Painful Peripheral Neuropathy Research Articles

Status of Analgesic Drugs and Quality of Life Results for Diabetic Peripheral Neuropathy in China.

ObjectiveThe purpose of this study is to describe the current clinical situation of patients with painful diabetic peripheral neuropathy (DPN) and related anxiety, depression, and the quality of life of patients in mainland China, and to report the current status of the use of analgesics.MethodsBetween June 15, 2021, and October 15, 2021, a total of 401 participants participated in the study. Recruitment was carried out using a multi-level sampling method. Participants’ demographics, medical history, analgesic use, Michigan Symptom Score (MNSI), Numerical Rating Scale (NRS) pain score, Patient Health Questionnaire 9 (PHQ-9) score, Generalized Anxiety Disorder 7 (GAD) -7) Score, quality of life score (SF-12) and diabetes treatment status were collected.ResultsAmong the participants, there were 236 male patients and female patients. Participants were 322 patients over 40 years old. Regarding the use of analgesics: 132 patients reported using analgesics, 221 patients reported not using analgesics, and 48 patients reported having used analgesics. The results of the scale showed that the scores of NRS, GAD-7, PHQ-9 and SF-12 were 5.12 ± 2.15, 6.33 ± 3.67, 8.46 ± 4.07 and 47.84 ± 19.92 for patients who used analgesics, Compared with patients who did not use analgesics (NRS: 1.99 ± 1.7, GAD-7: 1.81 ± 2.81, PHQ-9: 3.13 ± 4.10, SF-12: 78.34 ± 21.66) there are significant differences (p< 0.001). In addition, patients’ NRS scores are also closely related to GAD-7, PHQ-9 and SF-12 scores.ConclusionThe severity of symptoms, mental status and quality of life of patients who used analgesics were more severe than those of patients who did not use analgesics. Pregabalin is still the preferred analgesic for patients with painful DPN, and the use of opioids in my country is extremely low, which is consistent with current international guidelines. Age, diabetic duration, DPN duration, PHQ-9 score, GAD-7 score and SF-12 scores are closely related to NRS pain scores. In addition, there are still a considerable number of patients who have not used analgesics due to financial burdens and other reasons, suggesting that China still has insufficient pain management in DPN patients.

Increased Pain Symptomatology Among Females vs. Males With Fragile X-Associated Tremor/Ataxia Syndrome.

Individuals with the fragile X premutation report symptoms of chronic pain from multiple systems, have increased incidence of comorbid conditions where pain is a prominent feature, and pathophysiology that supports disrupted pain regulation, inflammation, and energy imbalance. Less is known about how pain manifests for the subpopulation of carriers that develop the motor and cognitive changes of fragile X-associated tremor and ataxia syndrome (FXTAS), and how pain may differ between men and women. We gathered data collected from 104 males and females with FXTAS related to chronic pain, comorbid conditions related to pain, and medications used for pain control to further explore the types of pain experienced and to better characterize how individuals with the fragile X premutation experience pain sensation across genders. We found that women experience significantly more pain symptoms than men, particularly allodynia (20 vs. 2.0%, p = 0.008), peripheral neuropathy pain (43.9 vs. 25.4%, p = 0.0488), migraine (43.9 vs. 14.5%, p = 0.0008), fibromyalgia (26.8 vs. 0%, p = 0.0071) and back pain (48.5 vs. 23.4%, p = 0.008). We found onset of peripheral neuropathy predicts the onset of ataxia (β = 0.63 ± 0.25, p = 0.019) and tremor (β = 0.56 ± 0.17, p = 0.004) across gender. Women also report significantly more anxiety (82.9 vs. 39.7%, p < 0.001), which has implications for ideal pain treatment. These pain symptoms need to be recognized in the medical history and treated appropriately, with consideration for overlapping comorbidities.

Dual PI3Kδ/γ Inhibitor Duvelisib Prevents Development of Neuropathic Pain in Model of Paclitaxel-Induced Peripheral Neuropathy.

