Spinal Cord Stimulation for Painful Diabetic Peripheral Neuropathy: A Systematic Review.
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ABSTRACT:
SUBMITTER: Henson JV
PROVIDER: S-EPMC8586096 | biostudies-literature | 2021 Dec
REPOSITORIES: biostudies-literature
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Spinal Cord Stimulation for Painful Diabetic Peripheral Neuropathy: A Systematic Review.
Henson Josianna V JV Varhabhatla Narayana C NC Bebic Zvonimir Z Kaye Alan D AD Yong R Jason RJ Urman Richard D RD Merkow Justin S JS
Pain and therapy 20210710 2
Painful diabetic neuropathy is a common disease that results in significant pain and disability. Treatment options have traditionally consisted of conservative measures including topical and oral medication management as well as transcutaneous electrical stimulation units. These treatments demonstrate various degrees of efficacy, and many times initial treatments are discontinued, indicating low levels of satisfaction or poor tolerability. Spinal cord stimulation has been proposed as an alternat ...[more]
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Project description:BackgroundPainful Diabetic Peripheral Neuropathy (PDPN) is a common complication of diabetes, it severely affects the quality of life of patients. Acupuncture has been shown to be effective in the treatment of PDPN. To evaluate the efficacy and safety of acupuncture for pain relief in patients diagnosed with diabetic peripheral neuropathy, we conducted a systematic review and meta-analysis.MethodWe thoroughly searched specific databases, which included PUBMED, EMBASE, Web of Science, the Cochrane Library, the Chinese Biomedical Literature Database, the Chinese National Knowledge Infrastructure, China Science and Technology Journal Database and the Wanfang Data. All randomized controlled trials of acupuncture therapy for PDPN with pain change scales were included. Included studies were assessed for methodological quality according to the risk of bias from the Cochrane handbook. Meta-analyses were carried out to analyze the outcomes, subgroup analyses, sensitivity analyses, and funnel plot analyses were undertaken.ResultsThis systematic review evaluated a total of 25 trials of acupuncture therapy in combination with conventional treatment, involving a total of 1,561 patients with PDPN. According to the results, among 16 trials using VAS scores with a total of 1,552 patients, 2 acupoint injection trials (MD -2.38, 95% CI: -2.76 to -2.01, p < 0.00001), 12 acupuncture trials (MD -1. 31, 95% CI: -1.60 to -1.02, p < 0.00001) and 2 moxibustion trials showed that acupuncture therapy combined with conventional treatment improved pain better than conventional treatment (MD -2.50, 95% CI: -2.76 to -2.24, p < 0.00001). In the subgroup analysis of the acupuncture group, the results of the 5 trials in which the location of acupuncture was only in the limbs (MD -1.27, 95% CI: -1.54 to -1.01, p < 0.00001) and the 7 trials both in limbs and torso (MD -1.38, 95% CI: -1.81 to -0.95, p < 0.00001) also demonstrated that acupuncture was effective in pain improvement.ConclusionThis meta-analysis analyzed the possible efficacy of acupuncture in combination with conventional treatment for pain in diabetic peripheral neuropathy, particularly when acupoints are located in the limbs. However, there are limitations to this meta-analysis and future clinical studies are needed to confirm these findings.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023449447, identifier (CRD42023449447).
