Painful Diabetic Neuropathy Research Articles

What is the best pharmacologic treatment for painful diabetic peripheral neuropathy?

What is the best pharmacologic treatment for painful diabetic peripheral neuropathy?

Healthcare costs and medical utilization patterns associated with painful and severe painful diabetic peripheral neuropathy.

Painful diabetic peripheral neuropathy (DPN) is a common complication in patients with diabetes. It is associated with a poor quality of life and high costs of care. This study investigated the impact of painful DPN on healthcare costs and resource utilization. This was a retrospective analysis of administrative claims of adult patients with diabetes (type 1 or 2) from Optum's de-identified Clinformatics® Data Mart Database. Patients were assigned to four cohorts by presence of DPN and pain severity, based on diagnoses and prescription patterns in a one-year baseline. All-cause and diabetes-associated costs were calculated for the year following the index DPN diagnosis. Risk factors associated with presence of severely painful DPN were evaluated. Relative to those without DPN, patients who had DPN without pain, painful DPN (PDPN), or severe PDPN incurred respective increases of $3,093, $9,349, and $20,887 in average annual all-cause costs. More than half of costs from painful/severe DPN were for prescriptions and inpatient hospitalization. Severe PDPN was associated with elevated odds of diabetic amyotrophy (OR: 8.09; 95% CI: 6.84-9.56), diabetic foot ulcers (OR: 6.54, 95% CI: 6.32-6.76), and loss of mobility (OR: 2.54, 95% CI: 2.48-2.60), among other complications. Painful DPN is associated with higher healthcare costs and resource utilization, and a greater risk of debilitating conditions that limit quality of life. Future research should focus on better treatment options and more aggressive pain management strategies to reduce the negative impacts of DPN.

Metabolomic and lipidomic profiling of the spinal cord in type 2 diabetes mellitus rats with painful neuropathy

In this paper we investigated lipid and metabolite changes in diabetic neuropathy, using untargeted lipidomics and metabolomics analyses of the spinal cords from streptozotocin-treated diabetic rats.170 metabolites and 45 lipids were dysregulated in the painful diabetic neuropathy (PDN) phase. Pathway enrichment analysis revealed perturbations in starch and sucrose, tryptophan, pyrimidine, cysteine and methionine, thiamine, tyrosine, and nucleotides. The disturbance of tyrosine, tryptophan, methionine, triacylglycerol, and phosphatidylethanolamine metabolism indicated that pathological mechanisms in the PDN involved energy metabolism, oxidative stress, and neural reparative regeneration. These revelations offered potential biomarkers for PDN and enriched the comprehension of the complex molecular mechanisms characterizing PDN, establishing a solid foundation for subsequent inquiries into neural convalescence and recovery after PDN.

A New Application for Cenicriviroc, a Dual CCR2/CCR5 Antagonist, in the Treatment of Painful Diabetic Neuropathy in a Mouse Model.

The ligands of chemokine receptors 2 and 5 (CCR2 and CCR5, respectively) are associated with the pathomechanism of neuropathic pain development, but their role in painful diabetic neuropathy remains unclear. Therefore, the aim of our study was to examine the function of these factors in the hypersensitivity accompanying diabetes. Additionally, we analyzed the analgesic effect of cenicriviroc (CVC), a dual CCR2/CCR5 antagonist, and its influence on the effectiveness of morphine. An increasing number of experimental studies have shown that targeting more than one molecular target is advantageous compared with the coadministration of individual pharmacophores in terms of their analgesic effect. The advantage of using bifunctional compounds is that they gain simultaneous access to two receptors at the same dose, positively affecting their pharmacokinetics and pharmacodynamics and consequently leading to improved analgesia. Experiments were performed on male and female Swiss albino mice with a streptozotocin (STZ, 200 mg/kg, i.p.) model of diabetic neuropathy. We found that the blood glucose level increased, and the mechanical and thermal hypersensitivity developed on the 7th day after STZ administration. In male mice, we observed increased mRNA levels of Ccl2, Ccl5, and Ccl7, while in female mice, we observed additional increases in Ccl8 and Ccl12 levels. We have demonstrated for the first time that a single administration of cenicriviroc relieves pain to a similar extent in male and female mice. Moreover, repeated coadministration of cenicriviroc with morphine delays the development of opioid tolerance, while the best and longest-lasting analgesic effect is achieved by repeated administration of cenicriviroc alone, which reduces pain hypersensitivity in STZ-exposed mice, and unlike morphine, no tolerance to the analgesic effects of CVC is observed until Day 15 of treatment. Based on these results, we suggest that targeting CCR2 and CCR5 with CVC is a potent therapeutic option for novel pain treatments in diabetic neuropathy patients.