The development of painful paclitaxel-induced peripheral neuropathy (PIPN) represents a major dose-limiting side effect of paclitaxel chemotherapy. Here we report a promising effect of duvelisib (Copiktra), a novel FDA-approved PI3Kδ/γ isoform-specific inhibitor, in preventing paclitaxel-induced pain-like behavior and pronociceptive signaling in DRGs and spinal cord dorsal horn (SCDH) in rat and mouse model of PIPN. Duvelisib blocked the development of mechanical hyperalgesia in both males and females. Moreover, duvelisib prevented paclitaxel-induced sensitization of TRPV1 receptors, and increased PI3K/Akt signaling in small-diameter DRG neurons and an increase of CD68+ cells within DRGs. Specific optogenetic stimulation of inhibitory neurons combined with patch-clamp recording revealed that duvelisib inhibited paclitaxel-induced weakening of inhibitory, mainly glycinergic control on SCDH excitatory neurons. Enhanced excitatory and reduced inhibitory neurotransmission in the SCDH following PIPN was also alleviated by duvelisib application. In summary, duvelisib showed a promising ability to prevent neuropathic pain in PIPN. The potential use of our findings in human medicine may be augmented by the fact that duvelisib is an FDA-approved drug with known side effects.SIGNIFICANCE STATEMENT We show that duvelisib, a novel FDA-approved PI3Kδ/γ isoform-specific inhibitor, prevents the development of paclitaxel-induced pain-like behavior in males and females and prevents pronociceptive signaling in DRGs and spinal cord dorsal horn in rat and mouse model of paclitaxel-induced peripheral neuropathy.

Mapping the Journey of Patients with Painful Diabetic Peripheral Neuropathy in the Philippines.

Knowing the limited epidemiological studies on painful diabetic peripheral neuropathy (pDPN) in the Philippines, the present review aimed to map the prevalence of pDPN and identify the associated healthcare gaps. A systematic search of MEDLINE, Embase and BIOSIS was conducted using predefined inclusion criteria, and relevant studies published in English between 2004 and 2021 were identified. An unstructured literature search was also conducted on public and government websites with no date restriction. Data combined from all sources were synthesized and presented as a simple mean. Three studies were considered for final analyses of the 26 articles retrieved from structured and unstructured searches. The sample sizes for the three studies were 103, 172, and 100, respectively. The simple mean prevalence of pDPN was estimated at 26.5%. Awareness of pDPN based on a published study was 89%. According to published studies, screening and diagnosis of pDPN were 65% and 76.7%, respectively. One-third of the patients with pDPN (75%) were treated. No literature is available for adherence and control. Limited data exist on the different management stages of patients with pDPN in the Philippines. The study analysis will help address the knowledge gaps, improve patient care and pain management, and aid decision making.

Diagnosis and Treatment of Painful Diabetic Peripheral Neuropathy

This monograph offers clinicians up-to-date, evidence-based information regarding the mechanisms involved in inducing nerve fiber damage and neuropathic pain and the spectrum of risk factors and DPN pheno-types across the life span, as well as a novel discussion of the impact of social determinants of health (SDOH) on DPN development and management. It also provides busy clinicians with a customized, stepwise approach to effectively screen for and diagnose DPN in routine care. Additionally, it summarizes the latest guidance on effective pharmacological and nonpharmacological therapeutic strategies for painful DPN, including the respective roles of nutraceutical products, dietary modification, exercise, and new technologies. Finally, this publication outlines knowledge gaps that need to be targeted to identify modifiable risk factors, develop more sensitive assessments, and produce effective therapies to either prevent the progression of or reverse neuropathic disease. It advocates a personalized care approach to ultimately reduce sequelae and the related health care burden and optimize quality of life for people with diabetes and DPN.

Effectiveness and safety of amitriptyline, duloxetine, and pregabalin in painful diabetic neuropathy: An observational study

Background: Studies comparing the real-world effectiveness, safety, and effect on quality of life (QoL) of drugs for painful diabetic peripheral neuropathy (DPN) are scarce. Aims and Objectives: The aim of the study was to compare effectiveness, safety and effect on QoL of amitriptyline (AMY), duloxetine (DUL) and pregabalin (PGN) in DPN. Materials and Methods: After ethics committee approval and informed consent, 75 outpatients (25 each) prescribed any one of above drugs were consecutively recruited in a prospective and observational study. Drug effectiveness was assessed by comparing difference in mean monthly visual analogue scale (VAS) score from baseline, obtained from pain diary. QoL was assessed by comparing total and domain-wise score on Nottingham health profile (NHP) questionnaire. Safety was assessed by comparing frequency of adverse drug reactions (ADRs). Qualitative and quantitative outcome measures were compared using Chi-square test and one-way analysis of variance, respectively. P &lt; 0.05 was considered statistically significant. Results: The difference in mean monthly VAS scores at the end of 4, 8, and 12 weeks was similar between the three drugs. Patients on PGN had smaller beneficial effects in total as well as emotional, energy, and sleep domains of NHP compared to other drugs. Sedation and dizziness occurred with all drugs but PGN had least incidence of sedation. Conclusion: AMY, DUL and PGN are equally effective and safe in DPN. Although PGN did not improve QoL unlike AMY and DUL, it had lower incidence of sedation.

