Improvement In Nerve Conduction Velocity Research Articles

Effect of the glucagon-like peptide-1 receptor agonists on diabetic peripheral neuropathy: A meta-analysis.

Previous researches found that glucagon-like peptide 1 receptor agonists (GLP-1RA) offer benefits beyond their anti-diabetic properties, including weight loss and cardiovascular disease prevention. However, the effects of GLP-1RA on diabetic peripheral neuropathy (DPN) remain unclear. This meta-analysis aims to assess the potential benefits of GLP-1RA treatment in DPN patients by evaluating peripheral neural function. Following the Cochrane Collaboration and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a meta-analysis of the clinical trials investigating the impact of GLP-1RA treatment on peripheral neural function in patients with DPN. Outcomes were measured using electrophysiological tests, including nerve conduction velocity (NCV) and action potential amplitude. Our meta-analysis included six studies with 271 participants. Following GLP-1RA treatment, NCV significantly improved compared to the control group (MD 1.74; 95% CI 1.16 to 2.33; p < 0.001) and before treatment (MD 2.16; 95% CI 1.04 to 3.27; p < 0.001). Despite the improvement in NCV, blood glucose levels did not change significantly (MD -0.20 95% CI -0.87 to 0.46, p = 0.55) indicating that GLP-1RA enhances NCV through mechanisms other than glucose lowering. Nonetheless, as a result of the limited population studied, further research is needed to strengthen the reliability of these findings.

Tangzu granule alleviate neuroinflammation in diabetic peripheral neuropathy by suppressing pyroptosis through P2X7R /NLRP3 signaling pathway

Ethnopharmacological relevanceDiabetic peripheral neuropathy (DPN) is a common complication of diabetes mellitus, mainly manifested as paresthesia. Tangzu granule (TZG) is derived from famous traditional Chinese medicine decoctions and optimized by long-term temporary practice. TZG has good efficacy in improving numbness, pain and pruritus of the lower extremities of DPN patients. However, the overall regulatory mechanisms underlying its effects on DPN remain unclear. Aim of the studyThis study aims to explore the potential mechanism of TZG for treating DPN. Materials and methodsSprague-Dawley (SD) rats were used to establish an in vivo model of DPN with streptozotocin (STZ) injection and high-fat diet (HFD) feeding. Additionally, sciatic glial RSC96 cells were induced with high glucose in vitro. SD rats in intervention group received TZG treatment for 12 weeks. After 12 weeks of treatment, sciatic nerve function was evaluated by intelligent hot plate meter and neuro electrophysiology detector. The morphological changes of sciatic nerve cells were observed by hematoxylin-eosin staining and transmission electron microscope. IL-1β, IL-18 inflammatory cytokines, pyroptosis and P2X7R/NLRP3 signaling pathway were observed by Western blotting, immunofluorescence staining and ELISA. ResultsTZG improved nerve conduction velocity and sciatic neuropathy rational structural changes in DPN rats. It also inhibited RSC96 inflammatory response and cell death that induced by high glucose. This may be related to TZG inhibiting P2X7R, decreasing the activation of NLRP3 inflammasomes, down-regulating the levels of pyroptosis proteins such as caspase-1, cleaved caspase-1, gasdermin D (GSDMD), and GSDMD-N, and inhibiting the release of interleuki (IL)-18 and IL-1β inflammatory cytokines. ConclusionsTZG inhibited pyroptosis through P2X7R/NLRP3 signaling pathway, alleviated neuroinflammation, and showed protective effect in the treatment of DPN.

Alleviated diabetic osteoporosis and peripheral neuropathic pain by Rehmannia glutinosa Libosch polysaccharide via increasing regulatory T cells

Diabetic peripheral neuropathy (DPN) and diabetic osteoporosis (DOP) are conditions that significantly impact the quality of life of patients worldwide. Rehmanniae Radix Preparata, a component of traditional Chinese medicine with a history spanning thousands of years, has been utilized in the treatment of osteoporosis and diabetes. Specifically, Rehmannia glutinosa Libosch polysaccharide (RGP), a key bioactive compound of Rehmanniae Radix Preparata, has demonstrated immune-modulating properties and beneficial effects on hyperglycemia, hyperlipidemia, and vascular inflammation in diabetic mice. Despite these known actions, the precise mechanisms of RGP in addressing DOP and DPN remain unclear. Our study aimed to explore the impact of RGP on osteoporosis and peripheral neuropathic pain in diabetic mice induced by streptozotocin (STZ). The findings revealed that RGP not only improved hyperglycemia and osteoporosis in STZ-induced diabetic mice but also enhanced osteogenesis, insulin production, and nerve health. Specifically, RGP alleviated distal pain, improved nerve conduction velocity, nerve fiber integrity, and immune cell balance in the spleen. Mechanistically, RGP was found to upregulate HDAC6 mRNA expression in regulatory T cells, potentially shedding light on novel pathways for preventing DOP and DPN. These results offer promising insights for the development of new therapeutic approaches for diabetic complications.

