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 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diabetic neuropathy is the most common neuropathy in industrialized countries, and it is associated with a wide range of clinical manifestations. The vast majority of patients with clinical diabetic neuropathy have a distal symmetrical form of the disorder that progresses following a fiber-length-dependent pattern, with sensory and autonomic manifestations predominating. This pattern of neuropathy is associated with a progressive distal axonopathy. Patients experience pain, trophic changes in the feet, and autonomic disturbances. Occasionally, patients with diabetes can develop focal and multifocal neuropathies that include cranial nerve involvement and limb and truncal neuropathies. This neuropathic pattern tends to occur after 50 years of age, and mostly in patients with long-standing diabetes mellitus. Length-dependent diabetic polyneuropathy does not show any trend towards improvement, and either relentlessly progresses or remains relatively stable over a number of years. Conversely, the focal diabetic neuropathies, which are often associated with inflammatory vasculopathy on nerve biopsies, remain self-limited, sometimes after a relapsing course.
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PMID:Diabetic neuropathy--a review. 1754 59

Depression and painful somatic symptoms commonly occur together. Depression and chronic pain can have devastating effects on a patient's health, productivity, and overall quality of life. When moderate-to-severe pain exists, it can impair patient function while making treatment more difficult or resistant, with increased severity in depressive symptoms and worse outcomes. A variety of chronic pain syndromes exist, including diabetic neuropathy. A high prevalence of patients with chronic pain display depressive symptoms. Treatment for these conditions relies on pharmacologic therapy coupled with diligent, periodic assessments of changes in symptom severity. The link between pain and depression lies in the central and peripheral nervous systems. The brain stem serves as an important connection between the higher brain centers and the spinal cord. In the brain stem, the neurotransmitters serotonin and norepinephrine modulate pain transmission through ascending and descending neural pathways. Both serotonin and norepinephrine are also key neurotransmitters involved with the pathophysiology of depression. Tricyclic antidepressants are effective treatments for pain and depression; selective serotonin reuptake inhibitors provide less benefit. Duloxetine and venlafaxine, which are serotonin and norepinephrine reuptake inhibitors, were shown in clinical trials to alleviate pain and depressive symptoms. Diabetic neuropathy and other chronic pain syndromes were also shown to benefit from duloxetine and venlafaxine. Antidepressants remain fundamental therapeutic agents for depression and anxiety disorders. Their extended use into chronic pain, depression with physical pain, physical pain with or without depression, and other potential medical conditions should be recognized.
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PMID:Antidepressant agents for the treatment of chronic pain and depression. 1796 65

Diabetic neuropathy is the commonest form of peripheral neuropathy in the developed countries of the world. In diabetic patients, the presence of peripheral neuropathy increases their risks for developing foot ulceration and subsequent necrosis that necessitates lower limb amputation. Although the precise mechanisms underlying diabetic neuropathy remain unclear, there is evidence that hyperglycemia-induced formation of advanced glycation end products (AGEs) is related to diabetic neuropathy; AGE-modified peripheral nerve myelin is susceptible to phagocytosis by macrophages and contributes to segmental demyelination; modification of major axonal cytoskeletal proteins such as tubulin, neurofilament, and actin by AGEs results in axonal atrophy/degeneration and impaired axonal transport; and glycation of extracellular matrix protein laminin leads to impaired regenerative activity in diabetic neuropathy. Recently, the receptor for AGEs (RAGE) has been found to colocalize with AGEs in diabetic peripheral nerves. This suggests that, in diabetic neuropathy, AGEs and AGE/RAGE interactions induce oxidative stress, result in upregulation of nuclear factor (NF)-kappaB and various NF-kappaB-mediated proinflammatory genes, and exaggerate neurological dysfunction, including altered pain sensation. Additionally, AGE/RAGE-induced oxidative stress further accelerates formation of glycoxidation products such as Nepsilon-(carboxymethyl)lysine and pentosidine. Although new drugs that inhibit the formation of AGEs and block the AGE-RAGE interaction are being studied, no effective treatment modalities against AGE-induced nerve injury are currently available clinically. A therapeutic strategy to prevent and ameliorate diabetic neuropathy using anti-AGE agents needs to be established. In this review, the current issues involved in the role of the glycation process and the potential treatment options for diabetic neuropathy are explored.
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PMID:Role of advanced glycation end products in diabetic neuropathy. 1847 45