| S-EPMC10690617 | biostudies-literature
Project description:ImportanceMany patients with diabetic peripheral neuropathy experience chronic pain and inadequate relief despite best available medical treatments.ObjectiveTo determine whether 10-kHz spinal cord stimulation (SCS) improves outcomes for patients with refractory painful diabetic neuropathy (PDN).Design, setting, and participantsThe prospective, multicenter, open-label SENZA-PDN randomized clinical trial compared conventional medical management (CMM) with 10-kHz SCS plus CMM. Participants with PDN for 1 year or more refractory to gabapentinoids and at least 1 other analgesic class, lower limb pain intensity of 5 cm or more on a 10-cm visual analogue scale (VAS), body mass index (calculated as weight in kilograms divided by height in meters squared) of 45 or less, hemoglobin A1c (HbA1c) of 10% or less, daily morphine equivalents of 120 mg or less, and medically appropriate for the procedure were recruited from clinic patient populations and digital advertising. Participants were enrolled from multiple sites across the US, including academic centers and community pain clinics, between August 2017 and August 2019 with 6-month follow-up and optional crossover at 6 months. Screening 430 patients resulted in 214 who were excluded or declined participation and 216 who were randomized. At 6-month follow-up, 187 patients were evaluated.InterventionsImplanted medical device delivering 10-kHz SCS.Main outcomes and measuresThe prespecified primary end point was percentage of participants with 50% pain relief or more on VAS without worsening of baseline neurological deficits at 3 months. Secondary end points were tested hierarchically, as prespecified in the analysis plan. Measures included pain VAS, neurological examination, health-related quality of life (EuroQol Five-Dimension questionnaire), and HbA1c over 6 months.ResultsOf 216 randomized patients, 136 (63.0%) were male, and the mean (SD) age was 60.8 (10.7) years. Additionally, the median (interquartile range) duration of diabetes and peripheral neuropathy were 10.9 (6.3-16.4) years and 5.6 (3.0-10.1) years, respectively. The primary end point assessed in the intention-to-treat population was met by 5 of 94 patients in the CMM group (5%) and 75 of 95 patients in the 10-kHz SCS plus CMM group (79%; difference, 73.6%; 95% CI, 64.2-83.0; P < .001). Infections requiring device explant occurred in 2 patients in the 10-kHz SCS plus CMM group (2%). For the CMM group, the mean pain VAS score was 7.0 cm (95% CI, 6.7-7.3) at baseline and 6.9 cm (95% CI, 6.5-7.3) at 6 months. For the 10-kHz SCS plus CMM group, the mean pain VAS score was 7.6 cm (95% CI, 7.3-7.9) at baseline and 1.7 cm (95% CI, 1.3-2.1) at 6 months. Investigators observed neurological examination improvements for 3 of 92 patients in the CMM group (3%) and 52 of 84 in the 10-kHz SCS plus CMM group (62%) at 6 months (difference, 58.6%; 95% CI, 47.6-69.6; P < .001).Conclusions and relevanceSubstantial pain relief and improved health-related quality of life sustained over 6 months demonstrates 10-kHz SCS can safely and effectively treat patients with refractory PDN.Trial registrationClincalTrials.gov Identifier: NCT03228420.
| S-EPMC8022268 | biostudies-literature
Project description:BACKGROUND: Diabetic peripheral neuropathy, a common comorbidity of diabetes, is a neurodegenerative disorder that targets sensory, autonomic, and motor nerves frequently associated with painful diabetic neuropathy (PDN). PDN carries an economic burden as the result of reduced work and productivity. A recent multicenter randomized controlled trial, SENZA-PDN (NCT03228420), assessed the impact of high-frequency (10 kHz) spinal cord stimulation (SCS) on pain relief. The effects of high-frequency SCS on health care resource utilization and medical costs are not known. OBJECTIVE: To evaluate the effect of high-frequency (10 kHz) SCS on health care resource utilization (HRU) and medical costs in patients with PDN using data from the SENZA-PDN trial. METHODS: Participants with PDN were randomly assigned 1:1 to receive either 10 kHz SCS plus conventional medical management (CMM) (SCS treatment group) or CMM alone (CMM treatment group). Patient outcomes and HRU up to the 6-month follow-up are reported here. Costs (2020 USD) for each service was estimated based on publicly available Medicare fee schedules, Medicare claims data, and literature. HRU metrics of inpatient and outpatient contacts and costs are reported as means and SDs. Univariate and bivariate analyses were used to compare SCS and CMM treatment groups at 6 months. RESULTS: At 6-month follow up, the SCS arm experienced approximately half the mean rate of hospitalizations per patient compared with the CMM treatment group (0.08 vs 0.15; P = 0.066). The CMM treatment group's total health care costs per patient were approximately 51% higher compared with the SCS treatment group (equivalent to mean annual cost per patient of $9,532 vs $6,300). CONCLUSIONS: Our analysis of the SENZA-PDN trial indicates that the addition of 10 kHz SCS therapy results in lower rates of hospitalization and consequently lower health care costs among patients with PDN compared with those receiving conventional management alone.