Genetically predicted immune cells mediate the association between gut microbiota and neuropathy pain

BackgroundPrevious observational studies have indicated a complex association between gut microbiota (GM) and neuropathic pain (NP). Nonetheless, the precise biological mechanisms underlying this association remain unclear. Therefore, we adopted a Mendelian randomization (MR) approach to investigate the causal relationship between GM and neuropathic pain including post-herpetic neuralgia (PHN), painful diabetic peripheral neuropathy (PDPN), and trigeminal neuralgia (TN), as well as to explore the potential mediation effects of immune cells.MethodsWe performed a two-step, two-sample Mendelian randomization study with an inverse variance-weighted (IVW) approach to investigate the causal role of GM on three major kinds of NP and the mediation effect of immune cells between the association of GM and NP. In addition, we determine the strongest causal associations using Bayesian weighted Mendelian randomization (BWMR) analysis. Furthermore, we will investigate the mediating role of immune cells through a two-step Mendelian randomization design.ResultsWe identified 53 taxonomies and pathways of gut microbiota that had significant causal associations with NP. In addition, we also discovered 120 immune cells that exhibited significant causal associations with NP. According to the BWMR and two-step Mendelian randomization analysis, we identified the following results CD4 on CM CD4 + (maturation stages of T cell) mediated 6.7% of the risk reduction for PHN through the pathway of fucose degradation (FUCCAT.PWY). CD28 + DN (CD4-CD8-) AC (Treg) mediated 12.5% of the risk reduction for PHN through the influence on Roseburia inulinivorans. CD45 on lymphocyte (Myeloid cell) mediated 11.9% of the risk increase for TN through the superpathway of acetyl-CoA biosynthesis (PWY.5173). HLA DR + CD8br %T cell (TBNK) mediated 3.2% of the risk reduction for TN through the superpathway of GDP-mannose-derived O-antigen building blocks biosynthesis (PWY.7323). IgD-CD38-AC (B cell) mediated 7.5% of the risk reduction for DPN through the pathway of thiazole biosynthesis I in E. coli (PWY.6892).DiscussionThese findings provided evidence supporting the causal effect of GM with NP, with immune cells playing a mediating role. These findings may inform prevention strategies and interventions directed toward NP. Future studies should explore other plausible biological mechanisms.

Study of a painful diabetic peripheral neuropathy model induced by streptozotocin: conclusions before investigating non-paralytic botulinum molecules

Painful diabetic peripheral neuropathy (PDPN) is a common complication of diabetes characterized by peripheral nerve dysfunction and debilitating pain symptoms. This article investigates the streptozotocin (STZ)-induced model of PDPN (45 mg/kg i.p.) to evaluate whether it can be further used to study the efficacy of non-paralytic botulinum molecules in pain control. In the study changes in relative weight, glucose levels, and mechanical and temperature sensitivity in the experimental group compared to the control group of rats were assessed. The obtained data indicate the reliability of the model. The results showed a significant decrease in relative weight and alterations in glucose levels in the experimental group, highlighting the metabolic impact of PDPN. Moreover, the rats in the experimental group exhibited heightened mechanical and temperature sensitivity, mirroring the neuropathic pain experienced by patients with PDPN. These findings support the suitability of the STZ-induced PDPN model for preclinical studies investigating non-paralytic botulinum molecules as analgesics. In conclusion, this model provides a valuable platform for future research aimed at understanding the underlying mechanisms and developing effective interventions for PDPN.

Efficacy and Safety of Trazodone and Gabapentin Fixed-Dose Combination in Patients Affected by Painful Diabetic Neuropathy: Randomized, Controlled, Dose-Finding Study.

