scholarly journals Phenotyping animal models of diabetic peripheral neuropathy in rats: advantages and limitations

2018 ◽  
Vol 64 (3) ◽  
pp. 188-193
Author(s):  
Zera N. Abdulvapova ◽  
Ekaterina V. Artemova ◽  
Anna M. Gorbacheva ◽  
Gagik R. Galstyan ◽  
Alla Yu. Tokmakova ◽  
...  

Diabetic polyneuropathy is one of the most common late complications of diabetes mellitus, as well as the main cause of ulcerative foot defects. The prevalence of neuropathy among people with diabetes varies from 28 to 65%, depending on the disease duration and diagnostic features. Initial signs of damage are detected as early as in prediabetes. To date, there is a fairly limited knowledge of the mechanisms of nerve fiber damage in diabetes. Also, it is unclear which type of nerve fibers is involved in damage first and how the nervous system regulates repair of tissues and local immunity. Animal models of diabetic peripheral neuropathy enable studying new aspects of the pathogenesis of this common diabetes complication and open prospects for the search and development of new drugs.

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Francesca Magrinelli ◽  
Chiara Briani ◽  
Marcello Romano ◽  
Susanna Ruggero ◽  
Elisabetta Toffanin ◽  
...  

Diabetic peripheral neuropathy (DPN) is a frequent complication of type 2 diabetes mellitus (DM) and may involve small and large peripheral nerve fibers. Recent evidence suggests a role of cytokines in DPN. The paper is aimed at exploring whether the serum concentration of cytokines is associated with small and large nerve fiber function and with neuropathic pain (NP). We recruited a group of 32 type 2 DM patients who underwent serum cytokines (TNF-α, IL-2, IL-4, IL-6, and IL-10) dosage as well as electrodiagnostic and quantitative sensory testing (QST) assessment to explore damage to large and small nerve fibers. Raised serum levels of IL-6 and IL-10 correlated with markers of large nerve fiber sensory and motor axonal damage. Raised IL-10 serum level was associated with signs of motor nerve demyelination. No differences were found in pain characteristics and electrodiagnostic and QST markers of small nerve fiber function in relation to cytokines serum levels. IL-6 and IL-10 serum levels were associated with large nerve fiber damage but not to small fibers function or NP. IL-6 and IL-10 cytokines might play a role in the pathogenesis of nerve fiber damage or represent a compensatory or neuroprotective mechanism.


2020 ◽  
Vol 4 (1) ◽  
pp. 46-51
Author(s):  
Leny Candra Kurniawan ◽  
Ikhwan Abdullah

Diabetic Peripheral Neuropathy is a type of nerve damagethat occurs due to diabetes. High blood sugar levels in thelong term can cause damage to nerve fibers throughout thebody, such as legs, feet, blood circulation, heart, digestivesystem, and urinary tract. Diabetic Peripheral Neuropathy isa serious complication of diabetes that often causes pain inthe limbs. Pain management Diabetic Peripheral Neuropathyis usually by administering pain medication for a long periodof time. These medicines will have side effects. The use ofacupuncture as an alternative to help reduce the intensity ofpain in peripheral diabetic neuropathy has proven to beeffective and relatively without side effects. The advantage ofacupuncture therapy is that it has relatively no side effects.The general aim of this study is to reduce the intensity of painin peripheral neuropathy. The research design usesquantitative methods. The study population was all patientswith peripheral neuropathy who visited the Harmoni HealthyClinic in March-May 2019. The sampling method used wasaccidental sampling. The benefits of this study provide analternative for DM sufferers to reduce the intensity ofneuropathic pain naturally with acupuncture without fear.side effects. From the results of this study it is known thatthere is an influence of Jin’s Three Needle acupuncture inreducing the intensity of pain in Peripheral Neuropathy.Calculations using statistical SPSS 21 with paired sample ttest obtained significant results (0.00) from the value of α(0.05), then H1 is accepted. So with a significance level of5%, it can be concluded that Jin's Three Needle acupuncturecan reduce the intensity of pain in diabetic peripheralneuropathy


2019 ◽  
Vol 48 (1) ◽  
pp. 59-70 ◽  
Author(s):  
Lisa M. Mangus ◽  
Deepa B. Rao ◽  
Gigi J. Ebenezer

Analysis of intraepidermal nerve fibers (IENFs) in skin biopsy samples has become a standard clinical tool for diagnosing peripheral neuropathies in human patients. Compared to sural nerve biopsy, skin biopsy is safer, less invasive, and can be performed repeatedly to facilitate longitudinal assessment. Intraepidermal nerve fiber analysis is also more sensitive than conventional nerve histology or electrophysiological tests for detecting damage to small-diameter sensory nerve fibers. The techniques used for IENF analysis in humans have been adapted for large and small animal models and successfully used in studies of diabetic neuropathy, chemotherapy-induced peripheral neuropathy, HIV-associated sensory neuropathy, among others. Although IENF analysis has yet to become a routine end point in nonclinical safety testing, it has the potential to serve as a highly relevant indicator of sensory nerve fiber status in neurotoxicity studies, as well as development of neuroprotective and neuroregenerative therapies. Recently, there is also interest in the evaluation of IENF via skin biopsy as a biomarker of small fiber neuropathy in the regulatory setting. This article provides an overview of the anatomic and pathophysiologic principles behind IENF analysis, its use as a diagnostic tool in humans, and applications in animal models with focus on comparative methodology and considerations for study design.


2021 ◽  
Vol 2 ◽  
Author(s):  
Pallai Shillo ◽  
Yiangos Yiangou ◽  
Philippe Donatien ◽  
Marni Greig ◽  
Dinesh Selvarajah ◽  
...  

Painful diabetic peripheral neuropathy can be intractable with a major impact, yet the underlying pain mechanisms remain uncertain. A range of neuronal and vascular biomarkers was investigated in painful diabetic peripheral neuropathy (painful-DPN) and painless-DPN and used to differentiate painful-DPN from painless-DPN. Skin biopsies were collected from 61 patients with type 2 diabetes (T2D), and 19 healthy volunteers (HV). All subjects underwent detailed clinical and neurophysiological assessments. Based on the neuropathy composite score of the lower limbs [NIS(LL)] plus seven tests, the T2D subjects were subsequently divided into three groups: painful-DPN (n = 23), painless-DPN (n = 19), and No-DPN (n = 19). All subjects underwent punch skin biopsy, and immunohistochemistry used to quantify total intraepidermal nerve fibers (IENF) with protein gene product 9.5 (PGP9.5), regenerating nerve fibers with growth-associated protein 43 (GAP43), peptidergic nerve fibers with calcitonin gene-related peptide (CGRP), and blood vessels with von Willebrand Factor (vWF). The results showed that IENF density was severely decreased (p < 0.001) in both DPN groups, with no differences for PGP9.5, GAP43, CGRP, or GAP43/PGP9.5 ratios. There was a significant increase in blood vessel (vWF) density in painless-DPN and No-DPN groups compared to the HV group, but this was markedly greater in the painful-DPN group, and significantly higher than in the painless-DPN group (p < 0.0001). The ratio of sub-epidermal nerve fiber (SENF) density of CGRP:vWF showed a significant decrease in painful-DPN vs. painless-DPN (p = 0.014). In patients with T2D with advanced DPN, increased dermal vasculature and its ratio to nociceptors may differentiate painful-DPN from painless-DPN. We hypothesized that hypoxia-induced increase of blood vessels, which secrete algogenic substances including nerve growth factor (NGF), may expose their associated nociceptor fibers to a relative excess of algogens, thus leading to painful-DPN.


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