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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diabetic polyneuropathy is the most frequent neuropathy in western countries. In Germany, there are 3.5 to 4 million diabetic patients. Diagnosis should rule out other polyneuropathies and assess two out of the five diagnostic criteria: neuropathic symptoms, neuropathic deficits, pathological nerve conduction studies, pathological quantitative sensory testing and pathological quantitative autonomic testing. So far, the pathophysiology of diabetic neuropathy remains to be fully understood. Among the various pathophysiological concepts are the Sorbitol-Myo-Inositol hypothesis attributing Myo-Inositol depletion to the accumulation of Sorbitol and Fructose, the concept of deficiency of essential fatty acids with reduced availability of gamma-linolenic-acid and prostanoids, the pseudohypoxia- and hypoxia-hypothesis attributing endothelial and axonal dysfunction and structural lesions to increased oxidative stress and free radical production. Obviously, the hyperglycemia induced generation of advanced glycation end products (AGEs) also contributes to structural dysfunctions and lesions. Elevated levels of circulating immune complexes and activated T-lymphocytes as well the identification of autoantibodies against vagus nerve or sympathetic ganglia support the concept of an immune mediated neuropathy. The reduction of neurotrophic factors such as nerve growth factor, neurotrophin-3 or insulin-like growth factors also seems to further diabetic neuropathy. The symmetrical, distally pronounced and predominantly sensory neuropathy is far more frequent than the symmetrical neuropathy with predominant motor weakness or the asymmetrical neuropathy. The painless neuropathy manifests with impaired light touch sensation, position sense, vibratory perception and diminished or absent ankle deep tendon reflexes. The painful sensory diabetic neuropathy primarily affects small nerve fibers and accounts for decreased temperature perception and paresthesias. The proximal, diabetic amyotrophy evolves subacutely or acutely, induces motor weakness of the proximal thigh and buttock muscles and is painful. Cranial nerve III-neuropathy is also painful and has an acute onset. Truncal radiculopathy follows the distribution of truncal roots and frequently causes intense pain. Autonomic neuropathy occurs with and without somatic neuropathy. The most important therapy is to attempt optimal blood glucose control, to reduce body weight and hyperlipidemia. Symptomatic therapy includes alpha-lipoic acid treatment, as the antioxidant seems to improve neuropathic symptoms. Aldose reductase inhibitors might reduce sorbitol and fructose production and normalize myo-inositol levels. However, there are no aldose reductase inhibitors available in Europe as yet. Evening primrose oil, containing gamma-linolenic acid, might improve nerve conduction velocities, temperature perception, muscle strength, tendon reflexes and sensory function. Substitution of nerve growth factor showed promising results in pilot studies but failed in a large-scale multicenter study. Symptomatic pain treatment can be achieved with tricyclic antidepressants, selective serotonin reuptake inhibitors, anticonvulsants such as carbamazepine, gabapentin or lamotrigine, or anti-arrhythmic drugs such as mexiletine. Topical capsaicin application should reduce neuropathic pain but also induces local discomfort in the beginning of therapy. Vasoactive substances, so far have not proven to be of major benefit in diabetic neuropathy. Physical therapy and thorough footcare are of primary importance and allow prevention of secondary complications such as foot amputations.
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PMID:[Diabetic somatic polyneuropathy. Pathogenesis, clinical manifestations and therapeutic concepts]. 1092 53

Diabetic polyneuropathy (DPN) is the most common complication of diabetes and may frequently be the presenting symptom in type 2 diabetes mellitus (T2DM). Metabolic syndrome and T2DM are associated with multiple metabolic toxicities. These substrate toxicities support the formation of reactive oxygen species (ROS), which are so damaging to cells, tissues and organs and play an important role in the development of multiple diabetic complications. The importance of redox stress (ROS) and their effect on the neuronal unit are discussed. There are at least 5 major pathways involved in the development of DPN: metabolic, vascular, immunologic-autoimmune, neurohormonal growth factor deficiency, and extracellular matrix neuronal unit remodeling. Each of these five pathways are reviewed and related to neural redox stress and the role of ROS. The identification of the toxic substrates (A-FLIGHT acronym), earlier diagnosis of T2DM at the stage of impaired glucose tolerance or impaired fasting glucose, and aggressive global risk reduction with the use of a simple RAAS acronym will assist the clinician in slowing the natural progressive history, and possibly preventing the complications associated with DPN. The pain, foot ulceration, limb loss, organ dysfunction, and the associated morbidity and financial burden all contribute to the need for a better understanding of DPN and the role of redox stress and global risk reduction.
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PMID:Neural redox stress and remodeling in metabolic syndrome, type 2 diabetes mellitus, and diabetic neuropathy. 1556 93