A review of the neurological complications of breast cancer.

Conducting broad assessments of the main burden of breast cancer is the core factor for improving overdiagnosis and overtreatment of breast cancer patients as well as their survival rates. Breast cancer patients may experience neurological complications that cause devastating effects on them. Chemotherapy-induced peripheral neuropathy (CIPN) and neuropathic pain are two of the most reported complications. Objective: This study aims to review the neurological complications of breast cancer and the ways to control and treat them. Comprehensive searches were carried out about the keywords of Breast Cancer, Neurological Complications, and Breast Cancer Consequences. These keywords were searched through the most well-known databases of MEDLINE, PUBMED, Cochrane Library, Best Evidence, CancerLit, HealthSTAR, and LegalTrac. In this regard, 83 articles were chosen to be included in this study from 2010 to 2021. The identification and treatment process of neurologic syndromes are not easy. The main neurologic syndromes which the breast cancer patients face are opsoclonus myoclonus syndrome (OMS), encephalitis, sensorimotor neuropathy, retinopathy, cerebellar degeneration, and stiff-person's syndrome. CIPN and neuropathic pain are among the most prevalent side effects which are categorized as neurological complications and mainly seen 1 year after the management of breast cancer. Aiming to minimize the burden following the treatment of breast cancer, these complications should be diagnosed and treated accurately.

An Analysis of Peripheral Neuropathy Symptom Characteristics in HIV.

Objectives:A gap remains in understanding the association among the symptoms of distal sensory peripheral neuropathy (DSPN) (pain, aching, burning, pins and needles, numbness), comorbidities, and medication use among persons living with People Living with HIV/AIDS (PLWH) with DSPN. This report describes the symptom characteristics associated with prescribed treatment regimens (HIV and non-HIV medications) and comorbidities from a cohort of PLWH experiencing symptoms of DSPN who reside in New York City.Methods:Our sample (n=353) included PLWH who were 18 years or older, and with painful lower limb (LL) peripheral neuropathy screened for an ongoing clinical trial to reduce DSPN symptoms using acupuncture/moxibustion. The trial participants completed a screening interview where they reported age, gender, race, ethnicity, HIV status, presence of LL DSPN and DSPN symptoms, current medications, and comorbidities.Results:Of 465 persons screened, 353 provided information for inclusion in this analysis. Seventy-eight percent rated their LL DSPN in the “severe” or “very severe” discomfort/pain range. Nearly half of those were taking prescribed or over-the-counter medication, such as nonnarcotic analgesics, antidepressants, and anticonvulsants, to manage their DSPN discomfort/pain. Despite the use of OTC and or prescription pain relievers, participants reported insufficient symptom relief.Discussion:Combination Antiretroviral Therapies (CART) effectively control viral load and maintain healthy T-cell levels in individuals with HIV. It has made HIV a chronic disease for many. However, HIV DPSN remains prevalent and has a negative impact on the lives of PLWH. Our findings highlight that, despite the availability and the use of CART, DSPN remains prevalent and not well managed. A critical need exists for the development of effective interventions to manage DSPN symptoms.

