Diabetic peripheral neuropathy and neuromodulation techniques:a systematic review of progress and prospects

Neuromodulation for diabetic peripheral neuropathy represents a significant area of interest in the management of chronic pain associated with this condition.Diabetic peripheral neuropathy,a common complication of diabetes,is characterized by nerve damage due to high blood sugar levels that lead to symptoms,such as pain,tingling,and numbness,primarily in the hands and feet.The aim of this systematic review was to evaluate the efficacy of neuromodulatory techniques as potential therapeutic interventions for patients with diabetic peripheral neuropathy,while also examining recent developments in this domain.The investigation encompassed an array of neuromodulation methods,including frequency rhythmic electrical modulated systems,dorsal root ganglion stimulation,and spinal cord stimulation.This systematic review suggests that neuromodulatory techniques may be useful in the treatment of diabetic peripheral neuropathy.Understanding the advantages of these treatments will enable physicians and other healthcare providers to offer additional options for patients with symptoms refractory to standard pharmacologic treatments.Through these efforts,we may improve quality of life and increase functional capacity in patients suffering from complications related to diabetic neuropathy.

Cell metabolism pathways involved in the pathophysiological changes of diabetic peripheral neuropathy

Diabetic peripheral neuropathy is a common complication of diabetes mellitus.Elucidating the pathophysiological metabolic mechanism impels the generation of ideal therapies.However,existing limited treatments for diabetic peripheral neuropathy expose the urgent need for cell metabolism research.Given the lack of comprehensive understanding of energy metabolism changes and related signaling pathways in diabetic peripheral neuropathy,it is essential to explore energy changes and metabolic changes in diabetic peripheral neuropathy to develop suitable treatment methods.This review summarizes the pathophysiological mechanism of diabetic peripheral neuropathy from the perspective of cellular metabolism and the specific interventions for different metabolic pathways to develop effective treatment methods.Various metabolic mechanisms(e.g.,polyol,hexosamine,protein kinase C pathway)are associated with diabetic peripheral neuropathy,and researchers are looking for more effective treatments through these pathways.

Advances in the treatment of diabetic peripheral neuropathy by modulating gut microbiota with traditional Chinese medicine

Diabetic peripheral neuropathy(DPN)is one of the strongest risk factors for diabetic foot ulcers(neuropathic ulcerations)and the existing ulcers may further deteriorate due to the damage to sensory neurons.Moreover,the resulting numbness in the limbs causes difficulty in discovering these ulcerations in a short time.DPN is associated with gut microbiota dysbiosis.Traditional Chinese medicine(TCM)compounds such as Shenqi Dihuang Decoction,Huangkui Capsules and Qidi Tangshen Granules can reduce the clinical symptoms of diabetic nephropathy by modulating gut microbiota.The current review discusses whether TCM compounds can reduce the risk of DPN by improving gut microbiota.

Targeted metabolomics reveals the aberrant energy status in diabetic peripheral neuropathy and the neuroprotective mechanism of traditional Chinese medicine JinMaiTong

Diabetic peripheral neuropathy (DPN) is a common and devastating complication of diabetes, for which effective therapies are currently lacking. Disturbed energy status plays a crucial role in DPN pathogenesis. However, the integrated profile of energy metabolism, especially the central carbohydrate metabolism, remains unclear in DPN. Here, we developed a metabolomics approach by targeting 56 metabolites using high-performance ion chromatography-tandem mass spectrometry (HPIC-MS/MS) to illustrate the integrative characteristics of central carbohydrate metabolism in patients with DPN and streptozotocin-induced DPN rats. Furthermore, JinMaiTong (JMT), a traditional Chinese medicine (TCM) formula, was found to be effective for DPN, improving the peripheral neurological function and alleviating the neuropathology of DPN rats even after demyelination and axonal degeneration. JMT ameliorated DPN by regulating the aberrant energy balance and mitochondrial functions, including excessive glycolysis restoration, tricarboxylic acid cycle improvement, and increased adenosine triphosphate (ATP) generation. Bioenergetic profile was aberrant in cultured rat Schwann cells under high-glucose conditions, which was remarkably corrected by JMT treatment. In-vivo and in-vitro studies revealed that these effects of JMT were mainly attributed to the activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK) and downstream peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). Our results expand the therapeutic framework for DPN and suggest the integrative modulation of energy metabolism using TCMs, such as JMT, as an effective strategy for its treatment.