Diabetics develop numerous chronic associated diseases, among them sensory polyneuropathy. Diabetic polyneuropathy (DPN) often causes pain of various kinds, degree and duration. There are many pharmacological approaches: antidepressants are also important. Duloxetine is a recently approved dual action serotonin and noradrenaline re-uptake inhibitor that in its analgesic efficacy is comparable to established drugs. Duloxetine, in a dosage of 60 mg x 1 or x 2 daily, significantly reduces, from the first week of administration, the pain of DPN, when compared with a placebo. The most commonly observed side effects have been nausea, sleepiness, constipation and fatigue. On average duloxetine has not shown any clinically relevant increase in blood pressure, pulse rate and weight. It thus offers a new option as part of the treatment of pain caused by DPN. The various drugs should be considered individually in any treatment algorithm, also taking into account their side effects. Psychotherapeutic methods serve to support the overcoming of pain.
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PMID:[Duloxetine, a new therapeutic option for diabetic peripheral neuropathic pain]. 1713 88

Diabetes targets the peripheral nervous system with several different patterns of damage and several mechanisms of disease. Diabetic polyneuropathy (DPN) is a common disorder involving a large proportion of diabetic patients, yet its pathophysiology is controversial. Mechanisms considered have included polyol flux, microangiopathy, oxidative stress, abnormal signaling from advanced glycation endproducts and growth factor deficiency. Although some clinical trials have demonstrated modest benefits in disease stabilization or pain therapy in DPN, robust therapy capable of reversing the disease is unavailable. In this review, general aspects of DPN and other diabetic neuropathies are examined, including a summary of recent therapeutic trials. A particular emphasis is placed on the evidence that the neurobiology of DPN reflects a unique yet common and disabling neurodegenerative disorder.
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PMID:Diabetes mellitus and the peripheral nervous system: manifestations and mechanisms. 1746 9

Diabetic polyneuropathy (DPN) is the most common late complication of diabetes mellitus. The underlying pathogenesis is multifaceted, with partly interrelated mechanisms that display a dynamic course. The mechanisms underlying DPN in type 1 and type 2 diabetes mellitus show overlaps or may differ. The differences are mainly due to insulin deficiency in type 1 diabetes which exacerbates the abnormalities caused by hyperglycaemia. Experimental DPN in rat models have identified early metabolic abnormalities with consequences for nerve conduction velocities and endoneurial blood flow. When corrected, the early functional deficits are usually normalised. On the other hand, if not corrected, they lead to abnormalities in lipid peroxidation and expression of neurotrophic factors which in turn result in axonal, nodal and paranodal degenerative changes with worsening of nerve function. As the structural changes progress, they become increasingly less amendable to metabolic interventions. In the past several years, experimental drugs--such as aldose reductase inhibitors, antioxidants and protein kinase C inhibitors--have undergone clinical trials, with disappointing outcomes. These drugs, targeting a single underlying pathogenetic factor, have in most cases been initiated at the advanced stage of DPN. In contrast, substitution of acetyl-L-carnitine (ALC) or C-peptide in type 1 DPN target a multitude of underlying mechanisms and are therefore more likely to be effective on a broader spectrum of the underlying pathogenesis. Clinical trials utilising ALC have shown beneficial effects on nerve conduction slowing, neuropathic pain, axonal degenerative changes and nerve fibre regeneration, despite relatively late initiation in the natural history of DPN. Owing to the good safety profile of ALC, early initiation of ALC therapy would be justified, with potentially greater benefits.
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PMID:Acetyl-L-carnitine in diabetic polyneuropathy: experimental and clinical data. 1769 89

60 patients with clinical features of symmetric diabetic polyneuropathy have been examined including 30 patients of main group who received cerebrolysin and 30 patients of control group treated with milgamma. The effectiveness of treatment was assessed by the dynamics of polyneuropathic disorders in scores on the Diabetic polyneuropathy scale and the NDS. Pain syndrome was measured with the VAS. The significant therapeutic effectiveness of cerebrolysin was revealed for some parameters measured.
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PMID:[Influence of cerebrolysin therapy on the dynamics of diabetic polyneuropathy symptoms]. 1977 Aug 30

