ArticleLiterature Review

Treating Painful Diabetic Peripheral Neuropathy: An Update

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Abstract

Painful diabetic peripheral neuropathy occurs in approximately 25% of patients with diabetes mellitus who are treated in the office setting and significantly affects quality of life. It typically causes burning pain, paresthesias, and numbness in a stocking-glove pattern that progresses proximally from the feet and hands. Clinicians should carefully consider the patient’s goals and functional status and potential adverse effects of medication when choosing a treatment for painful diabetic peripheral neuropathy. Pregabalin and duloxetine are the only medications approved by the U.S. Food and Drug Administration for treating this disorder. Based on current practice guidelines, these medications, with gabapentin and amitriptyline, should be considered for the initial treatment. Second-line therapy includes opioid-like medications (tramadol and tapentadol), venlafaxine, desvenlafaxine, and topical agents (lidocaine patches and capsaicin cream). Isosorbide dinitrate spray and transcutaneous electrical nerve stimulation may provide relief in some patients and can be considered at any point during therapy. Opioids and selective serotonin reuptake inhibitors are optional third-line medications. Acupuncture, traditional Chinese medicine, alpha lipoic acid, acetyl-l-carnitine, primrose oil, and electromagnetic field application lack high-quality evidence to support their use.

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... The most common first-line treatments for PDN are anticonvulsants, particularly pregabalin and gabapentin [8,9], despite low response rates of less than 50% [10]. Both medications have relatively high number to treat and high rates of discontinuation due to side effects [11]. ...
... Both medications have relatively high number to treat and high rates of discontinuation due to side effects [11]. Other recommended pharmacotherapies include tricyclic antidepressants and serotonin-norephinephrine reuptake inhibitors both of which have similar low efficacy [9]. ...
... Pain is rarely the only symptom of PDN; subjects frequently report numbness and paresthesias [9]. In addition to pain relief, symptoms related to neurologic sensory and reflex deficits were improved after initiation of 10 kHz SCS. ...
Article
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Aim: Previous studies of 10 kHz spinal cord stimulation demonstrated its safety and efficacy for treatment of neuropathic pain of the trunk and/or limbs. This study analyzed data from a subset of subjects with painful diabetic neuropathy enrolled in a prospective, multicenter study of peripheral polyneuropathy with various etiologies. Materials & methods: Of the eight subjects that had permanent devices, seven attended the 12-month follow-up assessment. Results & conclusion: At 12 months, 6/7 subjects were treatment responders (≥50% pain relief) and had pain remission (visual analog scale ≤ 3.0 cm). Worsening of neurologic deficits was not reported in any subject. Instead, 5/7 subjects showed improvements in sensory testing and/or reflexes. These results support further investigation of 10 kHz spinal cord stimulation as a safe and effective treatment for intractable painful diabetic neuropathy.
... Patients who experienced delirium during hospitalization were 62 times more likely to die than patients without delirium. [19] The duration of hospitalization of these patients also increases on average from 5 to 10 days. [20] Pharmacological treatments are widely used in known cases of delirium, but its effect on the outcome of the treatment has not been clearly established. ...
... [20] Pharmacological treatments are widely used in known cases of delirium, but its effect on the outcome of the treatment has not been clearly established. [19] Oxazepam, a benzodiazepine drug, is commonly used to treat the symptoms of patients who have experienced chest pain. Benzodiazepines can reduce anxiety, pain, and high cardiovascular activity. ...
Article
Background: This study aimed to compare the efficacy of gabapentin and oxazepam on sleep quality, the severity of anxiety, and pain level in patients admitted to the coronary care unit (CCU). Materials and Methods: This double-blind randomized clinical trial was done on the patients with unstable angina (UA) admitted to the CCU of Hazrat Rasool Akram Hospital in Tehran. A total of 56 patients were entered the study and randomly divided into two groups of 26. The first group was given a gabapentin capsule at a dose of 300–1200 mg/day, and the second group was given 10–20 mg of oxazepam tablets per day until hospitalization in the CCU. On the first and 4th days of hospitalization, Groningen sleep quality score (GSQS), Beck Anxiety Inventory, and severity of pain experienced by Visual Analogue Scale were recorded, and the mean frequency of chest pains was calculated in 24 h during the first 4 days. The amount of drug (morphine) prescription in CCU also compared between the two groups. Results: There was no significant difference in GSQS scores between both groups. The mean score of Beck's anxiety scale did not differ significantly between the two groups. However, the incidence of chest pain was significantly lower in the gabapentin-receiving group than in the oxazepam-receiving group (
... Currently, the only treatment to eliminate the cause of DPNP is to control blood glucose. Also, a combination of drug and non-medicinal treatments should also be used to control the symptoms of DPNP [8,9]. ...
... Because of the uncertainty of the cause of diabetic peripheral neuropathy development, curative treatments using pain relievers, Tricyclic antidepressant (TCA) are the first line of DPNP treatment and are often the only way to alleviate the discomfort and pain in these patients [9]. The most important side effect of these drugs is anticholinergic effects. ...
Article
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Background and aims: Diabetic peripheral neuropathic pain (DPNP) is one of the most common complications of diabetes and is difficult to treat. Existing treatments are often inadequate at controlling pain and limited by side-effects and drug tolerance. This study assessed the efficacy of nortriptyline versus Transcutaneous Electrical Nerve Stimulation (TENS) in patients with DPNP. Material and method: This is a randomized clinical trial study conducted on 39 patients with DPNP referring to Golestan Hospital in Ahvaz in 2017. Patients were randomly treated with TENS (18 sessions, each session 30 minutes; n=20) or nortriptyline (25 to 75 mg, once daily; n=19) for 6 weeks. Patients were evaluated for side effects and pain relief using visual analog scale (VAS). Results: There was a significant improvement in pain with both treatments compared with baseline (p˂0.001). The patients in nortriptyline group experienced more pain relief (7.21±1.51 to 0.84±1.34) than the TENS group (7.6±1.47 to 2.75 ±2.43) (P=0.001). The 50% pain relief was observed in 14 patients (73%) in nortriptyline group, 6 patients (30%) in TENS group. Moreover, the side effects were seen in 15% of TENS and 55% of patients in nortriptyline groups (P=0.019). Conclusion: Both TENS and nortriptyline were effective and safe in the management of DPNP. But nortriptyline showed a better performance on pain relief.
... The pharmacotherapies approved and used to manage PDN are mostly not traditional analgesics or opioids that can be taken "as needed" but rather agents such as anticonvulsants or antidepressants that must be taken regularly for a period of time to achieve full effect [17]. There are now more pharmacotherapies available for treating PDN than in the recent past, which are summarized in Table 2, and clinicians should consider patient-specific factors such as age, quality-of-life goals, functional status, and comorbidities when determining appropriate management [3,[18][19][20]. Information included in the table is summarized from FDA-approved package inserts and literature [21,22]. ...
... AEs reported with pregabalin treatment across many clinical studies include somnolence, dizziness, blurred vision, difficulty with concentration or attention, dry mouth, edema, and weight gain [25]. Gabapentin is another anticonvulsant frequently used to treat PDN, although it is characterized as a second-line alternative to pregabalin due to the lower quality of clinical data available for gabapentin, its less predictable pharmacokinetics, longer titration periods, less flexible dosing, and requirement for dosing adjustments in patients with renal impairments [20]. Dosing for chronic pain starts at 300 mg/day and is titrated up until suitable pain relief is achieved with effective doses ranging from 1800 mg to 3600 mg per day [27]. ...
Article
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Painful diabetic neuropathy (PDN) is a common complication of diabetes mellitus that is associated with a significant decline in quality of life. Like other painful neuropathic conditions, PDN is difficult to manage clinically, and a variety of pharmacological and non-pharmacological options are available for this condition. Recommended pharmacotherapies include anticonvulsive agents, antidepressant drugs, and topical capsaicin; and tapentadol, which combines opioid agonism and norepinephrine reuptake inhibition, has also recently been approved for use. Additionally, several neuromodulation therapies have been successfully used for pain relief in PDN, including intrathecal therapy, transcutaneous electrical nerve stimulation (TENS), and spinal cord stimulation (SCS). Recently, 10 kHz SCS has been shown to provide clinically meaningful pain relief for patients refractory to conventional medical management, with a subset of patients demonstrating improvement in neurological function. This literature review is intended to discuss the dosage and prospective data associated with pain management therapies for PDN.
... Current treatment protocols include pain relief with opioids, antidepressants, anticonvulsants and many other medications still being evaluated and investigated [7][8][9][10]. Because of limited effectiveness and known adverse effects, non-pharmacological treatment approaches like transcutaneous electrical nerve stimulation and monochromatic infrared energy therapy have been investigated [10][11][12][13][14][15]. ...
... Current treatment protocols include pain relief with opioids, antidepressants, anticonvulsants and many other medications still being evaluated and investigated [7][8][9][10]. Because of limited effectiveness and known adverse effects, non-pharmacological treatment approaches like transcutaneous electrical nerve stimulation and monochromatic infrared energy therapy have been investigated [10][11][12][13][14][15]. ...