The Effect of Anakinra on Acrylamide-induced Peripheral Neuropathy and Neuropathic Pain in Rats

Acrylamide is a neurotoxic compound. Moreover, anakinra is an interleukin-1 (IL-1) receptor antagonist used in rheumatoid arthritis treatment. This study investigated the effect of anakinra on acrylamide-related neuropathy and neuropathic pain. Acrylamide exposure caused a significant decrease in the pain threshold; an increase in malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β) levels; and a decrease in total glutathione (tGSH) values in the sciatic nerve. This indicates hyperalgesia presence, oxidative stress, and peripheral nerve tissue inflammation. Anakinra treatment significantly reduced the MDA, IL-1β, and TNF-α levels, and increased the pain threshold and mean tGSH values. The analgesic effect of anakinra was 67.9% at the first hour, increasing to 74.9% and 76.7% at the second and third hours, respectively. The group receiving acrylamide exhibited histopathological changes (e.g., swollen and degenerated axons, hypertrophic and hyperplasic Schwann cells, and congested vessels). The use of anakinra significantly improved these morphological changes. Anakinra is concluded to reduce neuropathic pain and prevent neurotoxic effect of acrylamide on peripheral nerves due to its analgesic, antioxidant, and anti-inflammatory properties.

Diabetic Peripheral Neuropathy.

Diabetic painless and painful peripheral neuropathy remains the most frequent complication of diabetes mellitus, but the pathophysiology remains undescribed, there are no robust clinical endpoints and no efficient treatment exists. This hampers good clinical practice, fruitful clinical research and successful pharmacological trials, necessary for the development of early detection, prevention and treatment. This chapter supplies an update on background and treatment of diabetic peripheral neuropathy. Goals and perspectives for future clinical and scientific approaches are also described.

Potamogeton perfoliatus L. Extract Attenuates Neuroinflammation and Neuropathic Pain in Sciatic Nerve Chronic Constriction Injury-Induced Peripheral Neuropathy in Rats.

Sciatic nerve injury is often associated with neuropathic pain and neuroinflammation in the central and peripheral nervous systems. In our previous work, Potamogeton perfoliatus L. displayed anti-inflammatory, antipyretic and analgesic properties, predominantly via the inhibition of COX-2 enzyme and attenuation of oxidative stress. Herein, we extended our investigations to study the effects of the plant’s extract on pain-related behaviors, oxidative stress, apoptosis markers, GFAP, CD68 and neuro-inflammation in sciatic nerve chronic constriction injury (CCI) rat model. The levels of the pro-inflammatory marker proteins in sciatic nerve and brainstem were measured with ELISA 14 days after CCI induction. Pretreatment with the extract significantly attenuated mechanical and cold allodynia and heat hyperalgesia with better potential than the reference drug, pregabalin. In addition, CCI lead to the overexpression of prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS), tumor necrosis alpha (TNFα), nuclear factor κB (NF-κB), cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX), and NADPH oxidase-1 (NOX-1) and decreased the catalase level in sciatic nerve and brainstem. The observed neuro-inflammatory changes were accompanied with glial cells activation (increased GFAP and CD68 positive cells), apoptosis (increased Bax) and structural changes in both brainstem and sciatic nerve. The studied extract attenuated the CCI-induced neuro-inflammatory changes, oxidative stress, and apoptosis while it induced the expression of Bcl-2 and catalase in a dose dependent manner. It also decreased the brainstem expression of CD68 and GFAP indicating a possible neuroprotection effect. Taking together, P. perfoliatus may be considered as a novel therapy for neuropathic pain patients after performing the required clinical trials.

Characterization of Patients With and Without Painful Peripheral Neuropathy After Receiving Neurotoxic Chemotherapy: Traditional Quantitative Sensory Testing vs C-Fiber and Aδ-Fiber Selective Diode Laser Stimulation

Painful chemotherapy induced peripheral neuropathy (CIPN) is a common complication of chemotherapy with drugs such as taxanes and platinum compounds. Currently, no methods are available for early detection of sensory changes that are associated with painful CIPN, nor are there biomarkers that are specific to painful CIPN. This study aimed to compare Diode Laser fiber type-selective stimulator (DLss), a method to selectively stimulate cutaneous C and Aδ fibers, to traditional quantitative sensory testing (QST) in determining psychophysical differences between patients with painful CIPN and a control group. Sensory testing was performed on the dorsal mid-foot of 20 patients with painful neuropathy after taxane- or platinum-based chemotherapy, and 20 patients who received similar neurotoxic chemotherapy, without painful CIPN. In a multivariable analysis, C-fiber to Aδ fiber detection threshold ratio, measured by DLss, was significantly different between the groups (P <.05). While QST parameters such as warmth detection threshold were different between the groups in univariate analyses, these findings were likely attributable to group differences in patient age and cumulative chemotherapy dose. PerspectiveIn this study, fiber-specific DLss test showed potential in identifying sensory changes that are specific for painful neuropathy, encouraging future testing of this approach as a biomarker for early detection of painful CIPN. Trial registrationThe study was approved by the Washington University Institutional Review Board (#201807162) and registered at ClinicalTrials.gov (NCT03687970).