Up to 50% of diabetic patients with neuropathy suffer from chronic pain, namely painful diabetic neuropathy (PDN), an unmet medical need with significant impact on quality of life. Gabapentin is widely used for PDN, albeit with frequent dose-limiting effects. Trazodone, an antidepressant with multi-modal action, has shown promising results when given at low doses as an add-on to gabapentin. Upon previous clinical trials and experimental evidence, a fixed-dose combination (FDC) of both compounds, at low doses, was developed for neuropathic pain. This was a phase II, randomized, double-blind, placebo and reference controlled, dose-finding, multicenter, international, prospective study. Male and female diabetic patients aged 18-75years and affected by PDN were eligible for enrolment. Patients were randomized (1:1:1:1:2 ratio) to trazodone and gabapentin (Trazo/Gaba) 2.5/25mg t.i.d. for 8weeks, Trazo/Gaba 5/50mg t.i.d. for 8weeks, Trazo/Gaba 10/100mg t.i.d. for 8weeks, gabapentin (Gaba), or placebo (PLB). The aim of the study was to collect preliminary information on the effect of the 3 different FDCs of Trazo/Gaba on pain intensity based on the 11-point numeric rating score (NRS) after 8weeks of treatment. The secondary objectives were the evaluation of the percentage of responders, neuropathic pain symptoms, anxiety, sleep, quality of life, safety, and tolerability. The primary efficacy endpoint was evaluated with last observation carried out forward (LOCF), using an analysis of covariance (ANCOVA), including treatment and centers as factors and baseline as covariate and applying linear contrast test, excluding the active treatment. Only if the linear contrast test was significant (p < 0.05), the step-down Dunnett test would be used to determine the minimum effective dose significantly different from PLB. If linearity was not verified, an adjusted ANCOVA model and comparisons with Dunnett test were performed. Before the application of the ANCOVA model, the non-significance of interaction treatment per baseline was verified. A total of 240 patients were included in the modified intention-to-treat (m-ITT) population: 39 in Trazo/Gaba 2.5/25mg, 38 in Trazo/Gaba 5/50mg, 37 in Trazo/Gaba 10/100mg, 83 in PLB, and 43 in Gaba. After 8weeks of treatment, changes of the average daily pain score based on the 11-point NRS from baseline were - 2.52 ± 2.31 in Trazo/Gaba 2.5/25mg group, - 2.24 ± 1.96 in Trazo/Gaba 5/50mg group, - 2.46 ± 2.12 in Trazo/Gaba 10/100mg group, - 1.92 ± 2.21 in Gaba group, and - 2.02 ± 1.95 in the PLB group. The linear contrast test did not result in significant differences (p > 0.05) among treatment groups. Consequently, the minimum effective dose against PLB was not determined. The multiple comparison with Dunnett adjustment did not show any statistically significant differences vs. PLB after 8weeks of treatment: Trazo/Gaba 2.5/25mg (95% confidence interval (CI) - 1.2739, 0.2026; p = 0.1539); Trazo/Gaba 5/50mg (95% CI - 0.9401, 0.5390; p = 0.5931); Trazo/Gaba 10/100mg (95% CI - 1.0342, 0.4582; p = 0.4471). However, patients receiving the lowest dose of Trazo/Gaba 2.5/25mg showed a statistically significant difference to PLB after 6weeks of treatment (95% CI - 1.6648, - 0.2126; p = 0.0116). Positive results were also found for responder patients, other items related to the pain, anxiety, depression, sleep, and quality of life, consistently in favor to the lowest Trazo/Gaba FDC. Two serious adverse events (SAEs) occurred but were judged unrelated to the study treatment. Treatment-emergent adverse events (TEAEs) were mainly mild-to-moderate in intensity and involved primarily nervous system, gastrointestinal disorders, and investigations. The primary end point of the study was the change from baseline of the average daily pain score based on the 11-point NRS after 8weeks of treatment. While the primary endpoint was not reached, patients treated with Trazo/Gaba 2.5/25mg t.i.d. showed statistically significant improvement of pain and other scores after 6weeks and reported consistent better results in comparison to PLB on primary and secondary endpoints for the overall study duration. According to these results, the lowest dose of Trazo/Gaba FDC may be the best candidate for further clinical development to confirm the potential benefits of the FDC drug for this condition. NCT03749642.