Effect of flipped venous catheter combined with spinal cord electrical stimulation on functional recovery in patients with sciatic nerve injury.

This study aimed to explore the effect of flipped venous catheters combined with spinal cord electrical stimulation on functional recovery in patients with sciatic nerve injury. 160 patients with hip dislocation and sciatic nerve injury were divided into conventional release and flipped catheter + electrical stimulation groups according to the treatment methods (n=80). Motor nerve conduction velocity (MCV) and lower limb motor function were compared. Serum neurotrophic factors brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) were compared. The frequency of complications and quality of life were also compared. The MCV levels of the common peroneal nerve and tibial nerve in the flipped catheter + electrical stimulation group were greater than the conventional lysis group (p<0.05). After treatment, the lower extremity motor score (LMEs) in the flipped catheter + electrical stimulation group was greater than the conventional lysis group (p<0.05). The serum levels of BDNF and NGF in the flip catheter + electrical stimulation group were higher than the conventional lysis group (p<0.05). The complication rate in the flipped catheter + electrical stimulation group was lower than in the conventional release group (6.25% vs. 16.25%, p<0.05). The quality-of-life score in the flip catheter + electrical stimulation group was greater than the conventional lysis group (p<0.05). The flipped venous catheter combined with spinal cord electrical stimulation can improve nerve conduction velocity, lower limb motor function, serum BDNF and NGF levels, reduce complications, and help improve the quality of life of sufferers with sciatic nerve injury. Chictr.org.cn ID: ChiCTR2400080984.

Systematic review of translational insights: Neuromodulation in animal models for Diabetic Peripheral Neuropathy.

Diabetic Peripheral Neuropathy (DPN) is a prevalent and debilitating complication of diabetes, affecting a significant proportion of the diabetic population. Neuromodulation, an emerging therapeutic approach, has shown promise in the management of DPN symptoms. This systematic review aims to synthesize and analyze the current advancements in neuromodulation techniques for the treatment of DPN utilizing studies with preclinical animal models. A comprehensive search was conducted across multiple databases, including PubMed, Scopus, and Web of Science. Inclusion criteria were focused on studies utilizing preclinical animal models for DPN that investigated the efficacy of various neuromodulation techniques, such as spinal cord stimulation, transcranial magnetic stimulation, and peripheral nerve stimulation. The findings suggest that neuromodulation significantly alleviated pain symptoms associated with DPN. Moreover, some studies reported improvements in nerve conduction velocity and reduction in nerve damage. The mechanisms underlying these effects appeared to involve modulation of pain pathways and enhancement of neurotrophic factors. However, the review also highlights the variability in methodology and stimulation parameters across studies, highlighting the need for standardization in future research. Additionally, while the results are promising, the translation of these findings from animal models to human clinical practice requires careful consideration. This review concludes that neuromodulation presents a potentially effective therapeutic strategy for DPN, but further research is necessary to optimize protocols and understand the underlying molecular mechanisms. It also emphasizes the importance of bridging the gap between preclinical findings and clinical applications to improve the management of DPN in diabetic patients.

Repeat intramuscular transplantation of human dental pulp stromal cells is more effective in sustaining Schwann cell survival and myelination for functional recovery after onset of diabetic neuropathy

Background aimsMesenchymal stromal cell (MSC) therapy for diabetic neuropathy (DN) has been extensively researched in vitro and in pre-clinical studies; however, the clinical scenario thus far has been disappointing. Temporary recovery, a common feature of these studies, indicates that either the retention of transplanted cells deteriorates with time or recovery of supportive endogenous cells, such as bone marrow-derived MSCs (BM-MSCs), does not occur, requiring further replenishment. In DN, BM-MSCs are recognized mediators of Schwann cell regeneration, and we have earlier shown that they suffer impairment in the pre-neuropathy stage. In this study, we attempted to further elucidate the mechanisms of functional recovery by focusing on changes occurring at the cellular level in the sciatic nerve, in conjunction with the biodistribution and movement patterns of the transplanted cells, to define the interval between doses. Method & ResultsWe found that two doses of 1 × 106 dental pulp stromal cells (DPSCs) transplanted intramuscularly at an interval of 4 weeks effectively improved nerve conduction velocity (NCV) and restored motor coordination through improving sciatic nerve architecture, Schwann cell survival and myelination. Despite very minimal recovery of endogenous BM-MSCs, a temporary restoration of NCV and motor function was achieved with the first dose of DPSC transplantation. However, this did not persist, and a repeat dose was needed to consolidate functional improvement and rehabilitate the sciatic nerve architecture. ConclusionThus, repeat intramuscular transplantation of DPSCs is more effective for maintenance of Schwann cell survival and myelination for functional recovery after onset of DN.