The podiatric physician often encounters complex painful neuropathies in daily practice. Diabetic neuropathy is one form of chronic neuropathic pain dealt with on a regular basis. The goal of this article is to review the pathophysiology, diagnosis, and treatment options of this complaint. Medical and surgical interventions are discussed, with a clinical emphasis on patient selection and prevention.
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PMID:Painful diabetic neuropathy. 1848 49

Neuropathy is the most common and debilitating complication of diabetes and results in pain, decreased motility, and amputation. Diabetic neuropathy encompasses a variety of forms whose impact ranges from discomfort to death. Hyperglycemia induces oxidative stress in diabetic neurons and results in activation of multiple biochemical pathways. These activated pathways are a major source of damage and are potential therapeutic targets in diabetic neuropathy. Though therapies are available to alleviate the symptoms of diabetic neuropathy, few options are available to eliminate the root causes. The immense physical, psychological, and economic cost of diabetic neuropathy underscore the need for causally targeted therapies. This review covers the pathology, epidemiology, biochemical pathways, and prevention of diabetic neuropathy, as well as discusses current symptomatic and causal therapies and novel approaches to identify therapeutic targets.
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PMID:Diabetic neuropathy: mechanisms to management. 1861 62

Diabetic neuropathy is a heterogeneous disease with diverse pathology. Recognition of the clinical homolog of these pathologic processes is necessary in achieving appropriate intervention. Treatment should be individualized so the particular manifestation and underlying pathogenesis of each patient's clinical presentation are considered. In older adults, special care should be taken to manage pain while optimizing daily function and mobility, with the fewest adverse medication side effects. Older adults are at great risk for falling and fractures because of instability and weakness, and require strength exercises and coordination training. Ultimately agents that address large fiber dysfunction will be essential to reduce the gross impairment of quality of life and activities of daily living that neuropathy visits older people who have diabetes.
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PMID:Diabetic neuropathy in older adults. 1867 80

Diabetic neuropathy represents late diabetes complications, and diabetes duration and long-term hyperglycemia are the main reasons for polyneuropathy. The goal was to estimate the effects of alpha-lipoic acid on symptoms of diabetic neuropathy after 600 mg i.v. for 3 weeks and 3 months of 300-600 mg of alpha-lipoic acid per os. This study has been designed as a multicentric, in 5-centers in B&H, carried out by 5 physicians with 20 diabetic patients each. Following parameters were monitored in 100 diabetics suffering from Type 1 and Type 2 diabetes, both men and women: diabetes duration, diabetes therapy, duration of polyneuropathy symptoms, height, weight, BMI (body mass index), subjective assessment of patients, objective examinations of physicians and subjective assessment of physicians. 100 diabetics, average age 61,36; oldest 79, youngest 40, suffered from diabetes in average 11,9 years. There were 35 men and 65 women, 16 with Type 1 and 80 with Type 2 diabetes, while 4 patients were not classified. 69 were having insulin therapy and 31 oral hypoglicemics. Shortest diabetic status was less than a year, and longest was 28 years. Average duration of polyneuropathic symptoms was 3,02 years, shortest was less than a year, and the longest was 15 years. Average height was 1,70 m, average weight 76,13 kg, and average BMI 26,51 kg/m2. Significant statistic differences in improvement were recorded (P>0,05) according to Fridman's test for repeated measurements compared to initial findings in assessments: sensory symptoms of polyneuropathy, pain sensations as polyneuropathy symptoms, total score of polyneuropathy symptoms, subjective assessment of patients, subjective findings of physicians, and significant differences were not find (P>0,05) in autonomous and motoric neuropathy. Based on the conducted study, we have concluded that the application of alpha-lipoic acid during 3 months has helped to decrease the symptoms of diabetic neuropathy and in only one case out of 100 included patients there was no subjective improvement after drug application.
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PMID:The role of alpha-lipoic acid in diabetic polyneuropathy treatment. 1912 5