Amitriptyline, Pregabalin and Duloxetine for Treatment of Painful Diabetic Peripheral Neuropathy.

Painful diabetic peripheral neuropathy is one of the frequent presenting complaints in diabetes and endocrine clinics. Our main objective was to compare effectiveness of three commonly prescribed drugs: amitriptyline, pregabalin and duloxetine for treatment of painful diabetic peripheral neuropathy. This was a comparative, prospective, observational study conducted among 99 diabetic patients with painful diabetic peripheral neuropathy having numeric rating pain scale ≥ 4. Thirty-three patients in each group were consecutively prescribed amitriptyline, pregabalin and duloxetine in lower dose (10mg/75mg/20mg) for first two weeks to gradually up titrate to higher dose (25mg/150mg/30mg) as per pain response for total duration of eight weeks. At the end of eight weeks, 84.9% in amitriptyline, 78.7% in pregabalin and 60.6% in duloxetine group had adequate pain reduction in form of mild or no pain. Among total patients, 42.5% patients had severe pain at baseline that decreased to 5% by the end of our study. Out of three drugs, 45.5% patients in amitriptyline group had complete resolution of pain as compared to 24.2% in pregabalin and 18.2% in duloxetine group (p value 0.05). Drowsiness (42.4%), dizziness (21.2%) and dry mouth (21.2%) were the commonest side effects among total participants in our study. Amitriptyline, pregabalin and duloxetine were all associated with adequate pain reduction among patients of painful diabetic peripheral neuropathy in our study, however, amitriptyline had more favorable findings with tolerable side effects.

Increased Thalamocortical Functional Connectivity on Discontinuation of Treatment in Painful Diabetic Peripheral Neuropathy.

Altered functional connectivity has been demonstrated in key brain regions involved in pain processing in painful diabetic peripheral neuropathy (Painful-DPN). However, the impact of neuropathic pain treatment on functional connectivity has not been investigated. Sixteen participants underwent resting state functional MRI (rs-fMRI) when optimally treated for neuropathic pain during their involvement in the OPTION-DM trial and 1-week following withdrawal of treatment. On discontinuation of pain treatment, there was a rise in functional connectivity between the left thalamus and primary somatosensory cortex (S1) and the left thalamus and insular cortex, key brain regions that are involved in cerebral processing of pain. The changes in functional connectivity between scans also correlated with measures of pain (baseline pain severity and neuropathy pain symptom inventory). Moreover, when participants were stratified into higher and lower than average baseline pain sub-groups, the change in thalamic-S1 cortical functional connectivity between scans was significantly greater in those with high baseline pain compared with the lower baseline pain group. This study shows that thalamo-cortical functional connectivity has the potential to act as an objective biomarker for neuropathic pain in diabetes for use in clinical pain trials.

1892-LB: Impact of Ongoing Treatment with High Concentration Capsaicin Topical System on Affective Distress and Quality of Life in Patients with Painful Diabetic Neuropathy—A Retrospective Cohort Study

1892-LB: Impact of Ongoing Treatment with High Concentration Capsaicin Topical System on Affective Distress and Quality of Life in Patients with Painful Diabetic Neuropathy—A Retrospective Cohort Study

854-P: Global, Multicenter Registry of Prospectively-Enrolled Patients Utilizing SCS for Chronic Pain—Long-Term Outcomes from a Subcohort Diagnosed with Painful Diabetic Peripheral Neuropathy

854-P: Global, Multicenter Registry of Prospectively-Enrolled Patients Utilizing SCS for Chronic Pain—Long-Term Outcomes from a Subcohort Diagnosed with Painful Diabetic Peripheral Neuropathy

Efficacy and safety of acupuncture for painful diabetic neuropathy: a systematic review and meta-analysis.