The role of ultrasound-guided perineural injection of the tibial nerve with a sub-anesthetic dosage of lidocaine for the diagnosis of tarsal tunnel syndrome.

Tarsal tunnel syndrome (TTS) involves entrapment of the tibial nerve at the medial ankle beneath the flexor retinaculum and its branches, the medial and lateral plantar nerves, as they course through the porta pedis formed by the deep fascia of the abductor hallucis muscle. TTS is likely underdiagnosed, because diagnosis is based on clinical evaluation and history of present illness. The ultrasound-guided lidocaine infiltration test (USLIT) is a simple approach that may aid in the diagnosis of TTS and predict the response to neurolysis of the tibial nerve and its branches. Traditional electrophysiological testing cannot confirm the diagnosis and only adds to other findings. We performed a prospective study of 61 patients (23 men and 38 women) with a mean age of 51 (29-78) years who were diagnosed with idiopathic TTS using the ultrasound guided near-nerve needle sensory technique (USG-NNNS). Patients subsequently underwent USLIT of the tibial nerve to assess the effect on pain reduction and neurophysiological changes. USLIT led to an improvement in symptoms and nerve conduction velocity. The objective improvement in nerve conduction velocity can be used to document the pre-operative functional capacity of the nerve. USLIT may also be used as a possible quantitative indicator of whether the nerve has the potential to improve in neurophysiological terms and ultimately inform prognosis after surgical decompression. USLIT is a simple technique with potential predictive value that can help the clinician to confirm the diagnosis of TTS before surgical decompression.

SIRT1-Enriched Exosomes Derived from Bone Marrow Mesenchymal Stromal Cells Alleviate Peripheral Neuropathy via Conserving Mitochondrial Function.

Diabetic peripheral neuropathy (DPN) is a highly prevalent diabetic complication characterized at the molecular level by mitochondrial dysfunction and deleterious oxidative damage. No effective treatments for DPN are currently available. The present study was developed to examine the impact of exosomes derived from bone marrow mesenchymal stromal cells (BMSCs) overexpressing sirtuin 1 (SIRT1) on DPN through antioxidant activity and the preservation of mitochondrial homeostasis. A DPN model was established using 20-week-old diabetic model mice (db/db). Exosomes were prepared from control BMSCs (exo-control) and BMSCs that had been transduced with a SIRT1 lentivirus (exo-SIRT1). Sensory and motor nerve conduction velocity values were measured to assess neurological function, and mechanical and thermal sensitivity were analyzed in these animals. Exo-SIRT1 preparations exhibited a high loading capacity and readily accumulated within peripheral nerves following intravenous administration, whereupon they were able to promote improved neurological recovery relative to exo-control treatment. DPN mice exhibited significantly improved nerve conduction velocity following exo-SIRT1 treatment. Relative to exo-control-treated mice, those that underwent exo-SIRT1 treatment exhibited significantly elevated TOMM20 and Nrf2/HO-1 expression, reduced MDA levels, increased GSH and SOD activity, and increased MMP. Together, these results revealed that both exo-control and exo-SIRT1 administration was sufficient to reduce the morphological and behavioral changes observed in DPN model mice, with exo-SIRT1 treatment exhibiting superior therapeutic efficacy. These data thus provide a foundation for future efforts to explore other combinations of gene therapy and exosome treatment in an effort to alleviate DPN.

The effectiveness and safety of acupuncture/electroacupuncture for chemotherapy-induced peripheral neuropathy: a systematic review and meta-analysis.

Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting adverse effect of anticancer agents with virtually no effective treatment. Safe and effective therapies are needed urgently. Acupuncture shows therapeutic possibilities in this regard but needs to be further evaluated. A systematic search was conducted in seven databases from their inception to April 2020. Randomized controlled trials (RCTs) focused on acupuncture/electroacupuncture (EA) for the treatment of CIPN were included. Revman 5.3 software was used for meta-analysis if there was no significant heterogeneity. Otherwise, qualitative analysis was utilized. Nine studies involving 582 patients were included in this review. Most of the studies exhibited unclear risk of bias because some details were not mentioned. As the clinical heterogeneity was significant, qualitative analysis was performed to describe nerve conduction velocity, effective rate for motor neuropathy, pain scores, quality of life and adverse events. Meta-analysis was performed on four studies to analyze the effective rate for sensory neuropathy due to inconspicuous heterogeneity. The results indicated that acupuncture may generate a better effect on sensory neuropathy than vitamin B (risk ratio = 1.60, 95% confidence interval = 1.31-1.95, I2 = 0%, p < 0.00001). The efficacy of EA plus glutathione (GSH) appeared to be better than that of GSH alone in alleviating sensory neurotoxicity and in improving nerve conduction velocity. Acupuncture plus methylcobalamin showed more favorable effects than methylcobalamin alone in relieving neuralgia, restoring nerve conduction velocity and improving quality of life. In terms of pain relief and improved CIPN-specific quality of life, acupuncture plus standard care was better than standard care alone. In terms of pain relief, EA was more effective than usual care. Acupuncture may be effective and safe in the treatment of CIPN according to the analyzed studies. However, more studies with higher methodological quality are warranted in order to be able to draw firmer conclusions. Future rigorous RCTs will be necessary to confirm the effectiveness and safety of acupuncture for CIPN.