About 60 to 70 percent of people with diabetes have some neuropathy. Diabetic neuropathy can be classified as peripheral, autonomic, proximal, focal and multifocal or mixed. Peripheral neuropathy, the most common type of diabetic neuropathy, causes pain and/or loss of feeling in the toes, feet, legs, hands, and arms; extreme sensitivity to touch, loss of balance and coordination; muscle weakness and loss of reflexes, especially at the ankle, leading to changes in the way a person walks. The aim of this study is to underline the importance of drug and rehabilitative approach in the therapy of peripheral neuropathy, that frequently influences both diabetes mellitus type 1 and diabetes mellitus type 2.
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PMID:[Diabetic peripheral neuropathy: reflections and drug-rehabilitative treatment]. 1972 72

Diabetic neuropathy is one of the most common complications of diabetes and causes various problems in daily life. Several investigations have noted that many factors in the spinal cord are involved in the symptoms of painful diabetic neuropathy, and there are very few effective therapeutic regimens. In the present study, we sought to elucidate the role of the RhoA/Rho kinase (ROCK) pathway in thermal hyperalgesia in diabetic mice. The intracellular localization of RhoA and the expression of eNOS were measured by western blotting. Thermal hyperalgesia was assessed by the tail-flick test and mechanical allodynia was assessed by automated von Frey filament test in streptozotocin(STZ)-induced diabetic mice. The spinal cord of STZ-treated diabetic mice showed increased membrane-bound RhoA compared to non-diabetic control. Treatment with the RhoA inhibitor exoenzyme C3, Clostridium botulinum, and the ROCK inhibitor Y27632 attenuated thermal hyperalgesia and mechanical allodynia in diabetic mice. Moreover, daily treatment with simvastatin attenuated all of those changes in diabetic mice. The expression of eNOS and NO metabolite contents in the spinal cord was decreased in diabetic mice, and these changes were normalized by treatment with simvastatin. The present results show that HMG-CoA reductase inhibitors have an inhibitory effect on thermal hyperalgesia in diabetic mice, which is mediated by an increase in NO production through the inhibition of RhoA/ROCK pathways. These results suggest that ROCK inhibitors and HMG-CoA inhibitors may be attractive compounds to relieve the symptoms of painful diabetic neuropathies.
Pain 2011 Jan
PMID:RhoA/Rho kinase pathway contributes to the pathogenesis of thermal hyperalgesia in diabetic mice. 2098 Jan 2

In the industrialized world, polyneuropathy induced by diabetes mellitus (DM) is one of the most prevalent forms of neuropathy. Diabetic neuropathy can result from a direct toxic effect of glucose on nerve cells. Additionally, the damage of the nerve structures (central and peripheral) is accompanied by a microvascular dysfunction, which damages the vasa nervorum. More than 80% of the patients with DM-induced polyneuropathy have a distal and symmetric presentation. The initial symptoms are: signs of diminished sensation, burning feet, which may occur particularly during the night and worsen when touched, and tingling sensation in the feet. Attacks of shooting pain may also occur. Proper control of DM is mandatory. Based on the recently published National Institute for Health and Clinical Excellence guidelines, treatment of painful diabetic neuropathy should start with duloxetine or amitriptyline if duloxetine is contraindicated. If pain relief is inadequate, monotherapy with amitriptyline or pregabalin, or combination therapy with amitriptyline and pregabalin should be considered. If pain relief is still insufficient, tramadol instead of or in combination with a second-line agent should be considered. In patients who are unable to take oral medication, topical lidocaine can be considered for localized pain. There are currently four studies showing that spinal cord stimulation can potentially provide pain alleviation for the longer term in patients with painful diabetic polyneuropathy. Complications are mainly implant related, though infections also occur. The available evidence (2 C+) justifies spinal cord stimulation to be considered, preferably study related.
Pain Pract
PMID:Evidence-based interventional pain medicine according to clinical diagnoses. 18. Painful diabetic polyneuropathy. 2119 15


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