Painful diabetic neuropathy (PDN) is a common chronic neurological complication of diabetes mellitus. Medications are often used to relieve pain, but with significant side effects. Acupuncture is now a component of pragmatic and integrative treatment for PDN. An increasing number of relevant randomized controlled trials have been published in recent years, but a comprehensive meta-analysis has not yet been performed. The aim of this paper is to verify the effectiveness and safety of acupuncture for PDN by meta-analysis and trial sequential analysis (TSA). All participants in this study should have had a PDN diagnosis and the trial group was treated with acupuncture. Eight databases, including EMbase, PubMed, Web of science, Cochrane Library, China Biology Medicine disc (CBM), China National Knowledge Infrastructure (CNKI), Wanfang and Chongqing VIP (CQVIP) were retrieved from inception to 5 April 2023. Meta-analysis was conducted utilizing RevMan 5.3 and Stata 15.0. TSA was performed to assess the adequacy of sample size for the outcomes. A total of 36 studies, comprising 2,739 PDN patients, were included. Among them, 1,393 patients were assigned to the trial group and 1,346 patients were treated in the control group. Outcomes covers the primary indicator Total effective rate (RR = 1.42, 95%CI [1.34, 1.52], p < 0.00001), with 21 studies reported, Pain intensity (SMD = -1.27, 95%CI [-1.58, -0.95], p < 0.00001), with 23 studies reported, and other outcomes, including motor nerve conduction velocity (MCV; MD = 3.58, 95%CI [2.77, 4.38], p < 0.00001), sensory nerve conduction velocity (SCV; MD = 3.62, 95%CI [2.75, 4.49], p < 0.00001), Depression score (SMD = -1.02, 95%CI [1.58, 0.46]), Toronto clinical scoring system (TCSS; MD = -2.41, 95%CI [-3.37, -1.45], p < 0.00001), Quality of life (SMD = 1.06, 95%CI [0.66, 1.46]), traditional Chinese medicine (TCM) syndrome score (MD = -4.99, 95%CI [-6.79, -3.18], p < 0.00001), suggesting that acupuncture have an ameliorating effect on PDN in various respect. Egger's test revealed publication bias for four outcomes. TSA showed that as for Total effective rate, Pain Intensity, MCV and SCV, the number of included studies was sufficient to support the conclusions. Acupuncture demonstrates significant effectiveness in improving PDN outcomes, including Total effective rate, Pain intensity, MCV, SCV, Depression score, TCSS, Quality of life, TCM syndrome score. But the Adverse events rate is no different in trail group and control group. The publication bias presented in Total effective rate, Pain intensity, MCV and SCV can be remedied by Trim and filling method. Prospero, https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=477295.

Assessment for Diabetic Neuropathy: Treatment and Neurobiological Perspective.

Diabetic neuropathy, also known as diabetic peripheral sensorimotor neuropathy (DPN), is a consequential complexity of diabetes, alongside diabetic nephropathy, diabetic cardiomyopathy, and diabetic retinopathy. It is characterized by signs and symptoms of peripheral nerve damage in diabetes patients after ruling out other causes. Approximately 20% of people with diabetes are affected by this painful and severe condition. The development of diabetic neuropathy is influenced by factors such as impaired blood flow to the peripheral nerves and metabolic issues, including increased polyol pathway activation, myo-inositol loss, and nonenzymatic glycation. The present review article provides a brief overview of the pathological changes in diabetic neuropathy and the mechanisms and types of DPN. Various diagnostic tests and biomarkers are available to assess nerve damage and its severity. Pharmacotherapy for neuropathic pain in diabetic neuropathy is complex. This review will explore current treatment options and potential future developments to improve the quality of life for patients suffering from diabetic neuropathy.

β-hydroxybutyrate alleviates neurological deficits by restoring glymphatic and inflammation after subarachnoid hemorrhage in mice