Comparison of Two Manual Therapy Programs, including Tendon Gliding Exercises as a Common Adjunct, While Managing the Participants with Chronic Carpal Tunnel Syndrome.

Background Carpal tunnel syndrome (CTS) is the symptomatic compression neuropathy of the median nerve at the wrist level that may become a reason for upper limb disability, in the women and men population. Objective This study aimed to compare the efficacy of the neurodynamic technique (NT) and carpal bone mobilization technique (CBMT) incorporated with tendon gliding exercises (TGE) as an effect-enhancing adjunct while managing the participants with chronic CTS. Methods The study followed a two-arm parallel-group randomized comparative design. Thirty participants (aged 30–59 years) with chronic CTS were recruited randomly to both the NT and CBMT groups. In addition to the TGE (a common adjunct), NT and CBMT were performed in the NT and CBMT groups, respectively, for three weeks. The primary outcome measures including pain intensity, functional status, grip strength, and motor nerve conduction study were assessed using a visual analogue scale (VAS), Boston Carpal Tunnel Questionnaire (BCTQ), hand-held dynamometer, and electromyograph, respectively, at baseline, 3 weeks postintervention, and follow-up at one week post end of the intervention. Paired and unpaired t-test were used to calculate the differences in intervention effects within and between the groups with keeping the level of significance α at 0.05. Results The data analysis revealed a significant (95% CI, p < 0.05) difference for all outcomes within each group compared across different time intervals. Similarly, a significant difference was found for all outcomes except pain and grip strength compared between groups at 3 weeks postintervention and follow-up at one week post end of the intervention. Conclusions The NT revealed more effectiveness than the CBMT when incorporated with TGE to improve nerve conduction velocity and functional status of the hand. However, both NT and CBMT were equally effective in improving pain and grip strength while managing the participants with chronic CTS. In addition, the TGE contributed as a beneficial, effect-enhancing adjunct to the NT and CBMT differently. Significance. The study will guide the physiotherapist in applying either of the combination techniques suitable for achieving treatment objectives while managing the participants with chronic CTS.

A Study on the Effect of 850 nm Low-Level Diode Laser versus Electrical Stimulation in Facial Nerve Regeneration for Patients with Bell’s Palsy

Introduction: Bell’s palsy is acute facial paralysis with unclear etiology that results in weakness of facial muscles or paralysis on one side of the face. Methods: This prospective, randomized, single-blind, controlled study was conducted on 45 patients with Bell’s palsy who were randomly divided into three equal groups. Two groups received either low-level laser therapy (LLLT) or electrical stimulation (E.S.) both in conjunction to medications, massage, and facial exercise treatment. The third group (control) was treated with medication, massage, and facial exercise. Results: The primary outcome was the improvement of nerve conduction velocity of facial nerve while the secondary outcome was the change of Sunnybrook facial grading system (SBGS). The outcome measures were evaluated pre- and posttreatment. There was statistically significant difference between the three groups in favor of the LLLT group regarding the nerve action potential amplitude and latency, in addition to signs of nerve regeneration and improved SBGS. Conclusion: This short-term investigation revealed that LLLT proved to be more efficient than E.S. in facial nerve regeneration for patients with Bell’s palsy.

Tocotrienol-Rich Vitamin E (Tocovid) Improved Nerve Conduction Velocity in Type 2 Diabetes Mellitus Patients in a Phase II Double-Blind, Randomized Controlled Clinical Trial