Article
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Aim: Diabetic symmetrical peripheral neuropathy is a common complication of diabetes mellitus. Patients treated with transcutaneous CO2 application for chronic wounds reported an improvement in peripheral sensations. This study aimed to evaluate the effect of transcutaneous application of gaseous CO2 on diabetic symmetrical peripheral neuropathy. Methods: A prospective randomized, double-blind study was performed at the University Medical Center Ljubljana between September 2019 and September 2020. Sixty consecutive patients with diabetes with a unilateral chronic wound were randomized into either a study group that received transcutaneous CO2 therapy or a control group that received placebo treatment with air. Results: Vibration, monofilament sensation, and temperature of the big toe improved significantly in the study group (p < 0.001, for vibration sensation, monofilament test and temperature of the big toe), but not in the control group (p = ns for all evaluated outcomes). Conclusion: According to our results, a transcutaneous application of gaseous CO2 shows promising results in treating diabetic symmetrical peripheral neuropathy. Considering the major consequences of sensory loss leading to foot ulceration and possibly amputation, we believe this treatment approach deserves future attention and investigation as a treatment modality of diabetic symmetrical peripheral neuropathy.
... The most effective strategy to prevent complications of diabetic neuropathy is to control blood glucose [10], but medications are also available for the treatment of diabetic neuropathy [11]. The FDA approves pregabalin and Duloxetine to treat diabetic neuropathy [11], but their use may be limited by side effects and interaction with other medications [12]. ...
... The most effective strategy to prevent complications of diabetic neuropathy is to control blood glucose [10], but medications are also available for the treatment of diabetic neuropathy [11]. The FDA approves pregabalin and Duloxetine to treat diabetic neuropathy [11], but their use may be limited by side effects and interaction with other medications [12]. ...
Article
PurposeOne of the most common and debilitating complications of diabetes is peripheral neuropathy. Physical modalities such as whole-body vibration are used to treat diabetic peripheral neuropathy (DPN), but there are limted studies on the effectiveness of local vibration for the treatment of PDN. In this study, we aimed to evaluate the effectiveness of local vibration in treating a patient with DPN.Methods The local vibration was applied on the plantar side of both feet. The patient received 10 min of local vibration with 62.5 Hz frequency for five sessions. We used brief BESTest for balance evaluation, Numerical Pain Rating Scale (NPRS) for pain assessment, monofilament examination score for protective sensation evaluation, vibration threshold, and skin temperature to evaluate the effects of local vibration, which were measured before the treatment, after one session of treatment, and after 5th session of treatment.ResultsThere was a 62.5% reduction in pain severity after five sessions of treatment. Vibration threshold of both patient’s feet and protective sensation of right foot returned to normal after treatment. Skin temperature was increased in all evaluated points of both patient’s feet, brief BESTest score increased by six points after five treatment sessions, indicating improvements in the blood flow of feet and balance, respectively.Conclusions Local plantar vibration was effective in improving the symptoms of DPN.
... DPN is a well-documented complication of DM, affecting up to 50% of patients during the clinical course (Bikbova et al., 2018). It usually manifests itself late into the disease or in uncontrolled DM, with as many as 39% of patients experiencing painful DPN when left untreated (Snyder et al., 2016). An estimated 236 million persons worldwide have been diagnosed with DPN (Tesfaye and Selvarajah, 2012). ...
... Pharmaceutical agents such as tricyclic antidepressants, selective serotonin-norepinephrine reuptake inhibitors, and anticonvulsants have been used but with variable outcomes (Iqbal et al., 2018;Khdour, 2020). Analgesics such as oral or topical opioids can also be used as adjuvant treatment (Snyder et al., 2016). ...
Article
Full-text available
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.
... With results indicating that the efficacy of the capsaicin 8 % patch is comparable to that seen with other agents like pregabalin, duloxetine, gabapentin in patients with diabetic peripheral neuropathy. Recently Khdour [26], as well as Snyder and colleagues [27] reviewed literature on the first-line treatments for diabetic neuropathy such as tricyclic antidepressants, serotonin-noradrenaline reuptake inhibitors or anticonvulsants that act on calcium channels, including lidocaine patches and capsaicin cream. Further, evaluating current guidelines for the pharmacological management of diabetic peripheral neuropathy. ...
... Regarding diabetic neuropathic pain, anticonvulsants, such as pregabalin and gabapentin and antidepressants, can block the actions of serotonin and noradrenaline, currently ranks as the primary medication for pain relief [9]. While opioids are considered optional third-line medications for pain management [26,27,51], this has highlighted the need to better understand the usefulness of topical applications of lidocaine and capsaicin as adjuvants in the control of diabetic neuropathic pain [9,51]. ...
Article
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Diabetic neuropathy is a risk factor for developing complications such as autonomic cardiovascular disease, osteoarthropathy, foot ulcers, and infections, which may be the direct cause of death. Even worse, patients plagued by this condition display painful neuropathic symptoms that are usually severe and frequently lead to depression, anxiety, and sleep disarrays, eventually leading to a poor quality of life. There is a general interest in evaluating the therapeutic properties of topical capsaicin cream as an effective agent for pain relief in these patients. As such, the current review makes use of major search engines like PubMed and Google Scholar, to bring an updated analysis of clinical studies reporting on the therapeutic effects of capsaicin in patients with painful diabetic neuropathy. In fact, most of the summarized literature indicates that topical capsaicin (0.075 %) cream, when applied to the painful areas for approximately 8 weeks, can reduce pain, which may lead to clinical improvements in walking, working, and sleeping in patients with painful diabetic neuropathy. The current review also discusses essential information on capsaicin, including its source, bioavailability profile, as well as treatment doses and duration, to highlight its therapeutic potential.
... They are anticonvulsants, pregabalin, and gabapentin until the pain subsides. 6 However, this medication only addresses the manifestations of current pain, not the underlying pathophysiological causes or the sensory abnormalities shown in neuropathy studies. 5 To reduce apoptosis, oxidative stress, and neuronal inflammation, multi-target therapies are required. ...
... 5,7 Further treatment may be a possibility to help with recovery and metabolism pathology, which happens when the body's glycemic index rises, causing the hexosamine pathway to operate and induce the incidence of reactive oxygen species (ROS) and inflammatory. 6,7 Previous studies showed that Vitamin D insufficiency was common among diabetes individuals with peripheral neuropathy. Low vitamin levels are more common in females and people with chronic neuropathic. ...
Article
Full-text available
Painful neuropathic pain is a challenging chronic pain to treat. It is heterogeneous in symptoms and could be resistant to the available treatments regimen. Current pharmacological treatments fail to achieve adequate pain relief in a most patients. The previous review showed that only less than 50% of patients can achieve good pain reduction with standard adjuvant treatment. The available adjuvants analgesic only focus in the symptom control, and do not interfere with the progressing damage of the nerve. Vit D insufficiency is quite frequent in type 2 diabetes patients.diabetes, particularly those with symptoms of DPN. The studies also showed that low serum vitamin D levels are an independent predictor of DPN development. Vitamin D supplementation is necessary for diabetic neuropathy patients since it promotes the synthesis of neurotrophins and neurotransmitters. Additional vitamin D therapy have big role in nerve growth factor and the regulation of neurotrophin and Ca 2+ homeostasis in neurons, and provides protection for neurons in the peripheral nervous system. In this review, we do systematically search the studies about Vitamin D for the treatment of painful diabetic neuropathic condition. We used PubMed, Cochrane, Clinical Key, and search Google Scholar for papers that used vitamin D phrases. and painful diabetic neuropathy as our major database for this review and we make a systematic table to explain our review. However, there is still an unmet need in the management of neuropathic pain. The unmet needs maybe caused by the gap between pharmacological treatmnet in pain reduction in painful diabetic neuropathy patients. Therefore, in this review we discuss about the potential use of vitamin D as an add-on therapy to closing the gap in the management of neuropathic pain.
... In the past years, non-invasive neuromodulation (NINM) techniques have been increasingly used in the treatment of pain 8,9 . It has been showed that this neurotechnology is a feasible and safe treatment for chronic neuropathic pain 10,11 . ...
Article
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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.
... The patient presents joint lesions or ulceration in the lower extremity when the disease becomes severe, threatening the patient's limbs. [7] Clinically, mecobalamin is a commonly used drug in treating peripheral neuropathy. It can participate in the methyl transformation of substances, promote lecithin synthesis in the medullary sinus, and the metabolism of protein, nucleic acid, and lipids, repair the impaired nerve tissue, and relieve the neurological sign of patients . ...
Article
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Background: Diabetic peripheral neuropathy is a common complication of diabetes and the main cause of disability. At present, there is no specific therapeutic regimen. Mecobalamin is often used as a neurotrophic drug, and its long-term effects are not satisfactory when used alone. Clinical practice indicates that traditional Chinese medicine injection with mecobalamin has a therapeutic advantage in treating diabetic peripheral neuropathy while it lacks evidence-based medicine. In this scheme, the efficacy and safety of traditional Chinese medicine injection with mecobalamin in treating diabetic peripheral neuropathy has been studied. Methods: Computers were used to search the English database (PubMed, the Cochrane Library, Embase, Web of Science), and Chinese database (CNKI, Wanfang, CBMDISC, VIP). Besides, manual searching was conducted to search for Baidu Scholar, CHICTR, Google Scholar. During the establishment of the database to November 2020, a randomized controlled trial on traditional Chinese medicine injection with mecobalamin in treating diabetic peripheral neuropathy was conducted. There were 2 researchers independently conducting data extraction and quality evaluation of literature on the included studies, RevMan5.3 was performed for meta-analysis on the included literature. Results: In this study, the efficacy and safety of traditional Chinese medicine injection with mecobalamin in treating diabetic peripheral neuropathy was evaluated by the total effective rate, motor nerve conduction velocity, sensory nerve conduction velocity, adverse reactions, and glucose metabolism level. Conclusion: This study can provide an evidence-based basis on the clinical applications of traditional Chinese medicine injection with mecobalamin in the treatment of diabetic peripheral neuropathy. Ethics and dissemination: The study does not involve patient privacy or rights and does not require approval from an ethics committee. The results may be published in peer-reviewed journals or disseminated at relevant conferences. Osf registration number: DOI 10.17605/OSF.IO/KPW5E.
