الفهرس 
Diabetic NeuropathyOnly 14 pages are availabe for public view
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Abstract
Diabetes is a major public health problem that is becoming more prevalent worldwide.DN is one of its frequent and costly complications and is usually related to the duration and severity of hyperglycemia. Epidemiology of DN is still unclear because of the multiple diagnostic criteria, inability of many physician to identify the disease and poor methodology to evaluate the patients. DSP is the most common form of DN. Pathogenesis of DN is still poorly understood. Hypothesis such as increased polyol pathway flux; increase hexosamine pathway flux, advanced glycation end products formation, activation of PKC, oxidative stress, PARP activation, inflammation, and decreased neurotrophines are all suggested to play a major role in that development of DN. There are many animal models of DN, which are useful to investigate the pathogenesis of neuropathy and to evaluate different lines of therapy.
Animal models include In vitro and in vivo models. In vitro models allow investigators to answer mechanistic questions that cannot be answered in animal models by allowing the study of a single variable. In vitro model include primary cultures, organotypic cultures and transformed cell line. In vivo models are subdivided into: spontaneous genetic models, genetically engineered animal models as transgenic and knockout models and chemically induced models. Streptozotocin is one of the most widely used models as it is relatively cheap, can induce both types of diabetes and it is easy to develop and maintain. Nutritionally induced diabetes have the advantages of the development of diabetes associated with obesity secondary to over nutrition mimicking type 2 diabetes. The absence of verbal communication represents an obstacle to the evaluation of pain in animals. DN can be assessed in animal models using behavioral tests, functional tests, structural and molecular biomarkers. Functional tests include NCSs and reduced nerve blood flow. Structural biomarkers include epidermal nerve fiber quantification.
Screening for neuropathy is an important component of routine diabetes care and diagnosis and staging of DN is an important tool for the evaluation of new therapeutics in clinical trials. This includes a history-symptom questionnaire followed by physical examination including the inspection of feet abnormalities, quantitative sensation tests such as SWM and VPT tests as well as ankle reflexes and pin prick tests. This examination is then followed by NCSs. Recently there are new diagnostic modalities as skin biopsy and skin blood flow.
Treatment of DN is based on three cornerstones. The first cornerstone is interventions aiming for normoglycemia. The second cornerstone is drugs that target pathogenic mechanisms, most of which are still in clinical development. These drugs may support adult neurons and directly repair nerves after injury and include many disease-modifying drugs such as ARIs, Antiglycation compounds, PKC inhibitors, Poly (ADP-ribose) polymerase inhibitors, antioxidants and GF therapies. The third cornerstone is symptomatic treatment for painful neuropathy, which include certain antidepressants and dual reuptake inhibitors of both 5-HT and NE, gabapentin, pregabalin, and topical lidocaine as 1st line of treatment. Opioid analgesics and tramadol are recommended generally as a second-line treatments that can be considered for first-line use in selected clinical circumstances. Other medications that would generally be used as third-line treatments but that could also be used as second-line treatments in some circumstances include certain antiepileptic and antidepressant medications.
It is concluded that despite the importance of DN as the most frequent complication of diabetes and its tremendous impact on patients’ quality of life, there is no effective treatment for it. Further studies on the pathophysiological mechanisms are needed to develop new pharmaceutical agents that may help these patients.