Diabetic peripheral neuropathy (DPN) is the most common microvascular complication of diabetes that affects approximately half of the diabetic population. Up to 53% of DPN patients experience neuropathic pain, which leads to a reduction in the quality of life and work productivity. Tocotrienols have been shown to possess antioxidant, anti-inflammatory, and neuroprotective properties in preclinical and clinical studies. This study aimed to investigate the effects of tocotrienol-rich vitamin E (Tocovid SuprabioTM) on nerve conduction parameters and serum biomarkers among patients with type 2 diabetes mellitus (T2DM). A total of 88 patients were randomized to receive 200 mg of Tocovid twice daily, or a matching placebo for 12 months. Fasting blood samples were collected for measurements of HbA1c, renal profile, lipid profile, and biomarkers. A nerve conduction study (NCS) was performed on all patients at baseline and subsequently at 2, 6, 12 months. Patients were reassessed after 6 months of washout. After 12 months of supplementation, patients in the Tocovid group exhibited highly significant improvements in conduction velocity (CV) of both median and sural sensory nerves as compared to those in the placebo group. The between-intervention-group differences (treatment effects) in CV were 1.60 m/s (95% CI: 0.70, 2.40) for the median nerve and 2.10 m/s (95% CI: 1.50, 2.90) for the sural nerve. A significant difference in peak velocity (PV) was also observed in the sural nerve (2.10 m/s; 95% CI: 1.00, 3.20) after 12 months. Significant improvements in CV were only observed up to 6 months in the tibial motor nerve, 1.30 m/s (95% CI: 0.60, 2.20). There were no significant changes in serum biomarkers, transforming growth factor beta-1 (TGFβ-1), or vascular endothelial growth factor A (VEGF-A). After 6 months of washout, there were no significant differences from baseline between groups in nerve conduction parameters of all three nerves. Tocovid at 400 mg/day significantly improve tibial motor nerve CV up to 6 months, but median and sural sensory nerve CV in up to 12 months of supplementation. All improvements diminished after 6 months of washout.

Astragaloside IV Inhibits Mitochondrial-Dependent Apoptosis of the Dorsal Root Ganglion in Diabetic Peripheral Neuropathy Rats Through Modulation of the SIRT1/p53 Signaling Pathway.

PurposeTo investigate the effect of astragaloside IV (AS-IV) on mitochondrial-dependent apoptosis in the dorsal root ganglion of diabetic peripheral neuropathy (DPN) rats through the SIRT1/p53 pathway.MethodsDiabetic rat model was induced by high-carbohydrate/high-fat diet and intraperitoneal injection of STZ. Diabetic rats were divided into three groups (n =16 per group): DPN group, AS-IV group (60mg/kg/d) and α-lipoic acid (ALA) group (60mg/kg/d). Weight and blood glucose levels were monitored every 4 weeks for 12 weeks. DPN was evaluated using the Von Frey Filaments Test and nerve conduction velocity. The dorsal root ganglia of rats were isolated and the pathological changes of mitochondria were observed by electron microscopy. The activity of mitochondrial electron transport chain complex, mitochondrial membrane potential, malonaldehyde (MDA) and glutathione (GSH) levels were measured. Neural apoptosis was detected using the Terminal Deoxynucleotidyl Nick-End Labeling (TUNEL) assay kit. The cleaved caspase-3, major proteins in the SIRT1/p53 pathway, including SIRT1, acetyl p53, Drp1, BAX, and BCL-2, were detected using immunohistochemistry and Western blot. Gene expression of major proteins in the SIRT1/p53 pathway was also detected.ResultsAfter 12 weeks of treatment, AS-IV and ALA did not significantly affect body weight or fasting glucose levels, but reduced mechanical abnormal pain in DPN and improved nerve conduction velocity. AS-IV and ALA increased the level of GSH and decreased the level of MDA. Both AS-IV and ALA can reduce mitochondrial damage, improve mitochondrial electron transport chain complex activity and mitochondrial membrane potential, and reduce the percentages of positive cells with DNA fragmentation and the expression of cleaved caspase-3 protein. AS-IV and ALA up-regulated the expression of SIRT1 and down-regulated the expression of acetyl-p53, Drp1 and the ratio of BAX to BCL-2. Changes in gene expression were similar.ConclusionAS-IV can reduce the occurrence of mitochondrial-dependent apoptosis by regulating the SIRT1/p53 pathway. It has a similar therapeutic effect as ALA and is therefore a promising drug for the potential treatment of DPN.

Pinpointing Problems: A Literature Review of Diabetic Peripheral Neuropathy

A subset of diabetic polyneuropathy, DPN is the most common neurological complication of diabetes. DPN affects around 12–50% of individuals with diabetes mellitus. DPN compromises the function of nerves in the hands, feet, legs, and arms. It is common for DPN to start in the feet, and often both feet are affected at once. This review of the literature seeks to summarize the current state of DPN research and key findings. &#x0D; Dissemination of community awareness about the diabetic foot may play a major role in managing DPN. Clinical tests for DPN are simple but lack a standardized approach for the quantification of pain and sensory loss. Thus, estimates of prevalence or intervention efficacy vary widely. Research into burden of disease focuses on ulceration, an ominous sign resulting in amputation and high morbidity/mortality. DPN increases the risk of fall, deteriorates mental health conditions, causes disability lowering quality of life. Specific research regarding the role of social determinants of health in DPN is lacking. It is clear, however, that race, low income, and lack of health insurance are associated with higher burden. Controlling blood glucose is highly effective in managing DPN. It can prevent DPN in Type 1 diabetes and can be effective for preventing DPN in Type 2 diabetes. Treatment of DPN is symptomatic and of limited efficacy in only a fraction of patients, relying primarily on antidepressants and anticonvulsants for the relief of pain. In management of DPN, exercise and psychological therapies can improve outcomes and improve nerve conduction velocity. Combined lifestyle interventions have shown success in prevention of microvascular complications of diabetes and ulceration and may be effective in DPN as well. Harmonization of quantitative diagnostic criteria and definitions of diabetic neuropathies would provide more useful endpoints for trials, epidemiological and mechanistic insight, and potential for earlier detection.