Keratinocyte Biomarkers Distinguish Painful Diabetic Peripheral Neuropathy Patients and Correlate With Topical Lidocaine Responsiveness.

This study investigated quantifiable measures of cutaneous innervation and algesic keratinocyte biomarkers to determine correlations with clinical measures of patient pain perception, with the intent to better discriminate between diabetic patients with painful diabetic peripheral neuropathy (PDPN) compared to patients with low-pain diabetic peripheral neuropathy (lpDPN) or healthy control subjects. A secondary objective was to determine if topical treatment with a 5% lidocaine patch resulted in correlative changes among the quantifiable biomarkers and clinical measures of pain perception, indicative of potential PDPN pain relief. This open-label proof-of-principle clinical research study consisted of a pre-treatment skin biopsy, a 4-week topical 5% lidocaine patch treatment regimen for all patients and controls, and a post-treatment skin biopsy. Clinical measures of pain and functional interference were used to monitor patient symptoms and response for correlation with quantitative skin biopsy biomarkers of innervation (PGP9.5 and CGRP), and epidermal keratinocyte biomarkers (Nav1.6, Nav1.7, CGRP). Importantly, comparable significant losses of epidermal neural innervation (intraepidermal nerve fibers; IENF) and dermal innervation were observed among PDPN and lpDPN patients compared with control subjects, indicating that innervation loss alone may not be the driver of pain in diabetic neuropathy. In pre-treatment biopsies, keratinocyte Nav1.6, Nav1.7, and CGRP immunolabeling were all significantly increased among PDPN patients compared with control subjects. Importantly, no keratinocyte biomarkers were significantly increased among the lpDPN group compared with control. In post-treatment biopsies, the keratinocyte Nav1.6, Nav1.7, and CGRP immunolabeling intensities were no longer different between control, lpDPN, or PDPN cohorts, indicating that lidocaine treatment modified the PDPN-related keratinocyte increases. Analysis of the PDPN responder population demonstrated that increased pretreatment keratinocyte biomarker immunolabeling for Nav1.6, Nav1.7, and CGRP correlated with positive outcomes to topical lidocaine treatment. Epidermal keratinocytes modulate the signaling of IENF, and several analgesic and algesic signaling systems have been identified. These results further implicate epidermal signaling mechanisms as modulators of neuropathic pain conditions, highlight a novel potential mode of action for topical treatments, and demonstrate the utility of comprehensive skin biopsy evaluation to identify novel biomarkers in clinical pain studies.

Neuroendocrine Stress Axis-Dependence of Duloxetine Analgesia (Anti-Hyperalgesia) in Chemotherapy-Induced Peripheral Neuropathy

Duloxetine, a serotonin and norepinephrine reuptake inhibitor, is the best-established treatment for painful chemotherapy-induced peripheral neuropathy (CIPN). While it is only effective in little more than half of patients, our ability to predict patient response remains incompletely understood. Given that stress exacerbates CIPN, and that the therapeutic effect of duloxetine is thought to be mediated, at least in part, via its effects on adrenergic mechanisms, we evaluated the contribution of neuroendocrine stress axes, sympathoadrenal and hypothalamic-pituitary-adrenal, to the effect of duloxetine in preclinical models of oxaliplatin- and paclitaxel-induced CIPN. Systemic administration of duloxetine, which alone had no effect on nociceptive threshold, both prevented and reversed mechanical hyperalgesia associated with oxaliplatin- and paclitaxel-CIPN. It more robustly attenuated oxaliplatin CIPN in male rats, while it was more effective for paclitaxel CIPN in females. Gonadectomy attenuated these sex differences in the effect of duloxetine. To assess the role of neuroendocrine stress axes in the effect of duloxetine on CIPN, rats of both sexes were submitted to adrenalectomy combined with fixed level replacement of corticosterone and epinephrine. While CIPN, in these rats, was of similar magnitude to that observed in adrenal-intact animals, rats of neither sex responded to duloxetine. Furthermore, duloxetine blunted an increase in corticosterone induced by oxaliplatin, and prevented the exacerbation of CIPN by sound stress. Our results demonstrate a role of neuroendocrine stress axes in duloxetine analgesia (anti-hyperalgesia) for the treatment of CIPN.SIGNIFICANCE STATEMENT Painful chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating dose-dependent and therapy-limiting side effect of many of the cytostatic drugs used to treat cancer (Argyriou et al., 2010; Marmiroli et al., 2017). Duloxetine is the only treatment for CIPN currently recommended by the American Society of Clinical Oncology (Hershman et al., 2014). In the present study, focused on elucidating mechanisms mediating the response of oxaliplatin- and paclitaxel-induced painful peripheral neuropathy to duloxetine, we demonstrate a major contribution to its effect of neuroendocrine stress axis function. These findings, which parallel the clinical observation that stress may impact response of CIPN to duloxetine (Taylor et al., 2007), open new approaches to the treatment of CIPN and other stress-associated pain syndromes.