BackgroundBoth glymphatic system dysfunction and inflammatory response aggravate neurological dysfunction after subarachnoid hemorrhage (SAH). Studies have shown that β-hydroxybutyrate (BHB) may mitigate painful diabetic neuropathy (PDN) by upregulating SNTA1 expression and reinstating AQP4 polarity. However, the potential of BHB to ameliorate glymphatic system function and inflammatory response in SAH mice remains uncertain. MethodsThe SAH models were constructed by injection of arterial blood into cisterna Magana. Three groups of C57 mice were randomly assigned: Sham, SAH, and BHB. All mice were subjected to neurological function assessment, western blot, immunofluorescence double staining, and RNA-seq. Glymphatic system function was examined with tracer and immunofluorescence double staining, and the differential genes were examined with RNA-seq. In addition, the expression of related inflammation was detected. ResultsCompared with the SAH group, BHB reinstated AQP4 polarization by upregulating SNTA1 protein to enhance the glymphatic system. According to RNA-seq, the different genes were primarily connected to microglia activation, astrocytes, and inflammation. Western blot and immunofluorescence further confirmed that the related inflammatory protein expression levels were upregulated. BHB attenuated neuroinflammation after SAH. Ultimately, it can mitigate the neurological deficits in SAH mice. ConclusionThe study reveals a novel mechanism that BHB treatment mitigates neurologic impairment in SAH mice. We propose that BHB may play a neuroprotective effect by enhancing glymphatic system function and attenuating neuroinflammatory subarachnoid hemorrhage.

Use of gabapentin for neuropathic pain therapy: A view from perspective of evidence-based medicine

The aim of the study was to analyze the literature sources for pharmacodynamic and pharmacokinetic features of gabapentin, providing its use in patients with neuropathic pain, as well as a comparative evaluation of its efficacy and safety when used in different doses.Materials and methods. PubMed, Google Scholar, EMBASE, ResearchGate scientific information network and elibrary.ru databases were used as search resources. The keywords used for the search were “gabapentin”, “mechanism of action”, “gabapentin targets”, “gabapentin pharmacodynamics”, “pharmacokinetics”, “pharmacokinetic parameters”, “neuropathic pain”, and “randomized clinical trials”. The depth of the search was 26 years (from 1998 to 2024). This review resulted in 87 literature sources.Results. Neuropathic pain (NeP) is one of the most common types of chronic pain, characterized by a high prevalence among people of the working age. Effective pharmacotherapy aimed at eliminating the pain syndrome is a key tool for improving the quality of life and preserving the work capacity of patients. Heterogeneity of etiologic factors involved in the genesis of NeP indicates the need to use drugs the analgesic effect of which is based on weakening the transmission of pain impulses in the CNS. In clinical trials, gabapentin has demonstrated efficacy in reducing the severity of pain in patients with postherpetic NeP, painful diabetic neuropathy and many other conditions accompanied by NeP. The dose of gabapentin 300 mg/day is the initial dose in the therapy of NeP and requires a further slow titration depending on the patient’s response to therapy and tolerability of the drug, especially in elderly and senile patients, as well as in patients with an impaired renal function. According to the published data, the most pronounced analgesic effect is achieved in the patients against the background of the gabapentin administration at a dose of 3600 mg/day.Conclusion. Gabapentin is the drug of choice in the management of patients with NeP of different etiology and intensity. A satisfactory safety profile and pharmacodynamic effects make gabapentin possible, despite the long history of its use, to remain a relevant drug used by a wide range of physicians, specialties, for pharmacotherapy of NeP patients.

Painful diabetic peripheral neuropathy among Tunisian geriatric patients suffering from diabetes mellitus

Painful diabetic peripheral neuropathy among Tunisian geriatric patients suffering from diabetes mellitus

Prevalence and characteristics of painful diabetic neuropathy in patients with diabetes mellitus and normoalbuminuria

Prevalence and characteristics of painful diabetic neuropathy in patients with diabetes mellitus and normoalbuminuria

A Pain Physician’s Perspective on Recent Advances in Painful Diabetic Peripheral Neuropathy Management

Abstract Diabetic peripheral neuropathy (DPN) is a prevalent neurological complication linked to diabetes mellitus, exerting a substantial impact on the quality of life for those affected. This review article aims to discuss and review advances in the pain management of patients with DPN. We reviewed recent DPN management literature primarily from PubMed and SCOPUS using specific keywords, focusing on original research and recent advancements. The pathophysiology of DPN involves metabolic and vascular changes in nerve fibers, leading to direct damage and a decrease in their natural repair capacity. Effective glycemic control plays a central role in managing DPN, along with addressing other contributing factors such as comorbidities and lifestyle modifications. Nutraceuticals, including alpha-lipoic acid and Vitamin B12, have shown promising results in some studies. Antineuropathic agents such as calcium channel a2-δ ligands, serotonin and noradrenaline reuptake inhibitors, tricyclic antidepressants, and sodium channel blockers are commonly used in DPN pain management. Topical therapies, including capsaicin and lidocaine patches, have also demonstrated efficacy. Opioids are generally discouraged due to weak evidence and long-term deleterious side effects, along with the risk of addictive potential. Neuromodulation has emerged as a modality in resistant cases not responding to pharmacological management. Individualized treatment plans based on symptomatology, comorbidities, and side effect profiles should be developed for DPN patients. Comprehensive management of DPN involves a multidisciplinary approach, emphasizing patient education, regular assessment, and counseling to prevent further damage and complications.