Non-pharmacological interventions for diabetic peripheral neuropathy:Are we winning the battle?

Despite the advent of relatively reliable modalities of diagnosing diabetic peripheral neuropathy(DPN),such as nerve conduction studies,there is still a knowledge gap about the pathophysiology,and thus limited available in-terventions for symptom control and curtailing disease progression.The pharma-cologic aspect of management is mainly centred on pain control,however,there are several important aspects of DPN such as loss of vibration sense,pressure sense,and proprioception which are associated with risks to lower limb health,which pharmacotherapy does not address.Furthermore,published evidence suggests non-pharmacologic interventions such as glycaemic control through dietary modification and exercise need to be combined with other measures such as psychotherapy,to reach a desired,however modest effect.Acupuncture is emerging as an important treatment modality for several chronic medical conditions including neuropathic and other pain syndromes.In their study published in the World Journal of Diabetes on the potential of acupuncture to reduce DPN symptoms and enhance nerve conduction parameters,Hoerder et al have been able to demonstrate that acupuncture improves sensory function and that this effect is likely sustained two months after treatment cessation.Although previous studies also support these findings,larger multi-center randomized control trials including a sham-controlled arm accounting for a placebo effect are required.Overall,given the satisfactory safety profile and the positive results found in these studies,it is likely that acupuncture may become an important aspect of the repertoire of effective DPN management.

Systematic investigation of Radix Salviae for treating diabetic peripheral neuropathy disease based on network Pharmacology

BACKGROUND Diabetic peripheral neuropathy(DPN)is a debilitating complication of diabetes mellitus with limited available treatment options.Radix Salviae,a traditional Chinese herb,has shown promise in treating DPN,but its therapeutic mech-anisms have not been systematically investigated.AIM Radix Salviae(Danshen in pinin),a traditional Chinese medicine(TCM),is widely used to treat DPN in China.However,the mechanism through which Radix Salviae treats DPN remains unclear.Therefore,we aimed to explore the mechanism of action of Radix Salviae against DPN using network pharmacology.METHODS The active ingredients and target genes of Radix Salviae were screened using the TCM pharmacology database and analysis platform.The genes associated with DPN were obtained from the Gene Cards and OMIM databases,a drug-com-position-target-disease network was constructed,and a protein–protein inter-action network was subsequently constructed to screen the main targets.Gene Ontology(GO)functional annotation and pathway enrichment analysis were performed via the Kyoto Encyclopedia of Genes and Genomes(KEGG)using Bioconductor.RESULTS A total of 56 effective components,108 targets and 4581 DPN-related target genes of Radix Salviae were screened.Intervention with Radix Salviae for DPN mainly involved 81 target genes.The top 30 major targets were selected for enrichment analysis of GO and KEGG pathways.CONCLUSION These results suggested that Radix Salviae could treat DPN by regulating the AGE-RAGE signaling pathway and the PI3K-Akt signaling pathway.Therefore,Danshen may affect DPN by regulating inflammation and apoptosis.

Clinical Efficacy of Pentoxifylline Combined with Thioctic Acid in the Treatment of Painful Diabetic Peripheral Neuropathy

Objective:To observe the efficacy of pentoxifylline+thioctic acid in the treatment of patients with painful diabetic peripheral neuropathy(PDPN).Methods:70 patients with PDPN admitted from October 2019 to October 2022 were selected and randomly grouped,with pentoxifylline+thioctic acid treatment in Group A and thioctic acid treatment in Group B,and the treatment efficacy was compared.Results:The treatment efficacy in Group A was higher than that of Group B,P<0.05;the points of each symptom of PDPN in Group A were lower than that of Group B,P<0.05;the C-reactive protein and electromyography indexes of PDPN patients in Group A were better than that of Group B,P<0.05.Conclusion:PDPN patients treated with pentoxifylline+thioctic acid can optimize nerve function,inhibit inflammation progression,and reduce PDPN symptoms,which is an efficient and feasible treatment option.