Studying the Effect of Adding Alpha Lipoic Acid to Gabapentin to Improve Nerve Conduction Velocity and Glycemic Control of Patients with Diabetic Neuropathy (Sample of Iraqi population)

Diabetic neuropathy (DN) is the most common chronic complication of diabetes mellitus. Hyperglycemia-induced oxidative stress induces programmed cell death of nerves, which contributes to the pathology of Diabetic neuropathy. Many clinical trials depend on supplement, in an attempt to improve neuropathy symptoms such as (pain &amp;&#x0D; &#x0D; tingling) and patient quality of life, one of them is alpha-lipoic acid (ALA). Alpha-lipoic acid is a potent anti-inflammatory and antioxidant with insulin-mimetic activity, it has been shown to improve clinical symptoms in experimental Diabetic neuropathy and protect peripheral nerves from ischemia, in addition to stimulate the nerve growth factor and promote fiber regeneration. This study is aimed to evaluate the effect of Alpha-lipoic acid supplement as adjuvant therapy to gabapentin in patients with diabetic neuropathy, which can reflect by the improvement in nerve conduction velocity (NCV) a test was conducted to assess the severity of iabetic neuropathy and clinical symptoms. A prospective randomized- open-label interventional study for 3 months include 33 DN patients, aged (18-69) years were divided into two groups; group A include 16 patients received gabapentin 300 mg once daily at night, and group B include 17 patients received gabapentin 300 mg once daily at night plus alpha-lipoic acid 600mg once daily. Pre and post 3 months of treatment, blood samples used to measure metabolic biomarkers (FBG, HbA1c), in addition to Nerve conduction velocity. The results showed that, the intervention group produced a highly significant change in HbA1c &amp; no significant change in FBG levels after 3months of Alpha-lipoic acid supplementation. Meanwhile, there is no significant change in HbA1c &amp; FBG levels in patients treated with gabapentin alone. Moreover, results showed highly significant improvement (P˂0.01) in Nerve conduction velocity for two groups at the end of the study. Addition of Alpha-lipoic acid to gabapentin in diabetic neuropathy patients result to improve the glycemic control &amp; Nerve conduction velocity.&#x0D; after three months of treatment.

Studying the Effect of Adding Alpha Lipoic Acid to Gabapentin to Improve Nerve Conduction Velocity and Glycemic Control of Patients with Diabetic Neuropathy (Sample of Iraqi population)

Diabetic neuropathy (DN) is the most common chronic complication of diabetes mellitus. Hyperglycemia-induced oxidative stress induces programmed cell death of nerves, which contributes to the pathology of Diabetic neuropathy. Many clinical trials depend on supplement, in an attempt to improve neuropathy symptoms such as (pain &amp; tingling) and patient quality of life, one of them is alpha-lipoic acid (ALA). Alpha-lipoic acid is a potent anti-inflammatory and antioxidant with insulin-mimetic activity, it has been shown to improve clinical symptoms in experimental Diabetic neuropathy and protect peripheral nerves from ischemia, in addition to stimulate the nerve growth factor and promote fiber regeneration. This study is aimed to evaluate the effect of Alpha-lipoic acid supplement as adjuvant therapy to gabapentin in patients with diabetic neuropathy, which can reflect by the improvement in nerve conduction velocity (NCV) a test was conducted to assess the severity of iabetic neuropathy and clinical symptoms. A prospective randomized- open-label interventional study for 3 months include 33 DN patients, aged (18-69) years were divided into two groups; group A include 16 patients received gabapentin 300 mg once daily at night, and group B include 17 patients received gabapentin 300 mg once daily at night plus alpha-lipoic acid 600mg once daily. Pre and post 3 months of treatment, blood samples used to measure metabolic biomarkers (FBG, HbA1c), in addition to Nerve conduction velocity. The results showed that, the intervention group produced a highly significant change in HbA1c &amp; no significant change in FBG levels after 3months of Alpha-lipoic acid supplementation. Meanwhile, there is no significant change in HbA1c &amp; FBG levels in patients treated with gabapentin alone. Moreover, results showed highly significant improvement (P˂0.01) in Nerve conduction velocity for two groups at the end of the study. Addition of Alpha-lipoic acid to gabapentin in diabetic neuropathy patients result to improve the glycemic control &amp; Nerve conduction velocity. after three months of treatment.