Diabetic polyneuropathy is a complex set of clinical syndromes, which deplete various regions of the nervous system. The process leading to diabetic neuropathy is multi-factorial. Its symptoms are paresthesia, dysesthesia and pain. The signs of damage to the peripheral neurons are hypoesthesia, hypoalgesia, hyperesthesia and hyperalgesia, decreased tendon reflexes, and, possibly, weakness and muscle atrophy. There is no universal classification. Electromyoneurography is indispensable in the diagnosis of diabetic polyneuropathy. However, there is no agreement on the most sensitive parameter for an early diagnosis. One hundred patients with diabetes mellitus were examined in order to investigate the sensitivity of different electromyographic parameters. Electromyographic techniques proved to be entirely sensitive for the early diagnosis of diabetic polyneuropathy. Some of the parameters are more suitable for an early detection of peripheral nerve damage, and others, which are not so sensitive but easy to use and stable, are suitable to follow up the course of diabetic polyneuropathy.
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PMID:The sensitivity of electromyoneurography in the diagnosis of diabetic polyneuropathy. 2154 63

Diabetic polyneuropathy occurs in around 50% of diabetic patients. Its pathophysiological mechanism is not completely clarified and major occurrences boil down to the change in neural phenotype and vasa nervorum. As glucose neurotoxicity has been suggested by plenty of evidence, the aim of the study was to assess the effect of glycemia on the severity of diabetic polyneuropathy. Considering that some practical experiences point to serious complications in patients suffering from diabetes of shorter duration, another aim was to assess the effect of diabetes duration on the severity of related neuropathy. Clinical and electromyoneurographic examinations were performed in 100 patients with diabetic polyneuropathy free from any laboratory signs of renal failure. The effect of HbA1c value and duration of disease on clinical symptoms, signs and electrophysiological indicators of polyneuropathy was analyzed. Study results indicated that 78% of patients with diabetic polyneuropathy did not have well-regulated glycemia. Diabetes duration was associated with a growing number of sensory symptoms, among which the sensation of pain similar to electric shock was present in 63% of patients. In addition, it also had negative impact on the sensory and motor nerve conduction velocity. HbA1c influenced the whole range of electrophysiological indicators of diabetic polyneuropathy.
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PMID:Clinical and electrophysiological signs of diabetic polyneuropathy -- effect of glycemia and duration of diabetes mellitus. 2226 77

Diabetes is a chronic disease that requires continual medical care and patient self-management education in order to prevent acute complications and to reduce the risk of long-term complications. Diabetes is the leading known cause of neuropathy in developed countries, and neuropathy is the most common complication and the leading source of morbidity and mortality in diabetes patients. Diabetic polyneuropathy is primarily symmetric sensory neuropathy, initially affecting distal lower extremities. Patients have evidence of nerve damage at the time their diabetes is diagnosed in 10%-18% of cases, suggesting that even early impairment of glucose handling, classified as prediabetes, is associated with neuropathy. It is important to appreciate that there are other causes of neuropathy; these should be considered if there is any aspect of the history or clinical presentation suggesting features atypical of diabetic neuropathy. Diagnosis of diabetic neuropathy should be established according to clinical manifestations of the disease, laboratory findings (altered glucose metabolism) and results of electrophysiological examinations. Treatment of painful diabetic polyneuropathy rests on a two-pronged approach: modification of the underlying disease and control of pain symptoms. The goals of painful diabetic polyneuropathy pharmacotherapy should be reduction of pain for maximum relief commensurate with acceptable side effects and restoration/ improvement in functional measures and quality of life.
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PMID:Recommendations for diabetic polyneuropathy treatment. 2226 98

Diabetic polyneuropathy (DPN) has several forms of clinical presentation. It may be asymptomatic, or present with prominent sensory symptoms, including neuropathic pain. Clinical neurologic examination is helpful in identifying patients with distal sensory deficits, loss of deep tendon reflexes, early distal motor abnormalities and skin ulceration. Other causes of polyneuropathy are important to exclude. For serial evaluations and research purposes, several clinical severity grading scales have been developed.
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PMID:Clinical features of diabetic polyneuropathy. 2541 Feb 11


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