Validation of neuropathic pain assessment tools among Chinese patients with painful diabetic peripheral neuropathy

Objective:This study aims to evaluate the reliability and validity of neuropathic pain assessment tools among Chinese patients with painful diabetic peripheral neuropathy(PDPN).Methods:One hundred patients with PDPN and 70 patients with non-neuropathic pain were recruited from five grade III general hospitals in Guangzhou.Pain was assessed using the Leeds Assessment of Neuropathic Symptoms and Signs(LANSS),Douleur Neuropathique 4 questionnaire(DN4),and Brief Pain Inventory for Painful Diabetic Peripheral Neuropathy(BPI-DPN).Reliability was evaluated by internal consistency of the Cronbach's a coefficient and Guttman split-half.Construct validity was analyzed by factor analysis and Spearman correlation coefficients.Sensitivity and specificity were also assessed.Results:The Cronbach's a coefficients of the LANSS,DN4,and BPI-DPN were 0.735,0.750,and 0.898,respectively.The Guttman split-half coefficients of the LANSS,DN4,and BPIDPN were 0.660,0.726,and 0.849,respectively.The cumulative contributions of the LANSS,DN4,and BPI-DPN to the total variance were 61.945%,57.010%,and 66.056%,respectively.The items of the LANSS,DN4,and BPI-DPN presented high factorial loads,ranging from 0.387 to 0.841,0.137 to 0.948,and 0.487 to 0.953,respectively.The LANSS and DN4 exhibited sensitivities of 58.0%and 82.7%,respectively,and specificity of 97.1%.Conclusions:The LANSS or DN4 can be used to detect neuropathic pain in Chinese patients with PDPN.The BPI-DPN can be employed to monitor the effectiveness of pain intervention.

CLINICAL AND ELECTROPHYSIOLOGICAL OBSERVATIONS ON DIABETIC PERIPHERAL NEUROPATHYTREATED BY WARM NEEDLING AND MOXIBUSTION

Objective To observe clinical therapeutic effects of warm needling and moxibustion on diabetic peripheral neuropathy （DPN） and their influence on nerve conduction velocity. Methods Fifty two cases were randomly divided into a treatment group （n =26） and a control group （n =26）. In addition to basic treatment for lowering blood sugar in both groups, Pǐshū （BL 20）, Shènshū （BL 23）, Huántiào （GB 30）, Zùsānlǐ （ST 36）, Yánglíngquán （GB 34）, Sānyīnjiāo （SP 6）, Tàixī （KI 3）, Qǔchí （LI 11）, Wàiguān （TE 5） and Hégǔ （LI 4） were selected for warm needling and moxibustion in the treatment group. Methycobal was intramuscularly injected in the control group. Clinical symptoms and conduction velocities of the tibial nerve and common peroneal nerve were compared before and after treatment. Results Warm needling and moxibustion could alleviate such clinical symptoms as numbness of limbs, pain and hypoesthesia, and obviously improve the conduction velocities of both tibial and common peroneal nerves. Conclusion Warm needling and moxibustion exhibit good therapeutic effects on diabetic peripheral neuropathy.

Epalrestat protects against diabetic peripheral neuropathy by alleviating oxidative stress and inhibiting polyol pathway

Epalrestat is a noncompetitive and reversible aldose reductase inhibitor used for the treatment of diabetic neuropathy. This study assumed that epalrestat had a protective effect on diabetic peripheral nerve injury by suppressing the expression of aldose reductase in peripheral nerves of diabetes mellitus rats. The high-fat and high-carbohydrate model rats were established by intraperitoneal injection of streptozotocin. Peripheral neuropathy occurred in these rats after sustaining high blood glucose for 8 weeks. At 12 weeks after streptozotocin injection, rats were intragastrically administered epalrestat 100 mg/kg daily for 6 weeks. Transmission electron microscope revealed that the injuries to myelinated nerve fibers, non-myelinated nerve fibers and Schwann cells of rat sciatic nerves had reduced compared to rats without epalrestat administuation. Western blot assay and immunohistochemical results demonstrated that after intervention with epalrestat, the activities of antioxidant enzymes such as superoxide dismutase, catalase and glutathione peroxidase gradually increased, but aldose reductase protein expression gradually diminished. Results confirmed that epalrestat could protect against diabetic peripheral neuropathy by relieving oxidative stress and suppressing the polyol pathway.