Autologous Bone Marrow Mononuclear Cell Transplantation Therapy Improved Symptoms in Patients with Refractory Diabetic Sensorimotor Polyneuropathy via the Mechanisms of Paracrine and Immunomodulation: A Controlled Study

We recently reported that transplantation of autologous bone marrow mononuclear cells (BM-MNCs) may be an effective and promising therapy to treat refractory diabetic sensorimotor polyneuropathy (DSPN) in patients with type 2 diabetes mellitus (T2DM). This study was designed to investigate the potential mechanisms of BM-MNCs therapy, which recruited 60 patients with DSPN, 30 T2DM patients without complications, and 30 healthy control participants. All clinical parameters, the levels of inflammatory markers, and growth factors in the three groups were compared. Patients in DSPN group had higher level of tumor necrosis factor-α (TNF-α) (DSPN vs control, 412.90 ± 64.58 vs 374.81 ± 63.18 pg/mL, P < 0.01) and lower level of vascular endothelial growth factor (VEGF) (DSPN vs control, 140.93 ± 24.78 vs 157.39 ± 25.11 pg/mL, P < 0.01) than those in control group. DSPN group had the highest level of soluble intercellular adhesion molecule-1 (sICAM-1) among three groups (DSPN and DM vs control, 1477.56 ± 228.00 and 1342.17 ± 237.54 vs 1308.00 ± 200.94 ng/mL, P < 0.05). The level of nerve growth factor in the DSPN group was slightly lower than that in the DM group (DSPN vs DM, 3509.11 ± 438.39 vs 3734.87 ± 647.50 pg/mL, P < 0.05). All patients with DSPN received one intramuscular injection of BM-MNCs and clinical follow-ups after the therapy for 2 days, 1, 4, 12, 24, and 48 weeks. Neuropathic symptoms of foot pain, numbness, and weakness were significantly improved within 4 weeks after BM-MNCs injection. Patients with DSPN were divided into the responder (n = 35) and nonresponder groups (n = 19) based on the improvement of nerve conduction velocity at 12 weeks post-transplantation. Compared with nonresponders, responders were younger (57.3 ± 5.2 vs 62.0 ± 4.8, P < 0.01), had a shorter history of diabetes (7.1 ± 2.7 vs 11.2 ± 5.4 years, P < 0.01), and had higher numbers of mobilized CD34+ cells (17.61 ± 2.64 vs 14.79 ± 1.62 ×105/L, P < 0.01) and BM-MNCs (12.05 ± 2.16 vs 9.84 ± 1.53 ×108/L, P < 0.01). The levels of TNF-α and sICAM-1 decreased just after BM-MNCs injection in both groups and slowly reverted to baseline levels. The duration of the downtrend of TNF-α and sICAM-1 in the responder group lasted longer than that in the nonresponder group. Serum level of VEGF in the responder group increased immediately after BM-MNC therapy and reached the highest point after the injection for 12 weeks. On the other hand, VEGF levels in the nonresponder group only increased slightly. Binary logistic regression was performed to evaluate the corresponding prognostic factors for BM-MNCs treatment. The number of applied CD34+ cells and the duration of diabetes were the independent predictors of responding to BM-MNCs therapy. No adverse event associated with the treatment was observed during follow-up observations. These results indicated that BM-MNCs transplantation is an effective and promising therapeutic strategy to treat refractory DSPN. The immune regulation and paracrine function of BM-MNCs may contribute to the improvement of DSPN. Trial registration: Chinese Clinical Trial Registry, ChiCTR-TRC-12002570. URL: http://www.chictr.org.cn/showproj.aspx?proj=6981

A systematic review of randomized controlled trials of the Wenyang Huoxue method in treating diabetic peripheral neuropathy.

