALS AND METHODS: Pre-posttest analysis was done on 40 patients diagnosed with DPN confirmed using 10 g Monofilament test and Michigan Neuropathy Screening Instrument (MNSI). Vibration sensation and pain measured by Vibration perception threshold (VPT) and Numeric pain rating scale (NPRS). All patients were given LLLT (3.1 J/cm2) on plantar and dorsal of the foot for 10 days. Serum samples were collected at baseline and 4 weeks after LLLT to estimate Vitamin D and Magnesium and compared the results. RESULTS: There was a significant increase in Vitamin D and Magnesium levels after LLLT. We observed a considerable improvement in the quality of life after LLLT demonstrated by a decrease in VPT and MNSI and a reduction in NPRS in DPN patients. CONCLUSION: In this study, we found that LLLT improved the QL and hence may be a useful therapeutic option in treating peripheral neuropathic pain in type 2 diabetic patients. The progress in the serum Magnesium and Vit. D levels were proportional to the QL and may be a good indicator of the prognosis of DPN after LLLT.

Influence of low-level laser on pain and inflammation in type 2 diabetes mellitus with diabetic dermopathy - A case report.

Numerous skin lesions have been commonly observed in individuals with diabetes mellitus. The common skin manifestations of diabetes mellitus are erythrasma, xanthomatosis, xanthelasma, phycomycetes and cutaneous infections like furuncolosis, candidiasis, carbuncle, dermatophytosis, etc. Diabetic dermopathy is the most common skin lesion found in patients with diabetes. It is typically seen in men aged above 50 years. In low-level laser therapy (LLLT), the entire lower limb was illuminated with the frequency of 20 Hz and wavelength of 830 nm for 9 min, and the treatment was divided into four parts. With the continued sessions of LLLT, the skin manifestations and neuropathy conditions improved drastically. On the 21st day, the skin colour was found to be normal. Also, there were significant changes in clinical findings for diabetic peripheral neuropathy. LLLT with specific exercises can promote healing of skin manifestations in individuals with type 2 diabetes mellitus. It can be used as an effective treatment modality for treating diabetic dermopathy.

Photobiostimulation reverses allodynia and peripheral nerve damage in streptozotocin-induced type 1 diabetes.

For better evaluation of the efficacy of low-level laser therapy in treating painful diabetic neuropathy and in protecting nerve fiber damage, we conducted a study with type 1 diabetic rats induced by streptozotocin. It is well known that diabetic peripheral neuropathy is the leading cause of pain in those individuals who suffer from diabetes. Despite the efficacy of insulin in controlling glucose level in blood, there is no effective treatment to prevent or reverse neuropathic damage for total pain relief.Male Wistar rats were divided into saline, vehicle, and treatment groups. A single intraperitoneal (i.p.) injection of streptozotocin (STZ) (85 mg/kg) was administered for the induction of diabetes. The von Frey filaments were used to assess nociceptive thresholds (allodynia). Behavioral measurements were accessed 14, 28, 48, and 56 days after STZ administration. Rats were irradiated with GaAs Laser (Gallium Arsenide, Laserpulse, Ibramed Brazil) emitting a wavelength of 904 nm, an output power of 45 mWpk, beam spot size at target 0.13 cm2, a frequency of 9500 Hz, a pulse time 60 ns, and an energy density of 6,23 J/cm2.The application of four sessions of low-level laser therapy was sufficient to reverse allodynia and protect peripheral nerve damage in diabetic rats.The results of this study indicate that low-level laser therapy is feasible to treat painful diabetic condition in rats using this protocol. Although its efficacy in reversing painful stimuli and protecting nerve fibers from damage was demonstrated, this treatment protocol must be further evaluated in biochemical levels to confirm its biological effects.

Effects of monochromatic infrared energy therapy on diabetic feet with peripheral sensory neuropathy: a randomised controlled trial.