| S-EPMC10508838 | biostudies-literature
Project description:Spinal cord stimulation (SCS) is increasingly used to treat painful diabetic neuropathy (PDN). At the time of a recent meta-analysis in this field, data were only available from randomized controlled trials (RCTs) of traditional low-frequency SCS (LF-SCS). However, outcomes from high-frequency 10 kHz SCS treatment are now available. Our study aimed to systematically review the contemporary evidence for SCS in patients with lower limb pain due to PDN and include an indirect comparison of the high- and low-frequency modalities. We searched the PubMed/CENTRAL databases up to 18 August 2022, for peer-reviewed RCTs of SCS that enrolled PDN patients with lower limb pain symptoms. The quality of the evidence was assessed with the Cochrane Risk of Bias tool. Using SCS treatment arm data from the RCTs, we indirectly compared the absolute treatment effect of 10 kHz SCS and LF-SCS. Results are presented in tables and forest plots. This systematic review was reported according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 guidelines. Three RCTs met our eligibility criteria, including the recent 10 kHz SCS RCT (N = 216, 90 implanted) and 2 others that examined LF-SCS (N = 36, 17 implanted; N = 60, 37 implanted). Our analysis of 6-month data found clinically meaningful pain relief with each SCS modality. However, significantly greater pain reduction was identified for 10 kHz SCS over LF-SCS: average pain reduction in the 10 kHz SCS cohort was 73.7% compared with 47.5% in the pooled LF-SCS group (p < 0.0001). In the permanent implant subset, the 50% pain reduction responder rate was 83.3% in the 10 kHz SCS cohort versus 63.0% in the pooled LF-SCS group (p = 0.0072). The overall risk of bias of each included RCT was deemed high, mainly due to the absence of patient blinding. Our analysis indicates that paresthesia-free 10 kHz SCS can provide superior pain relief and responder rate over LF-SCS for managing PDN patients refractory to conventional medical management.
| S-EPMC9599433 | biostudies-literature
Project description:Diabetic Peripheral Neuropathy (DPN) typically is accompanied by painful symptoms. Several therapeutic agents have been tried for symptomatic relief, but with varying results. The use of non-invasive neuromodulation (NINM) is a potential treatment option for DPN. The objective of our study is to evaluate NINM effects on pain rating and nerve conduction velocity in DPN patients. The search was carried out in seven databases until Aug 30th, 2019. Finally, twenty studies met the inclusion criteria. We found a significant reduction of pain scores by central NINMs (effect size [ES] = - 0.75, 95% CI = - 1.35 to - 0.14), but not by the overall peripheral techniques (electrical and electromagnetic) (ES = - 0.58, 95% CI = - 1.23 to 0.07). However, the subgroup of peripheral electrical NINMs reported a significant higher effect (ES = - 0.84, 95% CI = - 1.57 to - 0.11) compared to electromagnetic techniques (ES = 0.21; 95% CI = - 1.00 to 1.42, I2 = 95.3%) . Other subgroup analysis results show that NINMs effects are higher with intensive protocols and in populations with resistant symptoms or intolerance to analgesic medications. Besides, NINMs can increase motor nerves velocity (ES = 1.82; 95% CI = 1.47 to 2.17), and there were no effects on sensory nerves velocity (ES = 0.01, 95% CI = - 0.79 to 0.80). The results suggest that central and peripheral electrical NINMs could reduce neuropathic pain among DPN patients, without reported adverse events. Well-powered studies are needed to confirm that NINM techniques as an alternative effective and safe treatment option.