... 12 neuropathic pain conditions. 13 Though Gabapentin remains well established as a first-line treatment for diabetic neuropathy, 14,15 few randomized control studies have examined the utility of the drug in corneal neuropathic pain. 16 Ongun et al. showed a decrease in patient reported pain in a cohort of patients with chronic corneal neuropathic pain and dry eye disease treated with gabapentin compared to a placebo group. ...
Poster
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A Submillimeter Experimental Benchmark of a 67.5 MeV Proton Depth Dose Curve in Water B.A. Faddegon,1 I.K. Dafarti,1 J. Shin,2 and C.M. Castaneda3; 1University of California San Francisco, San Francisco, CA, 2St. Jude Children’s Research Hospital, Memphis, TN, 3Crocker Nuclear Laboratory, Davis, CA Purpose/Objective(s): To measure a pristine proton Bragg Peak for a 67.5 MeV proton beam with depth known to a few tenths of a millimeter and energy known with better accuracy than the depth. Materials/Methods: A time of flight (TOF) system was previously used to establish the energy of the proton beam exiting the cyclotron used for the benchmark measurement within 0.1 MeV and is also used routinely to verify the beam energy. The width of the peak was limited to 0.4 MeV FWHM based on previous CsI measurements. The beam was incident on a 101.6 um thick Ta scattering foil followed by a wire chamber, secondary electron emission monitor and 127 um thick Kapton exit window. This is minimal material of accurately known composition and density as required for measurement of the benchmark pristine Bragg Peak. The beam was collimated to a diameter of 111 mm at the exit window with a water tank oriented perpendicular to the beam axis placed 300 mm from the exit window. Radiochromic film was used to measure beam flatness, symmetry and divergence and to verify the beam axis was coincident with alignment lasers. Diodes for charged particle dosimetry from 2 different manufac- turers were centered on the beam axis with depth determined to 0.2 mm, including a discrepancy of 0.2 mm in the manufacturer specification of the sensitive volume depth in the detector. A motorized stage with 3 um reproducibility was used to step the detectors from the water tank window through the Bragg Peak. The dose rate was low enough that the measured percent depth dose curves were independent of dose rate. Parallel plate chambers with a positioning accuracy of 0.2 mm and 0.5 mm were used to verify the diode measurements. Measurement was compared to Monte Carlo simulation done with Geant4 using TOPAS. Results: The diode and parallel plate chamber depth dose curves agree within the least restrictive of the accuracy of the detector positioning and 1.5% in dose, within the repeatability of the measurement. The experi- mental benchmark for the 67.5 MeV proton beam has 0.2% accuracy in the beam energy and 0.5% accuracy in depth of the Bragg Peak. To our knowledge this accuracy exceeds that of published benchmarks. The 80% dose at the distal side of the Bragg Peak was at 37.2�0.2 mm, compared to the simulated value of 37.0 mm. The result has ramifications on the ac- curacy of the mean ionization potential needed to calculate stopping powers for the Monte Carlo simulation, with the resulting stopping power in water marginally high by 0.5�0.5%. Conclusions: The experimental benchmark met the accuracy objective. The sub-millimeter accuracy of the simulation will facilitate achieving 1-2 mm accuracy in range estimation in treatment planning for proton therapy, a worthwhile clinical goal. Author Disclosure: B.A. Faddegon: A. Employee; University of California San Francisco. E. Research Grant; NIH R01 CA140735. I.K. Dafarti: A. Employee; University of California San Francisco. J. Shin: A. Employee; St. Jude Children’s Research Hospital. C.M. Castaneda: A. Employee; Crocker Nuclear Laboratory.
... Diabetic neuropathic pain (DNP) is one of the most common complications of diabetes mellitus, affecting approximately 30%-50% of diabetes patients. [1][2][3] The main symptoms of DNP include spontaneous pain and irritation-induced pain. [4,5] Spontaneous pain can be manifested as constant burning, sharp, shooting, or even as electric shock sensations. ...
Article
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Background: Diabetic neuropathic pain (DNP) is a common complication of diabetes mellitus, it severely affects the quality of life of Diabetic patients. Acupuncture is proofed to have favorable effects in treating DNP, however, evidence needs to be gathered and interpreted. We will make a comprehensive review of clinical trials concerning acupuncture in treating DNP and do meta-analysis if possible. Method: The following databases will be searched from the inception to September 2020: PubMed, Embase, Web of Science, China National Knowledge Infrastructure, Wan-Fang Database, and Chinese Scientific Journal Database. RCTs that evaluated acupuncture for patients with DNP will be included. The primary outcome will be patient-reported pain intensity using validated scales or verbal reporting. The secondary outcomes including the Toronto clinical scoring system, Sensory Nerve Conduction Velocity, Motor Nerve Conduction Velocity, and quality of life. The study selection, data extraction, and study quality evaluation will be performed independently by 2 researchers. A meta-analysis will be performed using RevMan V5.3 statistical software if possible; otherwise, descriptive analysis or subgroup analysis will be conducted. The quality of evidence for outcomes will be assessed with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Results: This study will evaluate the effect and safety of acupuncture in treating DNP. Conclusions: The evidence we generated from the present study will provide more options for DNP management in clinical practice. Systematic review registration: INPLASY202090043.
... [4,5] Of those, pain is a constant distress. [6][7][8][9] It accounts for 10% to 30% of such population based on the different studied patients. [10][11][12][13][14][15][16][17] If it cannot be treated effectively and timely, it can significantly restrict recreational social activities, negatively impact mood, and substantially affect quality of life in patients with DPN. ...
Article
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Background: Warm needling acupuncture (WNA) has been widely utilized for pain management in patients with diabetic peripheral neuropathy (DPN). However, its results are still inconsistent, and no systematic review has specifically addressed this issue. Thus, this systematic review will comprehensively and systematically investigate the effectiveness and safety of WNA for pain relief in DPN. Methods: A comprehensive literature search of MEDLINE, EMBASE, Cochrane Library, Web of Science, Scopus, Allied and Complementary Medicine Database, CBM database, and China National Knowledge Infrastructure will be performed for randomized controlled trials that report WNA for pain relief in patients with DPN. All electronic databases will be searched from initial to the present without limitations of language and publication status. Two investigators will independently screen papers, collect data, and assess study quality. Cochrane risk of bias tool will be used for study quality assessment, and evidence quality will be evaluated using Grading of Recommendations Assessment, Development and Evaluations approach. RevMan 5.3 software will be applied for running statistical analysis. Results: This study will summarize the evidence for the effectiveness and safety of WNA for the management of pain in patients with DPN. Conclusions: The findings of this study may provide helpful evidence to judge whether WNA for pain relief in DPN is effective or not.
... 12 Table 1 outlines pharmacotherapeutic agents, including dose considerations, mechanisms, and side effects. 22,23 Anticonvulsants Pregabalin is a Food and Drug Administration (FDA)approved anticonvulsant used for the management of PDN, administered daily at 150-600 mg. Evidence shows significant pain reduction with comparable efficacy to duloxetine and gabapentin, [24][25][26][27] as well as improvements in sleep and global impression scales without affecting nerve conduction. ...
Article
The development of painful diabetic neuropathy (PDN) is a common complication of chronic diabetes that can be associated with significant disability and healthcare costs. Prompt symptom identification and aggressive glycemic control is essential in controlling the development of neuropathic complications; however, adequate pain relief remains challenging and there are considerable unmet needs in this patient population. Although guidelines have been established regarding the pharmacological management of PDN, pain control is inadequate or refractory in a high proportion of patients. Pharmacotherapy with anticonvulsants (pregabalin, gabapentin) and antidepressants (duloxetine) are common first-line agents. The use of oral opioids is associated with considerable morbidity and mortality and can also lead to opioid-induced hyperalgesia. Their use is therefore discouraged. There is an emerging role for neuromodulation treatment modalities including intrathecal drug delivery, spinal cord stimulation, and dorsal root ganglion stimulation. Furthermore, consideration of holistic alternative therapies such as yoga and acupuncture may augment a multidisciplinary treatment approach. This aim of this review is to focus on the current management strategies for the treatment of PDN, with a discussion of treatment rationale and practical considerations for their implementation.
... Diabetic neuropathic pain (DNP) is a common, troublesome diabetes complication that affects 11-21% of diabetics [2] and is associated with numbness, spontaneous pain, hyperalgesia, and allodynia [3,4]. DNP management is usually by analgesics, including pregabalin, duloxetine, and opioids [5,6], but these are not always effective. Thus, a better understanding of the mechanisms underlying DNP is needed. ...