Huangqi Guizhi Wuwu Decoction for treating diabetic peripheral neuropathy：a meta-analysis of 16 randomized controlled trials

OBJECTIVE：This meta-analysis was performed to systematically assess the efficacy and safety of the Chinese herbal medicine Huangqi Guizhi Wuwu Decoction（HGWWD） for treating diabetic peripheral neuropathy.DATA SOURCES：Six electronic databases,including the Cochrane Library,MEDLINE database,Chinese Biomedical Database,Chinese National Knowledge Infrastructure Database,Chinese Science and Technique Journals Database,and the Wanfang Database,were search ed on the internet for randomized controlled trials published up until 1 December 2015.The search terms included ＂Chinese herbal medicine＂,＂diabetic peripheral neuropathy＂ and ＂randomized controlled trials＂ in Chinese and in English.DATA SELECTION：We included randomized controlled trials using HGWWD/modified HGWWD for the treatment group,without restriction for the control group.We assessed literature quality in accordance with the Cochrane Review Handbook.A random or a fixed effects model was used to analyze outcomes using Rev Man 5.2 software.OUTCOME MEASURES：The primary outcomes were changes in symptoms and nerve conduction velocities.The secondary outcomeswere fasting blood glucose and hemorheological indexes.RESULTS：Sixteen randomized controlled trials,with a total of 1,173 patients,were included.Meta-analysis revealed that the efficacy of HGWWD for diabetic peripheral neuropathy was significantly superior compared with the control treatment（i.e.,control group）（risk ratio = 0.36,95% confidence interval（CI）：0.29–0.46,Z =8.33,P 〈 0.00001） Compared with the control group,there was an increase in median motor nerve conduction velocity（mean difference（MD） = 3.46,95%CI：1.88–5.04,Z = 4.30,P 〈 0.01） and median sensory nerve conduction velocity（MD = 3.30,95%CI：2.04–4.56,Z = 5.14,P 〈 0.01）.There was also an increase in peroneal motor nerve conduction velocity（MD = 3.22,95%CI：2.45–3.98,Z = 8.21,P 〈 0.01） and peroneal sensory nerve conduction velocity（MD = 3.05,95%CI：2.01–4.09,Z = 5.75,P 〈 0.01） in the treatment groups.No significant difference in fasting blood glucose was found between the treatment groups and the control groups（MD =-0.12,95%CI：-0.42–0.19,Z = 0.76,P = 0.45）.Plasma viscosity was significantly decreased after treatment（MD =-0.11,95%CI：-0.21 to-0.02,Z = 2.30,P = 0.02）.No significant difference in fibrinogen was detectable（MD =-0.53,95%CI：-1.28–0.22,Z = 1.38,P = 0.17）.Four trials reported that treatment groups experienced no adverse reactions.Adverse events were not mentioned in the other 12 trials.No trial reported the incidence of complications,quality of life outcomes,or health economics.CONCLUSION：HGWWD treatment improves diabetic neurologic symptoms and ameliorates nerve conduction velocities.Our study suggests that HGWWD may have significant therapeutic efficacy for the treatment of diabetic peripheral neuropathy.However,the methodological quality of the randomized controlled trials was generally low.Larger and better-designed randomized controlled trials are required to more reliably assess the clinical effectiveness of HGWWD.