| S-EPMC7645738 | biostudies-literature
Project description:Impaired rate-dependent depression (RDD) of the Hoffman reflex is associated with reduced dorsal spinal cord potassium chloride cotransporter expression and impaired spinal γ-aminobutyric acid type A receptor function, indicative of spinal inhibitory dysfunction. We have investigated the pathogenesis of impaired RDD in diabetic rodents exhibiting features of painful neuropathy and the translational potential of this marker of spinal inhibitory dysfunction in human painful diabetic neuropathy. Impaired RDD and allodynia were present in type 1 and type 2 diabetic rats but not in rats with type 1 diabetes receiving insulin supplementation that did not restore normoglycemia. Impaired RDD in diabetic rats was rapidly normalized by spinal delivery of duloxetine acting via 5-hydroxytryptamine type 2A receptors and temporally coincident with the alleviation of allodynia. Deficits in RDD and corneal nerve density were demonstrated in patients with painful diabetic neuropathy compared with healthy control subjects and patients with painless diabetic neuropathy. Spinal inhibitory dysfunction and peripheral small fiber pathology may contribute to the clinical phenotype in painful diabetic neuropathy. Deficits in RDD may help identify patients with spinally mediated painful diabetic neuropathy who may respond optimally to therapies such as duloxetine.
| S-EPMC5399611 | biostudies-literature
Project description:Diabetic peripheral neuropathy (DPN) is a common disabling complication of diabetes. Almost half of the patients with DPN develop neuropathic pain (NeuP) for which current analgesic treatments are inadequate. Understanding the role of genetic variability in the development of painful DPN is needed for improved understanding of pain pathogenesis for better patient stratification in clinical trials and to target therapy more appropriately. Here, we examined the relationship between variants in the voltage-gated sodium channel NaV1.7 and NeuP in a deeply phenotyped cohort of patients with DPN. Although no rare variants were found in 78 participants with painless DPN, we identified 12 rare NaV1.7 variants in 10 (out of 111) study participants with painful DPN. Five of these variants had previously been described in the context of other NeuP disorders and 7 have not previously been linked to NeuP. Those patients with rare variants reported more severe pain and greater sensitivity to pressure stimuli on quantitative sensory testing. Electrophysiological characterization of 2 of the novel variants (M1852T and T1596I) demonstrated that gain of function changes as a consequence of markedly impaired channel fast inactivation. Using a structural model of NaV1.7, we were also able to provide further insight into the structural mechanisms underlying fast inactivation and the role of the C-terminal domain in this process. Our observations suggest that rare NaV1.7 variants contribute to the development NeuP in patients with DPN. Their identification should aid understanding of sensory phenotype, patient stratification, and help target treatments effectively.
| S-EPMC5828379 | biostudies-literature
Project description:BackgroundPainful diabetic neuropathy (PDN) is one of the major complications of diabetes mellitus. It is often debilitating and refractory to pharmaceutical therapies. Our goal was to systematically review and evaluate the strength of evidence of interventional management options for PDN and make evidence-based recommendations for clinical practice.MethodsWe searched PubMed, Scopus, Google Scholar, and Cochrane Llibrary and systematically reviewed all types of clinical studies on interventional management modalities for PDN.ResultsWe identified and analyzed 10 relevant randomized clinical trials (RCTs), 8 systematic reviews/meta-analyses, and 5 observational studies of interventional modalities for PDN using pain as primary outcome. We assessed the risk of bias in grading of evidence and found that there is moderate to strong evidence to support the use of dorsal column spinal cord stimulation (SCS) in treating PDN in the lower extremities (evidence level: 1B+), while studies investigating its efficacy in the upper extremities are lacking. Evidence exists that acupuncture and injection of botulinum toxin-A provide relief in pain or muscle cramps due to PDN with minimal side effects (2B+/1B+). Similar level of evidence supports surgical decompression of lower limb peripheral nerves in patients with intractable PDN and superimposed nerve compression (2B±/1B+). Evidence for sympathetic blocks or neurolysis and dorsal root ganglion (DRG) stimulation is limited to case series (2C+).ConclusionsModerate to strong evidence exists to support the use of SCS in managing lower extremity pain in patients who have failed conventional medical management for PDN. Acupuncture or injection of botulinum toxin-A can be considered as an adjunctive therapy for PDN. Surgical decompression of peripheral nerves may be considered in patients with PDN superimposed with nerve compression. High-quality studies are warranted to further evaluate the safety, efficacy, and cost-effectiveness of interventional therapies for PDN.