Article
Full-text available
Diabetic neuropathic pain (DNP) is a troublesome diabetes complication all over the world. P2X3 receptor (P2X3R), a purinergic receptor from dorsal root ganglion (DRG), has important roles in neuropathic pain pathology and nociceptive sensations. Here, we investigated the involvement of DRG P2X3R and the effect of 2 Hz electroacupuncture (EA) on DNP. We monitored the rats' body weight, fasting blood glucose level, paw withdrawal thresholds, and paw withdrawal latency, and evaluated P2X3R expression in DRG. We found that P2X3R expression is upregulated on DNP, while 2 Hz EA is analgesic against DNP and suppresses P2X3R expression in DRG. To evaluate P2X3R involvement in pain modulation, we then treated the animals with A317491, a P2X3R specific antagonist, or α β-me ATP, a P2X3R agonist. We found that A317491 alleviates hyperalgesia, while α β-me ATP blocks EA's analgesic effects. Our findings indicated that 2 Hz EA alleviates DNP, possibly by suppressing P2X3R upregulation in DRG.
... This peculiar characteristic of capsaicin is the basis for its usage in relieving the pain of HIV neuropathy, post-herpetic neuralgia and surgical postoperative pain [7]. Topical capsaicin has also demonstrated moderate efficacy in diabetic peripheral neuropathy in studies conducted in Caucasians [8][9][10][11]. Despite the anatomy and physiology of a nerve being the same in all populations, pain perception and response to treatment show ethnic and racial differences with treatment response in Africans different from Caucasians [12]. Due to little available data on the long-term efficacy of topical capsaicin in the reduction of painful sensory diabetic neuropathy in sub-Saharan patients with type 2 diabetes, we sought to determine if pain relief induced by capsaicin is significant enough to be experienced by this population type. ...
Article
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Objective The aim of this study was to evaluate the efficacy of capsaicin in inducing significant pain relief in a population of sub-Saharan African type 2 diabetic patients with painful peripheral neuropathy. Design This was a prospective double-blind placebo-controlled randomised clinical trial. Setting A single tertiary-level hospital diabetes center in Yaounde, Cameroon. Participants Twenty-two participants with type 2 diabetes mellitus, presenting with painful diabetic neuropathy, aged 18 years and above. Intervention Participants were equally randomised to capsaicin or placebo. Each drug was to be applied on the lower limbs thrice daily. Follow-up was done every two weeks for eight weeks. Main outcome measure Reduction in the median pain score from baseline, as assessed by the Visual Analogue Scale. Results Twenty-two participants aged 57.5 (50-60) years with a median pain intensity of 6.8 units in the capsaicin group and 5.8 units in the placebo group were included; at inclusion, there was no significant difference in the two groups (p=0.29). After two weeks, the value of pain intensity was 3.3 [2.5-4.0] vs 5.0 [4.0-7.4] (p=0.003); at week four, 3.0 [2.5-3.3] vs 5.0 [4.2-5.5] (p=0,02); at week six, 3.3 [2.5-4.0] vs 4.8 [4.0-6.0] (p=0.03); and at week eight, 6.6 [6.0-7.0] vs 5.2 [5.0-6.0] (p=0.54) for capsaicin and placebo respectively. Conclusion This study, carried out due to a paucity of information on the effect of capsaicin and painful diabetic neuropathy in sub-Saharan African diabetes patients, shows that capsaicin significantly reduces neuropathic pain with worsening after eight weeks of use. Trial registration number Pan Africa Trial Registry: PACTR202003714748946.
... Administration of Triptolide in animal models of nerve injury has also been shown to lead to accelerated axonal regeneration and improved functional outcomes ). Together, this warranted the recent clinical explorations of Triptolide as a therapy for a number of neuropathies including diabetic neuropathy (Snyder et al. 2016). While these initial results appear promising, randomized controlled clinical trials are awaited. ...
Chapter
Peripheral neuropathies (PN) are the most common neurodegenerative disease globally. A variety of different insults lead to PN which include diabetes, cancer chemotherapy, and infectious diseases (such as HIV, Campylobacter jejuni, and hepatitis C). The clinical signs and symptoms depend on the extent of damage to motor, sensory, and autonomic fibers as well as the pain systems. Despite this heterogeneity of etiologies, the pathogenesis of PN is confined to one of several biological mechanisms that lead to eventual axonal degeneration. These molecular mechanisms allow identification of appropriate therapeutic targets to promote regeneration and functional recovery, but so far none of these preclinical discoveries resulted in clinical success. In addition, the poor ability of regenerating axons to reach their target represents a significant challenge to the development of effective regenerative therapies. This has stimulated research into new therapeutic delivery strategies. As a result, transdermal drug delivery and gene therapy have emerged as ideal candidates to circumvent these challenges. This chapter provides an insight into how these technologies can be harnessed to maximize the benefit of regenerative therapies for acquired axonal PN.
... Most of the time the clinicians treat the conditions based on the symptoms presented but today the practice of medicine is insisting more on evidence based medicine and so merely relying on the symptoms of the patients certain investigation can be made to exactly identify the peripheral neuropathy. Nerve conduction study being considered as the gold standard for diagnosing peripheral neuropathy but it is mostly used by neurologist with a sophisticated set up and presence of at least one abnormal parameter such as amplitude, latency and conduction velocity of the nerve is required for diagnosing peripheral neuropathy [4] . In the recent years High-resolution ultrasonography (HRUS) has geared up as a new diagnostic tool in the work-up of peripheral nerve diseases [5] . ...
... It is among the most common, expensive and disabling complications of diabetes, affecting approximately 30% of hospitalized patients with diabetes and 25% of patients with diabetes in the community. [401] Approximately 30% patients either with known or newly diagnosed diabetes are suffering from diabetic neuropathy. [402,403] In the cross-sectional survey of Indian patients with T2DM in CINDI and CINDI2 studies, diabetic neuropathy was prevalent in 13.15% and 13.2% patients, respectively. ...
Article
A comprehensive document cositing of Clinical practice recommendations based on teh existing vidence and consensus of all experts in teh field of diabetes throughout the country for the management of diabetes
... 12 A Cochrane review of 37 studies of 5914 patients demonstrated substantial benefit of gabapentin for reduction of chronic pain in post-herpetic neuralgia, diabetic neuropathy, and other neuropathic pain conditions. 13 Though Gabapentin remains well established as a first-line treatment for diabetic neuropathy, 14,15 few randomized control studies have examined the utility of the drug in corneal neuropathic pain. 16 18 Another study revealed that patients treated with a combination of gabapentin and pregabalin experienced decreased pain following photorefractive keratectomy (PRK). ...
Article
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Purpose To report a case of chronic neuropathic ocular pain in a patient without visual complaints. Observations A 37-year-old male with a history of bilateral laser-assisted in situ keratomileusis (LASIK) presented with pain symptoms of 8 months duration in the left eye. The prior LASIK surgery was complicated by corneal ectasia in the left eye requiring penetrating keratoplasty and subsequent placement of a glaucoma drainage implant for uncontrolled, elevated intraocular pressure. The patient was evaluated with a complete clinical examination, including Goldmann applanation tonometry, dilated fundus examination, fluorescein angiography, optical coherence tomography, and magnetic resonance imaging. After 3 weeks of treatment with gabapentin 300 mg BID, the patient reported complete resolution of the ocular pain. Conclusions and Importance: The pathophysiology of neuropathic ocular pain remains poorly understood. Clinical evaluation often reveals minimal ophthalmic exam findings, leading to an underdiagnosis of the condition by ophthalmologists. Gabapentin may be an underutilized medication in the treatment of chronic ocular pain.
... It is among the most common, expensive and disabling complications of diabetes, affecting approximately 30% of hospitalized patients with diabetes and 25% of patients with diabetes in the community. [401] Approximately 30% patients either with known or newly diagnosed diabetes are suffering from diabetic neuropathy. [402,403] In the cross-sectional survey of Indian patients with T2DM in CINDI and CINDI2 studies, diabetic neuropathy was prevalent in 13.15% and 13.2% patients, respectively. ...
... It is estimated that 25 % of diabetic patients suffer from peripheral neuropathic pain; the capsaicin creams are one of the several medications recommended for them (Snyder et al. 2016;Derry et al. 2017;Dosenovic et al. 2017). In several studies, researchers have used crude extract components present in the fruits (Tundis et al. 2011;Khan et al. 2014;Sricharoen et al. 2017). ...
Chapter
Full-text available
Capsaicinoids are a group of molecules, which impart pungency (hotness) to Capsicum fruits. The capsaicinoids are synthesized in the placenta of the Capsicum fruits. During the past few decades, there is an increasing interest in elucidation of the biosynthetic pathway of capsaicinoids. The whole genome sequencing of the highly pungent species, Capsicum chinense has revealed several important genes that are responsible for the biosynthesis of capsaicin and dihydrocapsaicin, the two major active constituents of the pungency complex, also known as capsaicinoid complex. The capsaicinoids have recently attracted a wide attention, because of its huge pharmacotherapeutic potential in treating several diseases, such as diabetes, cancer, obesity, cardiovascular, respiratory, gastric diseases and urological disorders. Further, capsaicin has been increasingly used as a molecule of choice for pain relief and many other diseases. In this chapter, we have presented briefly the sources and types of capsaicinoids, its biosynthesis, quantification of pungency and the genes responsible for its biosynthesis. Further, we have highlighted the candidate genes that are important for the biosynthesis of capsaicin and can be used for further manipulation experiments. At the end, this chapter focuses on the therapeutic potential of capsaicin in treating several diseases, such as diabetes, cancer, obesity, cardiovascular, respiratory, gastric diseases and urological disorders and its increasing role in pain relief. Finally, we have briefly discussed the mode of action of capsaicin against cancer, cardiovascular diseases, obesity management, pain relief and urological disorders.