Relationship between sonographically measured median nerve cross-sectional area and presence of peripheral neuropathy in diabetic subjects

BACKGROUND Neuropathy is a common complication of diabetes mellitus resulting from direct damage by hyperglycemia to the nerves and/or ischemia by microvascular injury to the endoneurial vessels which supply the nerves. Median nerve is one of the peripheral nerves commonly affected in diabetic neuropathy. The median nerve size has been studied in non-Nigerian diabetic populations. In attempt to contribute to existing literature, a study in a Nigerian population is needed.AIM To evaluate the cross-sectional area(CSA) of the median nerve using B-mode ultrasonography(USS) and the presence of peripheral neuropathy(PN) in a cohort of adult diabetic Nigerians.METHODS Demographic and anthropometric data of 85 adult diabetes mellitus(DM) and 85 age-and sex-matched apparently healthy control(HC) subjects were taken. A complete physical examination was performed on all study subjects to determine the presence of PN and modified Michigan Neuropathy Screening Instrument(MNSI) was used to grade its severity. Venous blood was taken from the study subjects for fasting lipid profile(FLP), fasting blood glucose(FBG) and glycated haemoglobin(HbA1 c) while their MN CSA was evaluated at a point 5 cm proximal to(5 cmCATL) and at the carpal tunnel(CATL) by high-resolution Bmode USS. Data was analysed using SPSS version 22.RESULTS The mean MN CSA was significantly thicker in DM subjects compared to the HC at 5 cmCATL(P < 0.01) and at the CATL(P < 0.01) on both sides. The presence of diabetic peripheral neuropathy(DPN) further increased the MN CSA at the CATL(P < 0.05) but not at 5 cmCATL(P > 0.05). However, the severity of DPN had no additional effect on MN CSA 5 cm proximal to and at the CATL. There was no significant association between MN CSA and duration of DM and glycemic control.CONCLUSION Thickening of the MN CSA at 5 cmCATL and CATL is seen in DM. Presence of DPN is associated with worse thickening of the MN CSA at the CATL but not at5 cmCATL. Severity of DPN, duration of DM, and glycemic control had no additional effect on the MN CSA.

Amplitude of sensory nerve action potential in early stage diabetic peripheral neuropathy:an analysis of 500 cases

Early diagnosis of diabetic peripheral neuropathy is important for the successful treatment of diabetes mellitus. In the present study, we recruited 500 diabetic patients from the Fourth Affiliated Hospital of Kunming Medical University in China from June 2008 to September 2013：221 cases showed symptoms of peripheral neuropathy （symptomatic group） and 279 cases had no symptoms of peripheral impairment （asymptomatic group）. One hundred healthy control subjects were also recruited. Nerve conduction studies revealed that distal motor latency was longer, sensory nerve conduction velocity was slower, and sensory nerve action potential and amplitude of compound muscle action potential were significantly lower in the median, ulnar, posterior tibial and common peroneal nerve in the diabetic groups compared with control subjects. Moreover, the alterations were more obvious in patients with symptoms of peripheral neuropathy. Of the 500 diabetic patients, neural conduction abnormalities were detected in 358 cases （71.6%）, among which impairment of the common peroneal nerve was most prominent. Sensory nerve abnormality was more obvious than motor nerve abnormality in the diabetic groups. The amplitude of sensory nerve action potential was the most sensitive measure of peripheral neuropathy. Our results reveal that varying degrees of nerve conduction changes are present in the early, asymptomatic stage of diabetic peripheral neuropathy.

Diabetic corneal neuropathy as a surrogate marker for diabetic peripheral neuropathy

Diabetic neuropathy is a prevalent microvascular complication of diabetes mellitus,affecting nerves in all parts of the body including corneal nerves and peripheral nervous system,leading to diabetic corneal neuropathy and diabetic peripheral neuropathy,respectively.Diabetic peripheral neuropathy is diagnosed in clinical practice using electrophysiological nerve conduction studies,clinical scoring,and skin biopsies.However,these diagnostic methods have limited sensitivity in detecting small-fiber disease,hence they do not accurately reflect the status of diabetic neuropathy.More recently,analysis of alterations in the corneal nerves has emerged as a promising surrogate marker for diabetic peripheral neuropathy.In this review,we will discuss the relationship between diabetic corneal neuropathy and diabetic peripheral neuropathy,elaborating on the foundational aspects of each:pathogenesis,clinical presentation,evaluation,and management.We will further discuss the relevance of diabetic corneal neuropathy in detecting the presence of diabetic peripheral neuropathy,particularly early diabetic peripheral neuropathy;the correlation between the severity of diabetic corneal neuropathy and that of diabetic peripheral neuropathy;and the role of diabetic corneal neuropathy in the stratification of complications of diabetic peripheral neuropathy.