| S-EPMC9124666 | biostudies-literature
Project description:BACKGROUND:Painful diabetic neuropathy (PDN), a debilitating and progressive chronic pain condition that significantly impacts quality of life, is one of the common complications seen with long-standing diabetes mellitus. Neither pharmacological treatments nor low-frequency spinal cord stimulation (SCS) has provided significant and long-term pain relief for patients with PDN. This study aims to document the value of 10-kHz SCS in addition to conventional medical management (CMM) compared with CMM alone in patients with refractory PDN. METHODS:In a prospective, multicenter, randomized controlled trial (SENZA-PDN), 216 subjects with PDN will be assigned 1:1 to receive 10-kHz SCS combined with CMM or CMM alone after appropriate institutional review board approvals and followed for 24 months. Key inclusion criteria include (1) symptoms of PDN for at least 12 months, (2) average pain intensity of at least 5 cm-on a 0- to 10-cm visual analog scale (VAS)-in the lower limbs, and (3) an appropriate candidate for SCS. Key exclusion criteria include (1) large or gangrenous ulcers or (2) average pain intensity of at least 3 cm on VAS in the upper limbs or both. Along with pain VAS, neurological assessments, health-related quality of life, sleep quality, and patient satisfaction will be captured. The primary endpoint comparing responder rates (≥50% pain relief) and safety rates between the treatment groups will be assessed at 3 months. Several secondary endpoints will also be reported on. DISCUSSION:Enrollment commenced in 2017 and was completed in 2019. This study will help to determine whether 10-kHz SCS improves clinical outcomes and health-related quality of life and is a cost-effective treatment for PDN that is refractory to CMM. TRIAL REGISTRATION:ClincalTrials.gov identifier: NCT03228420 (registered 24 July 2017).
| S-EPMC6961392 | biostudies-literature
Project description:Peripheral neuropathy is a frequent complication of type 2 diabetes mellitus (T2DM). We investigated whether human islet amyloid polypeptide (hIAPP), which forms pathogenic aggregates that damage pancreatic islet β cells in T2DM, is involved in T2DM-associated peripheral neuropathy. In vitro, hIAPP incubation with sensory neurons reduced neurite outgrowth and increased levels of mitochondrial reactive oxygen species. hIAPP-transgenic mice, which have elevated plasma hIAPP levels without hyperglycemia, developed peripheral neuropathy as evidenced by pain-associated behavior and reduced intraepidermal nerve fiber (IENF) density. Similarly, hIAPP Ob/Ob mice, which have hyperglycemia in combination with elevated plasma hIAPP levels, had signs of neuropathy, although more aggravated. In wild-type mice, intraplantar and intravenous hIAPP injections induced long-lasting allodynia and decreased IENF density. Non-aggregating murine IAPP, mutated hIAPP (pramlintide), or hIAPP with pharmacologically inhibited aggregation did not induce these effects. T2DM patients had reduced IENF density and more hIAPP oligomers in the skin compared with non-T2DM controls. Thus, we provide evidence that hIAPP aggregation is neurotoxic and mediates peripheral neuropathy in mice. The increased abundance of hIAPP aggregates in the skin of T2DM patients supports the notion that hIAPP is a potential contributor to T2DM neuropathy in humans.
| S-EPMC10104883 | biostudies-literature