... It is among the most common, expensive and disabling complications of diabetes, affecting approximately 30% of hospitalized patients with diabetes and 25% of patients with diabetes in the community. [401] Approximately 30% patients either with known or newly diagnosed diabetes are suffering from diabetic neuropathy. [402,403] In the cross-sectional survey of Indian patients with T2DM in CINDI and CINDI2 studies, diabetic neuropathy was prevalent in 13.15% and 13.2% patients, respectively. ...
... [3] The medications available currently provide only modest pain relief for patients who suffer from DPN. [4] The recommended first-line treatment for DPN pain includes anticonvulsants (pregabalin), serotonin-noradrenaline r e u p t a k e i n h i b i t o r s ( d u l o x e t i n e ) , a n d t r i c y c l i c antidepressants (amitriptyline). [4,5] If a patient responds poorly to these treatments, topical lidocaine and opioids may be prescribed. [6] Uncontrolled DPN pain can affect a patient's quality of life and increase the incidence of anxiety/ depression. ...
Article
Full-text available
Diabetic peripheral neuropathy (DPN) is characterized by progressive loss of peripheral nerves, which causes numbness, weakness, and severe pain. The medications available currently provide only modest relief from the pain of DPN and are associated with various side effects, which has generated an enormous demand for research on new therapeutic approaches. Dysregulation of the endocannabinoid system has been reported in DPN. Cannabinoid-based medications have gained increasing attention as a potential therapy to alleviate DPN pain. Endocannabinoids and cannabinoids' actions are mediated primarily by cannabinoid receptor 1 (CB1R) and cannabinoid receptor 2 (CB2R). Cannabinoids that activate CB1R have demonstrated a profound antinociceptive effect, although CB1R is associated with undesirable psychoactive effects. Peripherally restricted CB1R agonists help overcome this problem; however, adverse metabolic and cardiovascular effects limit its therapeutic use. In contrast, CB1R antagonists, selective CB2R agonists, and endocannabinoid metabolizing enzymes inhibitors alleviate DPN pain effectively with minimal side effects. This article provides a concise overview of the preclinical and clinical studies that have tested the therapeutic potential of targeting the endocannabinoid system to treat painful DPN.
... Capsaicin is a natural alkaloid [54]. This is thought to desensitize afferent Aδ and C fibers [55]. Two forms of capsaicin are available for the treatment of painful DSPN: a low-dose cream (0.075%) [31] and a high-dose (8%) patch (Qutenza, Acorda Therapeutics, Ardsley, NY, USA) [56]. ...
Article
Full-text available
Background and Objectives: Distal symmetrical polyneuropathy (DSPN) is one of the most common chronic complications of diabetes mellitus. Although it is usually characterized by progressive sensory loss, some patients may develop chronic pain. Assessment of DSPN is not difficult, but the biggest challenge is making the correct diagnosis and choosing the right treatment. The treatment of DSPN has three primary objectives: glycemic control, pathogenic mechanisms, and pain management. The aim of this brief narrative review is to summarize the current pharmacological treatment of painful DSPN. It also summarizes knowledge on pathogenesis-oriented therapy, which is generally overlooked in many publications and guidelines. Materials and Methods: The present review reports the relevant information available on DSPN treatment. The search was performed on PubMed, Cochrane, Semantic Scholar, Medline, Scopus, and Cochrane Library databases, including among others the terms “distal symmetrical polyneuropathy”, “neuropathic pain treatment”, “diabetic neuropathy”, “diabetes complications”, ”glycaemic control”, “antidepressants”, “opioids”, and “anticonvulsants”. Results: First-line drugs include antidepressants (selective serotonin reuptake inhibitors and tricyclic antidepressants) and pregabalin. Second- and third-line drugs include opioids and topical analgesics. While potentially effective in the treatment of neuropathic pain, opioids are not considered to be the first choice because of adverse reactions and addiction concerns. Conclusions: DSPN is a common complication in patients with diabetes, and severely affects the quality of life of these patients. Although multiple therapies are available, the guidelines and recommendations regarding the treatment of diabetic neuropathy have failed to offer a unitary consensus, which often hinders the therapeutic options in clinical practice.
... Badania przeprowadzone w grupie pacjentów z bólem o różnej etiologii wykazały skuteczność wenlafaksyny w leczeniu bólu sięgającą 72% (Gálvez et al., 2004). Potwierdzono korzyści z jej zastosowania w leczeniu polineuropatii cukrzycowej (Rowbotham et al., 2004;Snyder et al., 2016;Sumpton i Moulin, 2001) oraz polineuropatii o różnej etiologii, z wyłączeniem neuralgii pozapalnej jako powikłania zakażenia spowodowanego wirusem Herpes simplex (Dworkin et al., 2007). Zdaniem niektórych badaczy skuteczność wenlafaksyny w leczeniu bólu neuropatycznego jest porównywalna ze skutecznością amitryptyliny (Kiayias et al., 2000) oraz imipraminy (Sindrup et al., 2003). ...
Article
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Depression is sometimes referred to as the state of “mental pain” as its symptoms generate a state of generalised suffering. Mental distress is very often accompanied by physical pain. The prevalence of somatic symptoms in the population of patients with depression varies significantly depending on the study population and ranges from 30 to 95%. The incidence and severity of pain are correlated with the aging process and they tend to increase with age. The most common pain symptoms in depression include headache, back and lower back pain, pain of joints and limbs, migraine headaches and abdominal pain. The pain may sometimes mask depression by coming to the fore in the clinical picture and making it difficult to establish an accurate diagnosis. The fact that antidepressants are effective in chronic pain syndromes, while not all antidepressants show the same analgesic efficacy, is the direct evidence for the common pathogenetic mechanisms of chronic pain and depression. Tricyclic antidepressants were the first antidepressants to be used in the treatment of pain symptoms in various disease states. Numerous studies have confirmed the analgesic efficacy of serotonin and noradrenaline reuptake inhibitors, which are characterised by a much better tolerance and a more favourable safety profile compared to tricyclic antidepressants; however, their analgesic effect is clearly marked only at doses that, in addition to the effect on serotonergic transmission, also affect the noradrenergic transmission. The article summarises the scientific evidence for the purposefulness of the use of venlafaxine in the treatment of chronic pain, in particular pain syndromes associated with depression, and presents two clinical cases with a commentary.
... The only treatments for PDN that are approved by the US Food and Drug Administration (FDA) are pregabalin, duloxetine, and tapentadol extended-release. Gabapentin is also commonly prescribed, as are tricyclic antidepressants, opioid analgesics, topical lidocaine, capsaicin cream, isosorbide dinitrate spray, and transcutaneous electrical nerve stimulation [4]. These treatments demonstrate various degrees of success, and many times initial treatments are discontinued, indicating low levels of satisfaction or poor tolerability [5]. ...
Article
Full-text available
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 alternative therapy for treatment of painful diabetic neuropathy of the lower extremities. We performed a systematic literature review to evaluate the safety and effectiveness of this procedure. A literature search identified 14 prospective studies. Based on our analysis of the available evidence, there is moderate-quality evidence for the safety and efficacy of spinal cord stimulation for painful diabetic neuropathy. However, further high-quality research, including a large-scale randomized controlled trial is warranted.
... Second-line and third-line therapies include opioidlike medications (tramadol and tapentadol), venlafaxine, desvenlafaxine, and topical agents (lidocaine patches and capsaicin cream). 77 Lidocaine patch may be an useful therapy for the treatment of pain relief in DPN. 78 One of the advantages of topical lidocaine is that it avoids the systemic route of drug metabolism compared to 79,80 The oral route exhibits a variety of potential AEs, especially in vulnerable patients and older patients with comorbidities and polypharmacy. ...
Article
Full-text available
Topical lidocaine is widely used in current practice for a variety of pain conditions. This literature review shows that its limited absorption and relative lack of systemic adverse events are an attractive analgesic option for a number of vulnerable patients. Topical lidocaine has been approved by health authorities for the treatment of post-herpetic neuralgia in a number of countries, and studies present some degree of evidence of its efficacy and safety in postsurgical pain, diabetic peripheral neuropathy, carpal tunnel syndrome, chronic lower back pain and osteoarthritis. Topical lidocaine may be a great alternative alone or in addition to systemic drugs and non-pharmacological approaches for an optimized pain management and in multimodal analgesia.
... 9 Clinically, DPN is manifested by numbness, paresthesias and burning pain that proximally progresses across feet and hand in a stocking-glove distribution. 10 The pathogenesis of DPN is quite complex. Suggested pathogenic mechanisms include mitochondrial dysfunction 11 and Schwann cells apoptosis 12 induced by hyperglycemia, dyslipidemia, insulin resistance, oxidative stress and the chronic inflammatory state related to DM. 13 In spite of the marked progress achieved in management of DPN, the efficacy of available treatment options is far from optimal, and no disease-modifying drug exists. ...