Prostaglandin E_1 in conjunction with high doses of vitamin B_(12) improves nerve conduction velocity of patients with diabetic peripheral neuropathy

BACKGROUND： Prostaglandin El improves diabetic peripheral neuropathy in symptoms and sensory threshold. Vitamin Bi and methyl-vitamin BI2 improve microcirculation to peripheral nerve tissue and promote neurotrophy. OBJECTIVE： To observe motor nerve and sensory nerve conduction velocity in patients with diabetic peripheral neuropathy, prior to and after treatment with prostaglandin El, vitamin B I and different doses of vitamin B 12. DESIGN, TIME AND SETTING： Randomized, controlled experiment, performed at the Department of Neurology, Beijing Hantian Central Hospital, between February 2002 and September 2007. PARTICIPANTS： A total of 122 patients with type 2 diabetic peripheral neuropathy; 73 males and 49 females were included. All patients met the diagnostic criteria of diabetes mellitus, as determined by the World Health Organization in 1999 and 2006, and also the diagnostic criteria of diabetic peripheral neuropathy. For each subject, conduction disorders in the median nerve and in the common peroneal nerve were observed using electromyogram. Also, after diet and drug treatment, the blood glucose level of subjects was observed to be at a satisfactory level for more than two weeks, and the symptoms of diabetic peripheral neuropathy were not alleviated. METHODS： All patients were randomly divided into the following three groups. A control group （n = 40）, in which, 100 mg vitamin B1 and 500 μg vitamin BI2 were intramuscularly injected. A vitamin B12 low-dose treated group （ n = 42）, in which 10 μ g prostaglandin E1 in 250 mL physiological saline was intravenously injected once a day and 100 mg vitamin BI and 500 11 g vitamin BI2 was intramuscularly injected once a day. Lastly, a vitamin B12 high-dose treated group （n = 40）, in which administration was the same as in the vitamin B12 low-dose treated group, except that 500 11 g vitamin BI2 was replaced by 1mg vitamin B12. Administration was performed for four weeks for each group. MAIN OUTCOME MEASURES： The motor nerve and sensory nerve conduction velocity of the median nerve and the common peroneal nerve were determined using an electromyogram electronic stimulator （Neuropack-11, Nihon Kohden, Japan）. RESULTS： The motor nerve and sensory nerve conduction velocities of the median nerve and the common peroneal nerve were significantly faster after treatment compared to before treatment in all 3 groups （P 〈 0.05q）.01）. Compared with the control group, the motor nerve and sensory nerve conduction velocities were significantly faster in the vitamin B12 low-dose treated group and in the vitamin B12 high-dose treated group （P 〈 0.01）. The motor nerve and sensory nerve conduction velocities were significantly faster in the vitamin B12 high-dose treated group compared to the vitamin B12 low-dose treated group （P 〈 0.05）. CONCLUSION： Prostaglandin E1, in conjunction with vitamin B12, can improve neural functional states and speed up peripheral motor nerve and sensory nerve conduction velocity in diabetic peripheral neuropathy. In addition, better effects are achieved using prostaglandin E1 in conjunction with high doses of vitamin B 12.

The circ_0002538/miR-138-5p/plasmolipin axis regulates Schwann cell migration and myelination in diabetic peripheral neuropathy