INTRODUCTION: Peripheral diabetic neuropathy, which is a cause of increasing morbidity and mortality following foot ulcers and amputations, is a burden to health and the economy. Various adjunct treatments to improve neuropathy have been introduced into the market; one such treatment is monochromatic infrared energy (MIRE) therapy, which claimed to produce promising results. This study aimed to evaluate the effects of MIRE on diabetic feet with peripheral neuropathy. METHODS: A randomised controlled, single-blinded study was conducted at Hospital Universiti Sains Malaysia from February 2008 to October 2008. A total of 30 feet from 24 patients were studied. Neuropathy was screened using the Michigan neuropathy scoring instrument, followed by an assessment of the current perception threshold using a neurometer at frequencies of 2,000 Hz, 250 Hz and 5 Hz. The feet were randomised to receive either daily MIRE or sham treatment for a total of 12 treatments. Each foot was then reassessed using the neurometer at six weeks and three months following treatment. RESULTS: The data obtained was analysed using a non-parametric test to compare the pre- and post-treatment groups. No significant difference was found between the neuropathic foot of diabetic patients in both the MIRE and sham groups. CONCLUSION: No improvement of neuropathy was observed following MIRE treatment in the neuropathic feet of diabetic patients.

Diabetic distal symmetric polyneuropathy: effect of low-intensity laser therapy.

Low-intensity laser therapy (LILT) has been considered as a treatment modality in diabetic distal symmetric polyneuropathy (DSP). The aim of this study is to determine the effectiveness of LILT on DSP. We examined 107 subjects with type 2 diabetes for detection of DSP using the Michigan Neuropathy Screening Instrument (MNSI). Seventeen subjects were eligible to be enrolled in the study. Nerve conduction studies (NCS) were performed in all eligible subjects as an objective method to confirm neuropathy. The participants received LILT three times a week for ten sessions. NCSs were reevaluated after completion of the treatment. The absolute changes in NCS parameters were considered to establish the effectiveness of the treatment. Baseline demographics were similar in all participants. The mean differences of NCV parameters were considered for comparison. At the end of the study, the subjects showed a significant increase in neural potential amplitudes (p < 0.05). This study clearly demonstrated a significant positive effect of LILT on improvement of nerve conduction velocity on diabetic distal symmetric polyneuropathy (DSP). This finding supports the therapeutic potential of LILT in DSP.

Effect of optically modified polyethylene terephthalate fiber socks on chronic foot pain.

BACKGROUND: Increasing experimental and clinical evidence suggests that illumination of the skin with relatively low intensity light may lead to therapeutic results such as reduced pain or improved wound healing. The goal of this study was to evaluate prospectively whether socks made from polyethylene terephthalate (PET) incorporating optically active particles (Celliant) ameliorates chronic foot pain resulting from diabetic neuropathy or other disorders. Such optically modified fiber is thought to modify the illumination of the skin in the visible and infrared portions of the spectrum, and consequently reduce pain. METHODS: A double-blind, randomized trial with 55 subjects (38 men, 17 women) enrolled (average age 59.7 +/- 11.9 years), 26 with diabetic neuropathy and 29 with other pain etiologies. Subjects twice completed the Visual Analogue Scale (VAS), Brief Pain Inventory (BPI), McGill Pain Questionnaire (MPQ), and SF-36 a week apart (W(1+2)) before receiving either control or Celliant socks. The same questionnaires were answered again one and two weeks (W(3+4)) later. The questionnaires provided nine scores for analyzing pain reduction: one VAS score, two BPI scores, five MPQ scores, and the bodily pain score on the SF-36. Mean W(1+2) and W(3+4) scores were compared to measure pain reduction. RESULTS: More pain reduction was reported by Celliant subjects for 8 of the 9 pain questions employed, with a significant (p = 0.043) difference between controls and Celliant for McGill question III. In neuropathic subjects, Celliant caused more pain reduction in 6 of the 9 questions, but not significantly. In non-neuropathic subjects 8 of 9 questions showed more pain reduction with the Celliant socks. CONCLUSION: Socks with optically modified PET (Celliant) appear to have a beneficial impact on chronic foot pain. The mechanism could be related to the effects seen with illumination of tissues with visible and infrared light. TRIAL REGISTRATION: ClinicalTrials.gov NCT00458497.

Does anodyne light therapy improve peripheral neuropathy in diabetes? A double-blind, sham-controlled, randomized trial to evaluate monochromatic infrared photoenergy.