Article
Background and aim: Diabetic peripheral neuropathy (DPN) is one of the most common and disabling complications of DM. Many studies documented the prevalence of clinical and subclinical hypothyroidism (SCH) in diabetic patients but not in the particular group of patients with DPN. The present study aimed to determine the prevalence of SCH in DPN patients and to evaluate its association with severity of DPN. Patients and methods: The present cross-sectional study was conducted on 300 consecutive patients with DPN. The clinical manifestations of DPN were documented according to the validated Arabic version of the Michigan Neuropathy Screening Instrument. Severity of DPN was categorized into mild (6-8 points), moderate (9-11 points) or severe (12+ points) according to the Toronto Clinical Scoring System. All patients were submitted to careful history-taking and full clinical and neurological examination. Patients were diagnosed with SCH if they had TSH level above the upper limit of the normal reference range in association with normal free thyroxine (FT4) level. Results: SCH was prevalent in 53 patients (17.7%, 95% CI: 13.5%-22.5%). Patients with SCH had significantly higher frequency of severe DPN (52.8% versus 28.3%, p=0.003). It was also shown that patients with SCH had significantly higher HbA1c (8.4 ± 1.0 versus 7.3 ± 1.2%, p<0.001) and HOMA-IR (3.7 ± 0.8 versus 2.7 ± 0.9, p<0.001) when compared with patients without SCH. Logistic regression analysis identified patients' age [OR (95% CI): 1.06 (1.03-1.08), p<0.001], HbA1c [OR (95% CI): 2.2 (1.7-2.9), p<0.001] and SCH [OR (95% CI): 7.7 (3.6-15.5), p<0.001] as independent predictors of DPN severity. Conclusion: The present study showed that SCH is highly prevalent in DPN patients and is independently related to its severity.
... There are numerous studies about the involvement of chemerin in diabetic complications (22)(23)(24)(25)(26)(27) and the effects of α-LA in diabetic neuropathy (24,(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47) and DN (48)(49)(50), but to our knowledge, there have been no previous studies that investigated the effect of α-LA in chemerin-induced human mesangial cell injury and the underlying mechanisms. The purpose of this study was to explore the relationship between chemerin and P38 MAPK in the development of DN using HMCs and to examine the effects of α-LA on inflammatory cytokines. ...
Article
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Objectives: Chemerin is associated with insulin resistance, obesity, and metabolic syndrome. α-lipoic acid (α-LA) is a potent antioxidant involved in the reduction of diabetic symptoms. This study aimed to investigate the relationship between chemerin and P38 MAPK in the progression of diabetic nephropathy (DN) and examine the effects of α-LA on chemerin-treated human mesangial cells (HMCs). Materials and methods: HMCs were transfected with a chemerin-overexpressing plasmid. HMCs were also treated with high-glucose, chemerin, α-LA, PDTC (pyrrolidine dithiocarbamate ammonium, NF-κB p65 inhibitor), and/or SB203580 (P38 MAPK inhibitor). Cell proliferation was tested using the Cell Counting Kit-8 assay. Collagen type IV and laminin were tested by ELISA. Chemerin expression was detected by qRT-PCR. The chemerin receptor was detected by immunohistochemistry. Interleukin-6 (IL-6), tumor necrosis factor-a (TNF-α), nuclear factor-κBp-p65 (NF-κB p-p65), transforming growth factor-β (TGF-β), and p-P38 mitogen-activated protein kinase (p-P38 MAPK) were evaluated by western blot. Results: High-glucose culture increased the expression of the chemerin receptor. α-LA inhibited HMC proliferation. Chemerin overexpression increased collagen type IV and laminin expression. P38 MAPK signaling was activated by chemerin, resulting in up-regulation of IL-6, TNF-α, NF-κB p-p65, and TGF-β. SB203580, PDTC, and α-LA reversed the effects of chemerin, reducing IL-6, TNF-α, NF-κB p-p65, and TGF-β expression. Conclusion: Chemerin might be involved in the occurrence and development of DN. α-LA might prevent the effects of chemerin on the progression of DN, possibly via the P38 MAPK pathway.
... 9 Clinically, DPN is manifested by numbness, paresthesias and burning pain that proximally progresses across feet and hand in a stocking-glove distribution. 10 The pathogenesis of DPN is quite complex. Suggested pathogenic mechanisms include mitochondrial dysfunction 11 and Schwann cells apoptosis 12 induced by hyperglycemia, dyslipidemia, insulin resistance, oxidative stress and the chronic inflammatory state related to DM. 13 In spite of the marked progress achieved in management of DPN, the efficacy of available treatment options is far from optimal, and no disease-modifying drug exists. ...
Article
Full-text available
Background and Aim: Diabetic peripheral neuropathy (DPN) is one of the most common and disabling complications of DM. Many studies documented the prevalence of clinical and subclinical hypothyroidism (SCH) in diabetic patients but not in the particular group of patients with DPN. The present study aimed to determine the prevalence of SCH in DPN patients and to evaluate its association with severity of DPN. Patients and Methods: The present cross-sectional study was conducted on 300 consecutive patients with DPN. The clinical manifestations of DPN were documented according to the validated Arabic version of the Michigan Neuropathy Screening Instrument. Severity of DPN was categorized into mild (6– 8 points), moderate (9– 11 points) or severe (12+ points) according to the Toronto Clinical Scoring System. All patients were submitted to careful history-taking and full clinical and neurological examination. Patients were diagnosed with SCH if they had TSH level above the upper limit of the normal reference range in association with normal free thyroxine (FT4) level. Results: SCH was prevalent in 53 patients (17.7%, 95% CI: 13.5%– 22.5%). Patients with SCH had significantly higher frequency of severe DPN (52.8% versus 28.3%, p=0.003). It was also shown that patients with SCH had significantly higher HbA1c (8.4 ± 1.0 versus 7.3 ± 1.2%, p< 0.001) and HOMA-IR (3.7 ± 0.8 versus 2.7 ± 0.9, p< 0.001) when compared with patients without SCH. Logistic regression analysis identified patients’ age [OR (95% CI): 1.06 (1.03– 1.08), p< 0.001], HbA1c [OR (95% CI): 2.2 (1.7– 2.9), p< 0.001] and SCH [OR (95% CI): 7.7 (3.6– 15.5), p< 0.001] as independent predictors of DPN severity. Conclusion: The present study showed that SCH is highly prevalent in DPN patients and is independently related to its severity. Keywords: diabetes mellitus, diabetic peripheral neuropathy, subclinical hypothyroidism, thyroid hormones, thyroid dysfunction
... However, systematic studies of the involvement of other P2X receptors in DNP are lacking. DNP is usually managed by using analgesics, like duloxetine, pregabalin, and opioids [19,20], but these are not always effective and have significant side effects. Clinically, electroacupuncture (EA) is employed to treat various chronic pain disorders [21][22][23][24] and has potential use in DNP treatment [25]. ...
Article
Full-text available
Diabetic neuropathic pain (DNP) is highly common in diabetes patients. P2X receptors play critical roles in pain sensitization. We previously showed that elevated P2X3 expression in dorsal root ganglion (DRG) contributes to DNP. However, the role of other P2X receptors in DNP is unclear. Here, we established the DNP model using a single high-dose streptozotocin (STZ) injection and investigated the expression of P2X genes in the DRG. Our data revealed elevated P2X2, P2X4, and P2X7 mRNA levels in DRG of DNP rats. The protein levels of P2X4 and P2X7 in DNP rats increased, but the P2X2 did not change significantly. To study the role of P2X4 and P2X7 in diabetes-induced hyperalgesia, we treated the DNP rats with TNP-ATP (2’,3’-O-(2,4,6-trinitrophenyl)-adenosine 5’-triphosphate), a nonspecific P2X1–7 antagonist, and found that TNP-ATP alleviated thermal hyperalgesia in DNP rats. 2 Hz electroacupuncture is analgesic against DNP and could downregulate P2X4 and P2X7 expression in DRG. Our findings indicate that P2X4 and P2X7 in L4–L6 DRGs contribute to diabetes-induced hyperalgesia, and that EA reduces thermal hyperalgesia and the expression of P2X4 and P2X7.
... Overall, the diversity of mechanisms determines that PDPN is difficult to cure. Current first-line treatment for PDPN is nonspecific, and serious adverse effects limit their clinical use (Todorovic, 2015;Snyder et al., 2016). Hence, deeper knowledge in molecular and cellular mechanisms of PDPN is urgently needed to provide a basis for pharmaceutical development. ...
Article
Full-text available
Mechanical allodynia (MA) is the main reason that patients with diabetic peripheral neuropathy (DPN) seek medical advice. It severely debilitates the quality of life. Investigating hyperglycemia-induced changes in neural transcription could provide fundamental insights into the complex pathogenesis of painful DPN (PDPN). Gene expression profiles of physiological dorsal root ganglia (DRG) have been studied. However, the transcriptomic changes in DRG neurons in PDPN remain largely unexplored. In this study, by single-cell RNA sequencing on dissociated rat DRG, we identified five physiological neuron types and a novel neuron type MAAC (Fxyd7+/Atp1b1+) in PDPN. The novel neuron type originated from peptidergic neuron cluster and was characterized by highly expressing genes related to neurofilament and cytoskeleton. Based on the inferred gene regulatory networks, we found that activated transcription factors Hobx7 and Larp1 in MAAC could enhance Atp1b1 expression. Moreover, we constructed the cellular communication network of MAAC and revealed its receptor-ligand pairs for transmitting signals with other cells. Our molecular investigation at single-cell resolution advances the understanding of the dynamic peripheral neuron changes and underlying molecular mechanisms during the development of PDPN.