Circular RNAs(circRNAs)play a vital role in diabetic peripheral neuropathy.However,their expression and function in Schwann cells in individuals with diabetic peripheral neuropathy remain poorly understood.Here,we performed protein profiling and circRNA sequencing of sural nerves in patients with diabetic peripheral neuropathy and controls.Protein profiling revealed 265 differentially expressed proteins in the diabetic peripheral neuropathy group.Gene Ontology indicated that differentially expressed proteins were mainly enriched in myelination and mitochondrial oxidative phosphorylation.A real-time polymerase chain reaction assay performed to validate the circRNA sequencing results yielded 11 differentially expressed circRNAs.circ_0002538 was markedly downregulated in patients with diabetic peripheral neuropathy.Further in vitro experiments showed that overexpression of circ_0002538 promoted the migration of Schwann cells by upregulating plasmolipin(PLLP)expression.Moreover,overexpression of circ_0002538 in the sciatic nerve in a streptozotocin-induced mouse model of diabetic peripheral neuropathy alleviated demyelination and improved sciatic nerve function.The results of a mechanistic experiment showed that circ_0002538 promotes PLLP expression by sponging miR-138-5p,while a lack of circ_0002538 led to a PLLP deficiency that further suppressed Schwann cell migration.These findings suggest that the circ_0002538/miR-138-5p/PLLP axis can promote the migration of Schwann cells in diabetic peripheral neuropathy patients,improving myelin sheath structure and nerve function.Thus,this axis is a potential target for therapeutic treatment of diabetic peripheral neuropathy.

Cerebrolysin improves sciatic nerve dysfunction in a mouse model of diabetic peripheral neuropathy

To examine the effects of Cerebrolysin on the treatment of diabetic peripheral neuropathy, we first established a mouse model of type 2 diabetes mellitus by administering a high-glucose, high-fat diet and a single intraperitoneal injection of streptozotocin. Mice defined as diabetic in this model were then treated with 1.80, 5.39 or 8.98 m L/kg of Cerebrolysin via intraperitoneal injections for 10 consecutive days. Our results demonstrated that the number, diameter and area of myelinated nerve fibers increased in the sciatic nerves of these mice after administration of Cerebrolysin. The results of several behavioral tests showed that Cerebrolysin dose-dependently increased the slope angle in the inclined plane test（indicating an improved ability to maintain body position）, prolonged tail-flick latency and foot-licking time（indicating enhanced sensitivity to thermal and chemical pain, respectively, and reduced pain thresholds）, and increased an index of sciatic nerve function in diabetic mice compared with those behavioral results in untreated diabetic mice. Taken together, the anatomical and functional results suggest that Cerebrolysin ameliorated peripheral neuropathy in a mouse model of type 2 diabetes mellitus.

Microsurgical decompression of the median nerves for treating diabetic peripheral neuropathy in the upper limbs: A 21-month follow-up

BACKGROUND： Peripheral nerve injured by abnormal glucose metabolism is compressed, which is an important etiological factor of diabetic peripheral neuropathy （DPN）. Microsurgical decompression of peripheral nerve maybe effectively releases the symptoms of DPN. OBJECTIVE： To investigate the curative effects of microsurgical decompression of median nerves for treatment of DPN in upper limbs. DESIGN： Case-follow up observation. SETTING： Department of Orthopaedics, Department of Neurosurgery, China-Japan Friendship Hospital, Ministry of Health. PARTICIPANTS： Twelve patients with DPN in upper limbs （19 hands） who received treatment in the Department of Orthopaedics, Department of Neurosurgery, China-Japan Friendship Hospital, Ministry of Public Health between March 2004 and July 2006 were involved in this experiment. The involved patients, 5 male and 7 female, were aged 44 to 77 years, with DPN course of 6 months to 16 years. They all met 1999 WHO diabetic diagnosis criteria. Both two hands had symptom in 7 patients, and only one hand had symptom in 5 patients. Informed consents of detected items were obtained from all the patients, who also received 21 months of follow-up treatment. METHODS： （1）Operation was carried out under the anesthetic status of brachial plexus. Under an operating microscope, transverse carpal ligament was exposed. Subsequently, transverse carpal ligament, forearm superficial fascia and palmar aponeurosis were fully liberated, and then part of them was cut off. Connective tissue around median nerve, superficial flexor muscle of fingers, radial flexor, palmaris longus and other flexor tendons were completely loosened. Finally, epineurium was opened with microinstrument for neurolysis. After tourniquet was loosened, and bipolar coagulator was used to stop bleeding, and the incision was closed. （2） In postoperative 21 months, the subjective symptom, two-point discrimination （The smallest distance of two normal points was 3 to 6 mm）, nerve conduction velocity and action potential amplitude （short abductor muscle of thumb end Lat 〈 4.5 ms; Motor nerve conduction velocity of forearm 〉 50 m/s）, etc. of all the patients were followed up. MAIN OUTCOME MEASURES＂ The objective evaluation and long-term follow up of curative effect of microsurgical decompression of median nerves for treatment of DPN in upper limbs. RESULTS： Twelve patients with DPN in upper limbs participated in the final analysis. （1） After operation, numbness and pain symptom releasing 100% were found in 19 hands of 12 patients with DPN. During follow up, numbness and recrudescent pain symptom were found in one hand （5%, 1/19）. （2）Postoperatively, index finger two point discrimination in 15 （94%, 15/16） hands recovered to normal. （3） nerve conduction velocity and action potential amplitude improved completely. （4） Two hands （2/19, 10% ）had poor healing at incision, and they late healed at postoperative 1 and 1.5 months, respectively. CONCLUSION： Long-term follow-up results show that microsurgical decompression is an effective method to treat DPN in upper limbs.