Botulinum Toxin Type A for Diabetic Peripheral Neuropathy Pain: A Systematic Review and Meta-Analysis.

PurposeBotulinum toxin type A (BTX-A) has been proposed as a treatment for painful diabetic peripheral neuropathy (DPN). This systematic review and meta-analysis aimed to assess the effect and safety of BTX-A for treating DPN pain.MethodsPubMed, Embase, and Cochrane Library were searched for relevant articles published up to July 7, 2021. Randomized clinical trials (RCTs) were included if they were related to the treatment of DPN pain with BTX-A. The primary outcome was the change in intensity of pain and secondary outcomes were adverse effects and changes in sleep and life quality.ResultsA total of four studies, comprising 231 patients, were included in our systematic review. BTX-A treatment induced a greater reduction in the visual analog scale score (mean difference = −2.52, 95% confidence interval [CI] [−3.06, −1.99], p < 0.001) than did the placebo treatment, with no significant heterogeneity between studies (I2 = 0). BTX-A treatment improved several neuropathy pain scale items (eg, hot sensation, sensitive sensation, unpleasant sensation, deep pain, and surface pain) significantly more than with placebo treatment (p < 0.05 for all). There was no significant difference in adverse effect (relative risk = 1.00, 95% CI [0.97, 1.03], p = 0.89).ConclusionIntradermal BTX-A injection was shown to be effective and safe in relieving DPN pain. Further larger scale and well-designed RCTs are needed.

Editorial introductions.

Editorial introductions.

Capsaicin 8% Patch for Alternative Therapy of Painful Diabetic Peripheral Neuropathy

Abstract&#x0D; Diabetes is one of the most common health problems due to its high incidence and complications. One of the complications associated with diabetes is painful diabetic peripheral neuropathy (PDPN). The capsaicin 8% patch is a localized pain treatment that provides effective pain relief from a single application in patients with peripheral neuropathic pain. The aim of this review is to discuss the effect of capsaicin patch 8% in patients with painful diabetic peripheral neuropathy. The search strategy was conducted in PubMed and modified for other databases. The search was limited to English-language reports. The keywords used were "capsaicin”, "capsaicin patch", "painful diabetic peripheral neuropathy", and "pain management". The inclusion criteria used were randomized controlled trials (RCTs), clinical trials or another interventional analysis with full text in English with publications less than the last 10 years. The exclusion criteria used were a review, systematic review, or meta-analysis, studies that were not conducted in humans and non-full text in English with publications over the last 10 years. Results: There are 2 full-text that meet inclusion criteria. From articles related to studies that have been conducted, the use of capsaicin 8% patch can reduce pain, improve nerve function and quality of life in PDPN patients. The use of capsaicin 8% patch has the advantage to pain relief for patients with painful diabetic peripheral neuropathy. &#x0D; Keywords: Alternative therapy, Capsaicin 8% Patch, Diabetes complications, Pain Relief, Painful Diabetic Peripheral Neuropathy, topical drugs

A Real-World Analysis of High-Frequency 10 kHz Spinal Cord Stimulation for the Treatment of Painful Diabetic Peripheral Neuropathy