... Several other anticonvulsants, antidepressants and analgesics have been studied for DPN with varying results. 48 For people who do not obtain adequate relief from a first-line agent, consideration can be given to tapentadol, which does possess an FDA indication for DPN, or tramadol. 18 The ADA endorses tapentadol as an alternative in people who do not achieve pain control with first-line options, although its clinical efficacy is questionable, and data appear to be conflicting on its therapeutic benefit. ...
Article
Diabetic peripheral neuropathy (DPN) is a major complication of diabetes mellitus. Tight glycaemic management focused on lowering haemoglobin A1C and increasing time in the target glucose range along with metabolic risk factor management form the cornerstone of DPN prevention. However, there is limited evidence supporting the efficacy of glycaemic and metabolic control in reducing the symptoms and complications of DPN, including pain once painful DPN develops. DPN treatments include pharmacological agents and non-pharmacological interventions such as foot care and lifestyle modifications. Pharmacological agents primarily address pain symptoms, which affect 25-35% of people with DPN. First-line agents include the anticonvulsants pregabalin and gabapentin, the serotonin-norepinephrine reuptake inhibitors duloxetine and venlafaxine, and secondary amine tricyclic antidepressants, including nortriptyline and desipramine. All agents have unique pharmacological, safety and clinical profiles, and agent selection should be guided by the presence of comorbidities, potential for adverse effects, drug interactions and costs. Even with the current treatment options, people are commonly prescribed less than the recommended dose of medications, leading to poor management of DPN symptoms and treatment discontinuation. By keeping up with the latest therapy algorithms and treatment options, healthcare professionals can improve the care for people with DPN.
... Administration of Triptolide in animal models of nerve injury has also been shown to lead to accelerated axonal regeneration and improved functional outcomes ). Together, this warranted the recent clinical explorations of Triptolide as a therapy for a number of neuropathies including diabetic neuropathy (Snyder et al. 2016). While these initial results appear promising, randomized controlled clinical trials are awaited. ...
Article
Neuropathic pain is common in the geriatric population. Diagnosis requires a thorough history and physical examination to differentiate it from other types of pain. Once diagnosed, further workup is required to elucidate the cause, including potential reversible causes of neuropathy. When treating neuropathic pain in the elderly, it is important to consider patients' comorbidities and other medications to avoid drug-drug interactions and iatrogenic effects given the physiologic changes of drug metabolism in the elderly. Nonsystemic therapies and topical medications should be considered. Systemic medications should be started at low dose and titrated up slowly with frequent monitoring for adverse effects.
Article
Introduction: Antioxidants may have positive impact on diabetic polyneuropathy (DPN), presumably due to alleviation of oxidative stress. We aimed to evaluate the efficacy and safety of combination of antioxidants: succinic acid, inosine, nicotinamide, and riboflavin (SINR) in the treatment of DPN. Research design and methods: In a double-blind, placebo-controlled clinical trial, men and women aged 45-74 years with type 2 diabetes and symptomatic DPN, with initial Total Symptom Score (TSS) ˃5, were randomized into experimental (n=109) or placebo (n=107) group. Patients received study medication/placebo intravenously for 10 days, followed by oral administration for 75 days. Statistical significance was defined as a two-tailed p<0.05. Results: In SINR group, mean TSS change after 12 weeks was -2.65 (±1.46) vs -1.73 (±1.51) in the placebo group (p<0.0001; t-test). Reduction of symptoms in the SINR group was achieved regardless of hemoglobin A1c levels, but better results were observed in patients with initial TSS <7.5. The analysis of TSS subscores revealed statistically significant between-group differences by dynamics of the intensity of paresthesia and of numbness starting from day 11 (p=0.035 and p=0.001, respectively; mixed model); by day 57, statistically significant between-group differences were detected also by dynamics of burning intensity (p=0.005; mixed model). Study limitations are small effect size, moderate proportion of patients with severe DPN symptoms, subjective assessment of outcomes, exclusion of participants who received injectable glucose-lowering medications other than insulins, and patients with uncontrolled and type 1 diabetes. Conclusions: The combination of SINR effectively alleviates DPN symptoms in patients with type 2 diabetes. Trial registration number: ClinicalTrials.gov Registry (NCT04649203; Unique Protocol ID: CTF-III-DM-2019).
Article
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Neuropathic pain is a frequent condition caused by a lesion or disease of the central or peripheral somatosensory nervous system. A frequent cause of peripheral neuropathic pain is diabetic neuropathy. Its complex pathophysiology is not yet fully elucidated, which contributes to underassessment and undertreatment. A mechanism-based treatment of painful diabetic neuropathy is challenging but phenotype-based stratification might be a way to develop individualized therapeutic concepts. Our goal is to review current knowledge of the pathophysiology of peripheral neuropathic pain, particularly painful diabetic neuropathy. We discuss state-of-the-art clinical assessment, validity of diagnostic and screening tools, and recommendations for the management of diabetic neuropathic pain including approaches towards personalized pain management. We also propose a research agenda for translational research including patient stratification for clinical trials and improved preclinical models in relation to current knowledge of underlying mechanisms.
Article
Background: About 75% of patients with cerebral infarction suffer from sensory impairment in varying degrees. It prolongs the time for patients to resume normal life and work. The aim of this study was to retrospectively investigate the clinical characteristics affecting the recovery of sensory impairment. Materials and methods: This was a retrospective case-control study. Data of inpatients at the First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine were investigated. We collected information on the patients with sensory disturbances after cerebral infarction. Cases were defined according to whether the National Institutes of Health Stroke Scale (NIHSS) and visual analogue scale (VAS) scores improved. A total of 1078 inpatients from January 1, 2019, to December 31, 2021, were screened. Among those, 187 cases included in this study were divided into no improvement and improvement groups. We compared the clinical characteristics affecting the rehabilitation of these patients. Results: The number of patients aged between 63 and 73 years in the no improvement group were significantly higher (P<0.05). The incidence of coronary heart disease and thalamus infarction was significantly higher in patients in the no improvement cohort (P<0.05). Furthermore, coronary heart disease [odds ratio=0.466, 95% confidence interval (0.252, 0.863), P=0.015] and thalamic infarction [odds ratio=0.457, 95% confidence interval (0.230, 0.908), P=0.025] were the independent risk factors against the recovery of sensory disturbance after cerebral infarction. Conclusions: Patients with thalamus infarction and coronary heart disease may be more inclined to recover poorly from somatosensory deficits.
Article
Painful diabetic peripheral neuropathy is characterized by burning, stabbing, or electric shock–type pain, which severely impacts day‐to‐day functioning and quality of life. Here, we report the results of 3 phase I studies with NRD135S.E1 (referred to as NRD.E1), a new, orally available chemical entity, presently developed for the treatment of painful diabetic peripheral neuropathy. The first study was a first‐in‐human, randomized, placebo‐controlled, single‐ascending‐dose study, where NRD.E1 was administered to healthy male subjects in single dosages ranging from 300 to 1200 mg. The second study was a randomized, placebo‐controlled multiple‐dose study, where healthy male subjects received 300 mg of NRD.E1 once daily for 5 consecutive days. The third study was an open‐label food interaction study in healthy men and women following a crossover design, where NRD.E1 was administered under fed and fasted conditions at 40 mg. The studies revealed dose‐dependent absorption, increased exposure to NRD.E1 when administered with food, and no relevant accumulation after once‐daily administration. All 3 phase I studies consistently showed rapid absorption of orally administered NRD.E1 followed by fast elimination, mainly via metabolization (glucuronidation), and small secondary increases in plasma concentrations. NRD.E1 was well tolerated, with no subject discontinuation due to treatment‐emergent adverse events in any study.
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To effectively care for patients who are at risk of opioid-related mortality and morbidity, clinical pharmacists must consider the following: • People who inject opioids are at extremely high risk of mortality and morbidity, and identification of their use should result in expanded care delivery rather than punitive action. • Supply reduction interventions that decrease the availability of prescription opioids for misuse result in increased use of more dangerous illegal substances; thus, they should be paired with harm reduction interventions to maximize public health benefit. • Opioid intoxication may lead to fatal poisoning by inducing severe respiratory depression and hypoxia. Risk of overdose increases over time and with escalating doses. • Naloxone is a potent opioid antagonist that can rapidly reverse opioid-induced respiratory depression. Many formulations of naloxone are available for layperson administration. None of these formulations has been proven more effective than another. • The evidence base supporting expanded access to naloxone through pharmacies, primary care clinics, hospitals, and community organizations is substantial. Pharmacists can play a key role in overdose prevention across all of these settings. • Syringe services programs are endorsed by the CDC for prevention of injection-related infections and associated morbidity, however they remain illegal in 15 states. Effective pharmacy-based syringe access can fill this gap. • Fentanyl cannot cause an overdose through passive exposure, and it is not resistant to naloxone. However, it is extremely potent and increasingly found in the illegal drug supply. Fentanyl test strips can help patients identify it and modify their drug use behaviors. • Typical naloxone doses can effectively reverse the effects of fentanyl and fentanyl analogs. However, naloxone may need to be administered more quickly in the case of a fentanyl overdose, given the rapid onset of effect.