Balance training in the intervention of fall risk in elderly with diabetic peripheral neuropathy: A review

Diabetic peripheral neuropathy(DPN)was the most common complications of elderly diabetic,which could contribute to an increased risk of falling.Despite the increased prevalence of elderly diabetic,high risk of falls and serious consequences of falls in elderly with DPN,It is necessary to adopt means of reducing the risk of falls in elderly with DPN.Impaired balance in the elderly with DPN was the most important risk factor of increasing falls.This review will introduce the epidemiology of falls in elderly with DPN,analysis the reasons for high risk of falls in elderly with DPN,provide a review of the development of balance training in the intervention of fall risk in elderly with DPN and offer recommendations to medical personnels on how to provide an efficient balance training for elderly with DPN.

THE ROLE OF IGF-1 GENE EXPRESSION ABNORMALITY IN PATHOGENESIS OF DIABETIC PERIPHERAL NEUROPATHY

Objective. To explore the role of insulin-like growth factor 1 (IGF-1)gene expression abnormality in neurotrophic causes of diabetic peripheral neurophathy.Methods. Diabetes was induced in Sprague Dawley rats by alloxan. The parameters were measured as follows: IGF-1 mRNA by reverse transcriptase-polymerase chain reaction (RT-PCR); IGF-1 peptide by enzyme-linked immunosorbent assay (ELISA); electrophysiological parameters of nerves by evoked electromyogram; morphometric evaluation of sciatic nerves under light microscope and transmission electron microscope.Results. During early diabetic stage, IGF-1 mRNA [(0.430±0.031)vs. (0.370±0.016), P ＜0.01,(0.430 ± 0.031 ) vs. (0.280 ± 0.010) , P ＜0.001, respectively], IGF - 1 peptide contents [ (38.44 ± 3.60)ng/mgvs. (30.06±2.41) ng/mg, P ＜0.01, (38.44±3.6) ng/mgvs. (3.71 +2.70) ng/mg, P ＜0.001,respectively] in sciatic nerve tissue reduced in diabetic rats with hyperglycemia and varied with severity of diabetic state when compared with non-diabetic control rats, and further gradually down-regulated in the diabetic rats with duration of diabetes [IGF-1 mRNA (0. 320 ± 0. 021) ～ (0. 230 + 0. 060); IGF-1 peptide (28.80 ± 3.30) ～(19. 51 + 1.80)ng/mg]. Furthermore, they correlated with nerve functional (sensory nerve conduction velocity:r = 0. 741, P ＜0. 001; amplitude ofevokedpotential: r = 0. 716, P ＜0. 001, respectively)andstructuralabnormality (axonal areas r = 0. 81, P ＜ 0. 001 ) of sciatic nerve. No difference was found in the above parameters between diabetic rats with euglycemia and non-diabetic control group.Conclusion. IGF-1 gene expression in tissues was down-regulated from early diabetic stage, and varied with the severity and duration of diabetic state. The decrement in IGF-1 level might contribute to the initiation and development of diabetic neuropathy via autocrine or paracrine pathway.