OBJECTIVE: The purpose of this study was to determine the efficacy of anodyne monochromatic infrared photo energy (MIRE) in-home treatments over a 90-day period to improve peripheral sensation and self-reported quality of life in individuals with diabetes. RESEARCH DESIGN AND METHODS: This was a double-blind, randomized, sham-controlled clinical trail. We randomly assigned 69 individuals with diabetes and a vibration perception threshold (VPT) between 20 and 45 V to two treatment groups: active or sham treatment. Sixty patients (120 limbs) completed the study. Anodyne units were used at home every day for 40 min for 90 days. We evaluated nerve conduction velocities, VPT, Semmes-Weinstein monofilaments (SWM) (4-, 10-, 26-, and 60-g monofilaments), the Michigan Neuropathy Screening Instrument (MNSI), a 10-cm visual analog pain scale, and a neuropathy-specific quality of life instrument. We used a nested repeated-measures multiple ANOVA design. Two sites (great toe and fifth metatarsal) were tested on both the left and right feet of each patient, so two feet were nested within each patient and two sites were nested within each foot. To analyze the ordinal SWM scores, we used a nonparametric factorial analysis for longitudinal data. RESULTS: There were no significant differences in measures for quality of life, MNSI, VPT, SWM, or nerve conduction velocities in active or sham treatment groups (P > 0.05). CONCLUSIONS: Anodyne MIRE therapy was no more effective than sham therapy in the treatment of sensory neuropathy in individuals with diabetes.

[Influence of low-intensity laser therapy on spatial perception threshold and electroneurographic finding in patients with diabetic polyneuropathy].

INTRODUCTION: Low-intensity laser therapy (LILT) can be applied in cases when patients with diabetic polyneuropathy (DPN) suffer from chronic severe neuropathic pain. OBJECTIVE: We wanted to analyse influence of LILT on spatial perception threshold (SPT) and electroneurographic (ENG) parameters in patients with painful DPN. METHOD: We analysed 45 patients (25 males), average age 54.3 years (54.3 +/- 10.9), with clinical and ENG signs of painful DPN. The patients were divided into two groups: A and B. Group A consisted of 30 patients with DPN who had 30 LILT treatments over the period of 12 weeks and group B consisted of 15 patients with DPN who received only vitamin therapy per os within the same period. Prior to and after 12 weeks of treatment, the following ENG parameters were determined using surface electrodes: motor (MCV) and sensory conduction velocities (SCV) values (in m/s) of nervus (n.) peroneus (NP), n. tibialis (NT) and n. medianus (NM) and their motor distal latency (MDL) values (in ms). SPT value (score as number from 1 to 8) was determined with Tactile Circumferential Discriminator on dorsal part of foot's big toe skin. For statistical analysis, we used Student's t-test and Pearson correlation (sig. 2 tailed) study. RESULTS; We registered statistically significant difference between SPT (p < 0.01) values prior to (5.25 +/- 1.11) and after (4.87 +/- 0.90) LILT, as well as NMMCV (p < 0.05) values prior to (47.18 +/- 5.08) and after (49.12 +/- 3.72) LILT. Besides, we registered, only after LILT, statistically significant correlation beetwen SPT and NMDML (p < 0.01) values and also beetwen SPT and NMSCV (p < 0.05) values. The differences and correlations beetwen other analysed parameters before and after treatments were not significant (p > 0.05). CONCLUSION: In this study we registered significant decrease of SPT and increase of NMMCV after LILT and that indicated a favourable effect of this treatment in analysed patients with painful DPN. In our opinion these results need further investigation.

The restorative effects of pulsed infrared light therapy on significant loss of peripheral protective sensation in patients with long-term type 1 and type 2 diabetes mellitus.