Article
Diabetes mellitus remains a public health problem, affecting 422 million people worldwide. Currently, there is no consensus around treating painful diabetic peripheral neuropathy in a step-wise manner. Among the non-pharmacological interventions, neuromodulation has become a promising alternative. Over the past decade, significant clinical trials have paved the way for prompt inclusion of high-frequency spinal cord stimulation within the painful diabetic peripheral neuropathy treatment algorithm. This article aims to provide an updated evidence-based approach for the management of painful diabetic peripheral neuropathy.
Article
Diabetes is a chronic metabolic disease characterized by an excess of glucose in the blood. If the constant sugar level is not managed correctly in diabetic patients, it may lead to microvascular complications such as diabetic retinopathy, neuropathy, and nephropathy. There are several synthetic drugs for the management of diabetes; however, these drugs produce immense adverse effects in long-term use. Flavonoids are naturally occurring substances categorized in various classes. They are known for their diverse pharmacological actions, and one of them is prominent antihyperglycemic action and their activities in diabetic complications. In the last few decades, many research studies emphasized the potential of flavonoids in diabetes management. Nevertheless, most flavonoids are insoluble in water and cannot produce desired therapeutic action when administered in conventional dosage forms. To overcome this issue, flavonoids were formulated into different nanoformulations to enhance solubility, absorption, and therapeutic efficacy. This review article focuses on flavonoid nanoformulations and in vitro and in vivo studies reported to overcome diabetes mellitus and its complications.
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Diabetic polyneuropathy (DPN) is the most common complication associated with morbidity, mortality, and healthcare costs. As approximately 50% of diabetic mellitus patients are estimated to develop peripheral neuropathy, management and treatment programs for DPN are of global concern. Prolonged exposure to hyperglycemia can damage peripheral nerves, thereby causing DPN. Management of painful DPN has targeted various pathogenetic mechanisms of diabetic polyneuropathies. Due to our growing understanding of the association between metabolic syndrome and DPN, DPN pain management now places more emphasis on pathophysiological aberrations. Intensive glycemic control can prevent DPN in patients with type 1, but not type 2 diabetes. The range of medicines that are effective for treating painful DPN include anticonvulsants, tricyclic antidepressants, serotonin norepinephrine reuptake inhibitors, and opioid analgesia. Although recent developments in examination and diagnostic criteria have made it possible to detect DPN at an earlier stage and start aggressive intervention, further research into better treatments for DPN are necessary, as there are still limitations for the present treatments of painful DPN.
Article
AimsDiabetic peripheral neuropathy affects up to 60% of individuals and often leads to foot ulceration and eventual amputation. When oral therapy has failed to achieve pain relief, the first line local treatment is the 5% lidocaine-medicated plaster which provides local relief. Capsaicin 8% patch is considered a promising topical treatment for diabetic peripheral neuropathy. The present study investigated the efficacy, safety and tolerability of capsaicin 8% patch vs 5% lidocaine patch treatments over 24 weeks in South Asian male diabetic patients with established peripheral diabetic neuropathy.Methods Analgesic effectiveness was assessed by observing any change in the Numeric Pain Rating Scale (NPRS) score, Brief Pain Inventory (BPI) for painful diabetic peripheral neuropathy (BPI-DPN question 4) and Patient Global Impression of Change (PGIC). All patients received 4% lidocaine gel/cream for 60 min prior to patch application. The trial was probably underpowered, taking into account the smaller than expected number of participants from the calculated 350 sample size required for the whole study. Two hundred ninety-one individuals were divided into three groups based on treatment regimen; Group LL (Lidocaine + Lidocaine), Group LP (Lidocaine + Placebo), Group LC (Lidocaine + Capsaicin). The treatment procedure was conducted once initially and then repeated once at 12 weeks. The patients were followed up on alternate weeks till 24 weeks after the initial treatment.ResultsGroup LC experienced a more significant reduction in the average pain intensity (p < 0.05) during the last twenty-four hours. Group LC showed more significant reduction of pain compared to control (p < 0.01), a baseline score of 5.4 ± 1.2 dropped to 3.2 ± 1.5 by week 24 of treatment. The change in mean daily pain intensity was – 2.2 ± 1.5 [95% CI: −2.45, −1.5]. Group LL and LC experienced a significant overall improvement (slightly, much or very much) in the health status during the study. After the second week of the treatment, patient satisfaction scores were 2.1 ± 1.1 in Group LL which increased to 3.2 ± 1.2 by week 24 of treatment. The capsaicin 8% patch appears to be reasonably well tolerated since there were no discontinuations because of serious drug-related treatment emergent adverse event (TEAEs).Conclusions The aim of the present study was to assess the efficacy, safety and tolerability of the 8% capsaicin patch in patients with established painful diabetic neuropathy. There was a sustained treatment response to the initial and repeat treatment of the capsaicin 8% patch over the 24 weeks. The study population was very specific so further studies are required to investigate the generalizability of the results for patients experiencing painful diabetic neuropathy. The patch could be considered as an effective long-term treatment option in individuals with painful diabetic neuropathy, particularly those experiencing inadequate pain relief or side effects from systemic therapies.
Article
Diabetes has been the largest global epidemic in 21st century, and the cost for diabetes and its complications is about 12% of global health expenditure. Diabetic neuropathy is the most common complication of diabetes, affecting up to 50% of patients over the course of their disease. Among them, 30‐50% develop neuropathic pain, which has typical symptoms that originate from toes and progress to foot ulcer and seriously influences the quality of life. The pathogenesis of diabetic neuropathic pain (DNP) is complicated and incompletely understood and there is no effective treatment except supportive treatment. Long non‐coding RNAs (lncRNAs), a class of non‐coding RNAs exceeding 200 nucleotides in length, have been shown to play key roles in fundamental cellular processes, which are considered to be potential targets for treatment. Recent researches indicate that lncRNA is involved in the pathogenesis of DNP. Certain over‐expressed lncRNAs can enhance the purinergic receptor‐mediated neuropathic pain in peripheral ganglia and inflammatory cytokines are released due to receptors activated by ATP. In recent years, our laboratory also has been exploring the relationship and pathogenesis between lncRNAs and DNP. In this review, we put stress on the recent progress of functional lncRNAs associated with DNP and investigate their roles related to respective receptors. This article is protected by copyright. All rights reserved.
Article
Background Neuropathies, the most common complication of diabetes, manifest in various forms, including entrapments, mononeuropathies or, most frequently, a distal symmetric polyneuropathy. Painful diabetic neuropathy (PDN) in the classic “stocking” distribution is a disease of increasing prevalence worldwide and a condition for which standard medical treatment only provides modest relief. Neuromodulation offers a potential alternative to pharmacotherapies given its demonstrated efficacy in other refractory chronic neuropathic pain syndromes. High-quality evidence from randomized controlled trials (RCTs) is available in these other settings for two approaches to spinal cord stimulation (SCS): (1) conventional low-frequency SCS (LF-SCS), which modulates axonal activity in the dorsal column and is paresthesia-dependent, and (2) high-frequency SCS delivered at 10 kilohertz (10 kHz SCS), which targets neurons in the superficial dorsal horn and is paresthesia-independent. Method This review examines the evidence for SCS from published RCTs as well as prospective studies exploring the safety and effectiveness of treating PDN with neuromodulation. Results Two RCTs enrolling 60 and 36 participants with PDN showed treatment with LF-SCS reduced daytime pain by 45% to 55% for up to two years. An RCT testing 10 kHz SCS versus conventional medical management (CMM) in 216 participants with PDN revealed 76% mean pain relief after six months of stimulation. None of the studies revealed unexpected safety issues in the use of neuromodulation in this patient population. Conclusion These well-designed RCTs address the unmet need for improved PDN therapies and provide data on the safety, effectiveness, and durability of SCS therapy.
Article
Patients with diabetes mellitus may experience painful and nonpainful diabetic peripheral neuropathy (DPN). This article offers an overview of DPN and the clinical assessment and management of patients with DPN, as well as the nurse's role in supporting these patients.
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This guideline provides recommendations for primary care clinicians who are prescribing opioids for chronic pain outside of active cancer treatment, palliative care, and end-of-life care. The guideline addresses 1) when to initiate or continue opioids for chronic pain; 2) opioid selection, dosage, duration, follow-up, and discontinuation; and 3) assessing risk and addressing harms of opioid use. CDC developed the guideline using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework, and recommendations are made on the basis of a systematic review of the scientific evidence while considering benefits and harms, values and preferences, and resource allocation. CDC obtained input from experts, stakeholders, the public, peer reviewers, and a federally chartered advisory committee. It is important that patients receive appropriate pain treatment with careful consideration of the benefits and risks of treatment options. This guideline is intended to improve communication between clinicians and patients about the risks and benefits of opioid therapy for chronic pain, improve the safety and effectiveness of pain treatment, and reduce the risks associated with long-term opioid therapy, including opioid use disorder, overdose, and death. CDC has provided a checklist for prescribing opioids for chronic pain (http://stacks.cdc.gov/view/cdc/38025) as well as a website (http://www.cdc.gov/drugoverdose/prescribingresources.html) with additional tools to guide clinicians in implementing the recommendations.