Objective:To assess the efficacy and safety of the Wenyang Huoxue method for patients with diabetic peripheral neuropathy.Methods:A systematic literature search was performed using 7 databases: PUBMED, EMBASE, the Chinese National Knowledge Infrastructure, Wanfang, Chinese BioMedical, and the VIP Chinese Science and Technique Journals. The publication time was from the start of each database up to November 2018. Review Manager 5.3 software was used for assessing potential bias, data synthesis, and the subgroup analysis. Begg and Egger tests were used to assess funnel plot symmetries using Stata 14.0 software. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was used to assess the quality of evidence.Results:A total of 22 trials involving 1835 participants were eligible. There were significant differences in a total effective rate between the Wenyang Huoxue method combined with Western medicine and Western medicine alone (RR = 1.33, 95% CI 1.26–1.41; P < .00001). As for the sensory conduction velocity (SCV) of the peroneal nerve, the Wenyang Huoxue method combined with Western medicine compared with Western medicine alone had a significant increase (weighted mean difference [WMD] = 5.00, 95% CI 3.42–6.57; P < .00001). Also, the Wenyang Huoxue method combined with Western medicine had significant increases in motor conduction velocity (MCV) of the peroneal nerve (WMD = 4.48, 95% CI 3.78–5.19; P < .00001), tibial nerve SCV (WMD = 3.47, 95% CI 2.66–4.28; P < .00001), tibial nerve MCV (4.87, 95% CI 3.21–6.53; P < .00001), median nerve SCV (WMD = 3.78, 95% CI 3.07–4.50; P < .00001), and median nerve MCV (WMD = 4.50, 95% CI 3.40–5.59; P < .00001). However, the effect of the Wenyang Huoxue method on fasting blood glucose, 2-h postprandial blood glucose, and glycosylated hemoglobin was not statistically significant. Egger's test results showed that there was no publication bias (P = .0008), but the trim and filling method showed steady results. An influence analysis showed that no single study affected the overall result. The GRADE quality of the evidence was low to moderate across the different outcomes.Conclusion:Despite of the apparently positive findings, the quality of GRADE is not high, suggesting that the Wenyang Huoxue method can improve nerve conduction velocity to a certain extent, but more rigorous literature is needed to support this evidence.

Nanoparticle–microRNA-146a-5p polyplexes ameliorate diabetic peripheral neuropathy by modulating inflammation and apoptosis

Nontoxic and nonimmunogenic nanoparticles play an increasingly important role in the application of pharmaceutical nanocarriers. The pathogenesis of diabetic peripheral neuropathy (DPN) has been extensively studied. However, the role of microRNAs in DPN remains to be clarified. We verified in vitro that miR-146a-5p mimics inhibited the expression of proinflammatory cytokines and apoptosis. Then, we explored the protective effect of nanoparticle–miRNA-146a-5p polyplexes (nano-miR-146a-5p) on DPN rats. We demonstrated that nano-miR-146a-5p improved nerve conduction velocity and alleviated the morphological damage and demyelination of the sciatic nerve of DPN rats. The expression of the inflammatory cytokines, caspase-3, and cleaved caspase-3 in the sciatic nerve was inhibited by nano-miR-146a-5p. Additionally, nano-miR-146a-5p increased the expression of myelin basic protein. These results all indicated that nano-miR-146a-5p had a protective effect on peripheral nerves in the DPN rat model, which may occur through the regulation of the inflammatory response and apoptosis.

Zusanli (ST36) Acupoint Injection for Diabetic Peripheral Neuropathy: A Systematic Review of Randomized Controlled Trials.

Background: Acupuncture point (acupoint) injection is a common practice in China. Some trials showed that Chinese herbal extracts and/or conventional medication are injected at the Zusanli (ST36) acupoint for the treatment of diabetic peripheral neuropathy (DPN). The study aimed to assess the effectiveness and safety of acupoint injection for DPN at the ST36 by systematically evaluating the evidence published to date. Methods: Six databases were searched for randomized controlled trials (RCTs) of ST36 injection for DPN with primary outcome of pain, global symptom improvement, and quality of life. Methodological quality was assessed by the Cochrane risk of bias (ROB) tool. Data were analyzed using RevMan 5.3. Results: Fourteen RCTs involving 1,071 participants with DPN were included. All RCTs were assessed as unclear or high ROB. Few RCTs adequately reported methodology-related items and needling details according to Consolidated Standards of Reporting Trials (CONSORT) and Standards for Reporting Interventions in Controlled Trials of Acupuncture (STRICTA) statement. Medications injected at ST36 included conventional medications (11 RCTs) and Chinese herbal extracts (3 RCTs). The authors of this study did not perform any meta-analysis due to the heterogeneity of medications used for injections. Two individual RCTs favored ST36 injection in relieving pain compared with intramuscular injection of the same medication. For global symptom measured by Toronto clinical scoring system, one RCT showed that ST36 injection of Fufang Danggui was more effective than intramuscular injection of vitamin B12, two RCTs demonstrated that ST36 injection of mecobalamin or Danhong with cointervention was superior, while one RCT showed no significant differences between ST36 injection and intramuscular injection of mecobalamin. For improving nerve conduction velocity (NCV), three of four individual RCTs showed that ST36 injection was better than intramuscular or intravenous injection of the same medication, two RCTs favored ST36 injection with cointervention, and one RCT favored ST36 injection without cointervention. Four RCTs reported monitoring adverse events, all of which showed no significant difference between groups. Conclusions: Limited evidence suggests that ST36 injection appears to be safe, and potentially effective in reducing pain score and improving NCV compared with intramuscular injection of the same medication. However, poor methodological and reporting quality reduced confidence in the findings. Rigorously designed and well-reported RCTs evaluating the effectiveness of ST36 injection for DPN are warranted.