Diabetes is one of the most prevalent chronic health conditions and diabetic neuropathy one of its most prevalent and debilitating complications. While there are treatments available for painful diabetic peripheral neuropathy (pDPN), their effectiveness is limited. This retrospective, multi-center, real-world review assessed pain relief and functional improvements for consecutive patients with diabetic neuropathy aged ≥18 years of age who were permanently implanted with a high-frequency (10 kHz) spinal cord stimulation (SCS) device. Available data were extracted from a commercial database. In total 89 patients consented to being included in the analysis. Sixty-one percent (54/89) of participants were male and the average age was 64.4 years (SD = 9.1). Most patients (78.7%, 70/89) identified pain primarily in their feet or legs bilaterally. At the last assessment, 79.5% (58/73) of patients were treatment responders, defined as having at least 50% patient-reported pain relief from baseline. The average time of follow-up was 21.8 months (range: 4.3 to 46.3 months). A majority of patients reported improvements in sleep and overall function relative to their baseline. This real-world study in typical clinical practices found 10 kHz SCS provided meaningful pain relief for a substantial proportion of patients refractory to current pDPN management, similar to published literature. This patient population has tremendous unmet needs and this study helps demonstrate the potential for 10 kHz SCS to provide an alternative pain management approach.

Quality of life in neuropathic pain: a literature review

Introduction: Neuropathic pain may develop after injury to the central nervous system, peripheral or both, when deleterious changes occur along the nociceptive modulatory pathways of the central nervous system. Proper management requires an interdisciplinary approach, as it can impact quality of life. Objectives: This review of the literature aims to assess the impact of pharmacological and non-pharmacological factors in the quality of life of patients with chronic neuropathic pain. Methodology: A systematized virtual search was carried out in PubMed®, collected articles between January 2010 and May 2020 using the terms “neuropathic pain”, “treatment”, “human” and “systematic review” using the filters of “systematic reviews ”E“ published in the last 10 years ”. All articles were formed by two independent reviewers and tabulated in a spreadsheet using Microsoft Excel® software. Results: Non-pharmacological interventions were addressed by most articles. Some articles addressed pharmacological interventions, with painful diabetic peripheral neuropathy being the main etiology. The most used quality of life measurement tools were: Medical Outcomes Study 36 (SF-36); EuroQol-5 Dimension (EQ-5D) and Beck Depression Inventory Score (BDI). Conclusion: The scarcity of high-quality studies that measure quality of life through validated tools is an obstacle to credible analysis of the impact of interventions on the life of chronic pain patients, however, in a preliminary way, cognitive behavioral therapy and the use of Spray THC/CBD oromucous has the potential to have a beneficial impact on quality of life.

Frequency Rhythmic Electrical Modulation System (FREMS) to alleviate painful diabetic peripheral neuropathy: A pilot, randomised controlled trial (The FREMSTOP study).

Frequency Rhythmic Electrical Modulated System (FREMS) is a non-invasive treatment for chronic pain conditions, but its place in the treatment algorithm for painful diabetic peripheral neuropathy (PDPN) is unknown. A pilot, open-label, randomised controlled trial in individuals with PDPN inadequately controlled on at least dual neuropathic pain treatments recruited from primary and secondary care. Participants were randomised 1:1 to FREMS+usual care (n=13) versus usual care (n=12). Primary outcome was change from baseline in perceived pain (assessed by visual analogue scale) at 12weeks between treatment groups. Of 25 participants, 14 (56%) were men, and 21 (84%) were White Europeans. Median (IQR) age and duration of diabetes were 64 (56, 68) and 14 (10, 20) years, respectively. At 12weeks, FREMS showed improvements in perceived pain compared with baseline, although the change was not statistically significant from control group (-4.0[-5.0,0.4] vs. 0[-0.3,0.7], p=0.087). There were significant improvements in pain with FREMS, assessed by McGill Pain questionnaire (p=0.042) and Douleur neuropathique-4 questionnaire (p=0.042). More participants on FREMS had greater than 30 percent reductions in perceived pain compared with controls [7/13(54%) vs 0/12(0%), p=0.042] and significant improvements in Patient Global Impression of Change (p=0.005). FREMS intervention had moderate benefits in quality of life, sleep, depression and pain medication use, but these were not statistically significant. FREMS might be used to treat individuals with PDPN inadequately controlled on two classes of neuropathic pain medications and is associated with improvements in pain severity and perceived impact of treatment. A larger, appropriately designed trial assessing its impact in this population is needed.