Pulsed infrared light therapy (PILT) has been shown to increase peripheral sensation in diabetic patients with diabetic peripheral neuropathy (DPN). However, most studies last for very short periods, with the subjects receiving only 6-20 treatments. The purpose of this study was to evaluate the effectiveness of an eight-week course of PILT in reversing long-standing, profound DPN in patients with type 1 and type 2 diabetes. Twenty-two subjects with a diagnosis of type 1 (n=2) or type 2 (n=20) diabetes participated in the study. PILT was administered to one foot chosen at random with the other foot serving as a within-subject control (no treatment). Patients underwent 24 treatments (3 times/week, for eight weeks) for 30 min per treatment. Changes in peripheral protective sensation (PPS) were measured using Semmes-Weinstein monofilaments (SWM) ranging from 3.7 to 6.48. PILT improved PPS even in patients with long-standing chronic neuropathies whose initial pre-study sensation was not measurable with a 200-g SWM. PILT significantly improves PPS. While the exact mechanism of action is not understood, infrared light may improve peripheral neuropathies by improving foot perfusion by stimulating nitric oxide production.

Low-intensity laser therapy for painful symptoms of diabetic sensorimotor polyneuropathy: a controlled trial.

OBJECTIVE: Low-intensity laser therapy (LILT) has been advocated for treatment of chronic pain disorders. Although the mechanism of pain relief is uncertain, this therapy has been suggested for relief of painful symptoms of diabetic sensorimotor polyneuropathy (DSP). The objective of this study was to determine whether LILT relieves the pain of DSP. RESEARCH DESIGN AND METHODS: We conducted a randomized, double-masked, sham therapy-controlled clinical trial in 50 patients with painful DSP diagnosed with the Toronto Clinical Neuropathy Score. All patients received sham therapy over a 2-week baseline period and were then randomized to receive biweekly sessions of either sham or LILT for 4 weeks. The primary efficacy parameter was the difference in the weekly mean pain scores on a visual analog scale (VAS). RESULTS: The patients had similar baseline characteristics for pain intensity, HbA(1c), and duration of DSP. Both groups noted a decrease in weekly mean pain scores during sham treatment. After the 4-week intervention, the LILT group had an additional reduction in weekly mean pain scores of -1.0 +/- 0.4 compared with -0.0 +/- 0.4 for the sham group (P = 0.07). LILT had no effect on the Toronto Clinical Neuropathy Score, nerve conduction studies, sympathetic skin response, or quantitative sensory testing. CONCLUSIONS: Although an encouraging trend was observed with LILT, the study results do not provide sufficient evidence to recommend this treatment for painful symptoms of DSP.

[Use of physical factors in the complex therapy of patients with diabetic angio- and polyneuropathies of the lower extremities]. / Primenenie fizicheskikh faktorov v kompleksnom lechenii bol'nykh s angio- i polinevropatiei nizhnikh konechnostei.

Results are submitted of treatment of 110 patients with diabetes mellitus (61 male and 49 female subjects) presenting with angio- and polyneuropathies of the lower extremities. 70 patients, in addition to a drug therapy, were administered physiotherapeutic treatments, such as amplipulsetherapy, darsonvalization, and laserotherapy. Forty patients received medicamentous therapy only. Based on clinical findings and laboratory methods of investigation expediency has been shown of employment of physiotherapeutic methods in the treatment of the above pathology.

[Laser therapy in diabetes mellitus]. / Lazeroterapiia pry tsukrovomu diabeti.

Diabetic patients have been shown to derive great benefit from treatment with laser therapy as evidenced by experience gained with its use over many years. Laser therapy promotes compensation, has an antiatherogenic, antioxidant, immunomodulating effects, improves microcirculation, myocardial contractility and performance capability.

[Infrared laser therapy in distal diabetic polyneuropathy]. / Infrakrasnaia lazeroterapiia pri distal'noi diabeticheskoi polinevropatii.

A course of laser therapy was applied to 50 patients with diabetic polyneuropathy by laser irradiation of low intensiveness in the nearest infrared spectrum. 20 patients from the group were treated by monotherapy only by laser exposure. Control group consisted of 24 patients treated by conventional therapy without laser exposure. According to the changes of vibratory and algesic sensitivity and electromyographic data the efficiency of therapy was estimated. It was found that laser exposure resulted in more pronounced restoration of functional state of nervous fibers than conventional therapy. Application of laser irradiation of low intensiveness was effective while in combined therapy of distal diabetic polyneuropathy as well as monotherapy.