Comparison of therapeutic effects of N-Acetylcysteine with pregabalin in improving the clinical symptoms of painful diabetic neuropathy: a randomized, double-blind clinical trial

ObjectivesPainful diabetic neuropathy (PDN) is highly prevalent and annoyingly in patients with diabetes. The aim of this study was to investigate the effects of oral N-acetylcysteine (NAC) compared to pregabalin in PDN.MethodsOne hundred two eligible patients with type 2 diabetes and PDN were randomly recievied pregabalin (150 mg/day) or N-Acetylcysteine (NAC) (600 mg/ twice a day) for 8 weeks. Mean pain score, Sleep interference score (SIS), Patient Global Impression of Change (PGIC), Clinical Global Impression of Change (CGIC), and also, serum levels of total antioxidant capacity (TAC), total thiol groups (TTG), catalase activity (CAT), nitric oxide (NO), and malondialdehyde (MDA) were assessed at baseline and at the end of the study.ResultsNAC was well tolerated in all patients. The decrease in mean pain scores and increase in SIS was similar between two groups. More improvement in PGIC and CGIC from the baseline was reported in NAC group. NAC, significantly, decreased serum levels of MDA, and NO, but increased TAC, TTG, and CAT. Pregabalin, significantly, decreased serum levels of MDA, and NO and increased TAC.DiscussionNAC is efficacious in alleviate symptoms of PDN which is probably related to its antioxidant effects.Trial registrationThe research protocol received approval from the Ethics Committee of Hamadan University of Medical Sciences (IR.UMSHA.REC.1397.137). The trial registry URL and number in Iranian Registry of Clinical Trials (IRCT): https://www.irct.ir/trial/33313, IRCT20180814040795N2 (Registration date: 2019-01-21, Retrospectively registered)

Comparison of the efficacy of spinal cord stimulation and dorsal root ganglion stimulation in the treatment of painful diabetic peripheral neuropathy: a prospective, cohort-controlled study.

The aim of this study was to compare the clinical outcomes of spinal cord stimulation (SCS) and dorsal root ganglion stimulation (DRG-S) in the treatment of painful diabetic peripheral neuropathy (PDPN). In this prospective cohort study, 55 patients received dorsal column spinal cord stimulation (SCS group) and 51 patients received dorsal root spinal cord stimulation (DRG-S group). The primary outcome was a Numerical Rating Scale (NRS) remission rate of ≥50%, and secondary outcomes included the effects of SCS and DRG-S on quality of life scores (EQ-5D-3L), nerve conduction velocity, and HbA1c, respectively. The percentage of NRS remission rate ≥ 50% at 6 months was 80.43 vs. 79.55%, OR (95% CI): 1.06 (0.38-2.97) in the SCS and DRG-S groups, respectively, and the percentage of VAS remission rate ≥ 50% at 12 months was 79.07 vs. 80.95%, OR (95% CI): 0.89 (0.31-2.58). Compared with baseline, there were significant improvements in EQ-5D and EQ-VAS at 6 and 12 months (p < 0.05), but there was no difference in improvement between the SCS and DRG-S groups (p > 0.05). Nerve conduction velocities of the common peroneal, peroneal, superficial peroneal, and tibial nerves were significantly improved at 6 and 12 months compared with the preoperative period in both the SCS and PND groups (p < 0.05). However, at 6 and 12 months, there was no difference in HbA1c between the two groups (p > 0.05). Both SCS and DRG-S significantly improved pain, quality of life, and lower extremity nerve conduction velocity in patients with PDPN, and there was no difference between the two treatments at 12 months.