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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuropathic pain can seem enigmatic at first because it can last indefinitely and often a cause is not evident. However, heightened awareness of typical characteristics, such as the following, makes identification fairly easy: The presence of certain accompanying conditions (e.g., diabetes, HIV or herpes zoster infection, multiple sclerosis) Pain described as shooting, stabbing, lancinating, burning, or searing Pain worse at night Pain following anatomic nerve distribution Pain in a numb or insensate site The presence of allodynia Neuropathic pain responds poorly to standard pain therapies and usually requires specialized medications (e.g., anticonvulsants, tricyclic antidepressants, opioid analgesics) for optimal control. Successful pain control is enhanced with use of a systematic approach consisting of disease modification, local or regional measures, and systemic therapy.
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PMID:Following the clues to neuropathic pain. Distribution and other leads reveal the cause and the treatment approach. 1057 7

The usefulness of sensory symptoms in the assessment of diabetic polyneuropathy is unclear. In the present study, we studied the hypothesis that pain is associated with small nerve fibre function, and that sensory alteration is associated with large nerve fibre function. In addition, we assessed the reproducibility and the ability to detect changes in clinical status over time of the nerve function tests currently used in clinical trials. Patients (78) with stable diabetic polyneuropathy were examined on three separate occasions with a test-retest interval of 17 and 52 weeks. Small nerve fibre function was measured using temperature discrimination thresholds for warmth (TDTwarmth) and cold (TDTcold). Large nerve fibre function was measured by testing sensory and motor nerve conduction velocities (SNCV and MNCV) and vibration perception thresholds (VPT). Neuropathic pain was only significantly associated with TDTcold, and with the MNCV of the tibial nerve. Sensory alteration was associated with almost all nerve function tests except the SNCV and MNCV of the ulnar nerve. The measurements of symptom severity and the nerve function tests all proved to be sufficiently reproducible. The standardized smallest detectable difference on group level (SDD) of the measurement of sensory alteration and neuropathic pain were almost the same (9% and 12%, respectively). Among the nerve function tests, the SNCV and MNCV had the smallest SDD (3-4%), and were, therefore, potentially the most responsive instruments. The SDD of the TDT was greater than the VPT (9-14% vs 21-28%, respectively). In conclusion, neuropathic pain was not associated with small nerve fibre function, and sensory alteration was associated with both large and small fibre function. In addition, the standardized measurement of symptom severity, the SNCV and MNCV tests, and the VPT test appear to be useful for monitoring the course of polyneuropathy in clinical trials.
Diabetes Res Clin Pract 2000 Feb
PMID:Methods for assessing diabetic polyneuropathy: validity and reproducibility of the measurement of sensory symptom severity and nerve function tests. 1067 Sep 7

Treatment of neuropathic pain is the primary focus of management for many patients with painful peripheral neuropathies. Neuropathic pain is a common feature of many peripheral neuropathies including those associated with diabetes, uremia, HIV infection, and alcohol abuse. Pain is also present in the majority of patients with idiopathic sensory and sensorimotor polyneuropathies. A growing number of pharmacologic agents are available for the treatment of neuropathic pain. The medications that have undergone the most rigorous study are the tricyclic antidepressants and anticonvulsants. These two families of medications are widely used and represent first-line agents in the management of neuropathic pain. Pain management should begin with a concerted effort to identify the etiology of the neuropathy, as directed therapy may help alleviate the symptoms. When initiating pharmacotherapy for neuropathic pain, one must individualize treatment and choose an agent that is likely to be tolerated, as adverse events are not uncommon for some of the medications. Treatment of neuropathic pain remains challenging, with considerable variability in an individual's response to the various agents and even to different drugs in the same class. However, monotherapy with a well-chosen agent or rational polypharmacy that combines medications with different mechanisms of action will benefit a majority of patients with neuropathic pain.
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PMID:Painful Peripheral Neuropathy. 1193 24

Neuropathic pain is a common phenomenon resulting from injury to the central or peripheral nervous system. The means by which diabetes results in nerve injury is unclear but the effect is to cause injury at all levels of the nervous system from the level of the peripheral nerves to the brain. Nerve injury causes pain through a cascade of mechanisms resulting in altered processing of sensory input into the nervous system. This alteration occurs through chemical and anatomical changes in the nervous system that are similar to some of the processes seen in central sensitisation following acute pain. Following nerve injury, neuropathic pain occurs not only when these mechanisms are activated but also when sensitisation is maintained. Other processes occurring in neuropathic pain appear to be a loss of normal inhibitory controls as seen by a reduction in local GABA-ergic and descending monoaminergic influences. There are also important changes mediated via glial cells that can maintain neuropathic pain. Diabetes affects all areas of the nervous system and the contribution of higher levels of the nervous system is often overlooked. Neurophysiological and MRI evidence strongly suggest that these may contribute to the pain of diabetic neuropathy. Psychological dysfunction in diabetic patients is an important factor in increasing the suffering associated with all aspects of the disease, but treatment and control of pain can greatly improve the quality of life.
Diabetes Metab Res Rev
PMID:Neuropathic pain and diabetes. 1257 53

Neuropathic pain is one of the important microvascular complications of diabetes. Oxidative stress and superoxide play a critical role in the development of neurovascular complications in diabetes. Aim of the present study was to evaluate the effect of quercetin, a bioflavonoid on thermal nociceptive responses in streptozotocin (STZ)-induced diabetic rats assessed by tail-immersion and hot plate methods. After 4-weeks of a single intravenous STZ injection (45 mg/kg body weight), diabetic rats exhibited a significant thermal hyperalgesia and cold allodynia along with increased plasma glucose and decreased body weights as compared with control rats. Chronic treatment with quercetin (10 mg/kg body weight; p.o) for 4-weeks starting from the 4th week of STZ-injection significantly attenuated the cold allodynia as well as hyperalgesia. Results indicate that quercetin, a natural antioxidant, may be helpful in diabetic neuropathy.
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PMID:Quercetin attenuates thermal hyperalgesia and cold allodynia in STZ-induced diabetic rats. 1557 24

Prediabetes is associated with a length-dependent polyneuropathy that typically is sensory predominant and painful. A diagnosis of prediabetes should be sought in patients with otherwise idiopathic sensory-predominant neuropathy by doing a 2-hour oral glucose tolerance test. Fasting plasma glucose of 100 to 125 mg/dL or 2-hour glucose 140 to 199 mg/dL (impaired glucose tolerance) constitutes prediabetes. Most patients with neuropathy associated with prediabetes (NAP) are obese and show metabolic manifestations of insulin resistance, including hyperlipidemia and hypertension. Appropriate treatment addresses hyperglycemia, insulin resistance, and neuropathic pain. Professionally administered individualized diet and exercise counseling (modeled on the Diabetes Prevention Program) has been shown to be more effective than glucose-lowering medications in preventing progression from impaired glucose tolerance to diabetes, and is the mainstay of treatment for all patients with NAP. The goals of this therapy should be a 5% to 7% reduction in weight and an increase to 30 minutes of moderate exercise five times weekly. Patients with prediabetes are at increased risk for myocardial infarction, stroke, and peripheral vascular disease. Therefore, risk reduction with control of hypertension and hyperlipidemia is essential. Neuropathic pain troubles nearly every patient with NAP, and often limits aerobic exercise. No trials have specifically addressed the patient population with NAP, and neuropathic pain treatment closely follows recommendations for diabetic neuropathy. Gabapentin, lamotrigine, and tricyclic antidepressants are well-validated first-line therapies. Adjunctive therapy with opioids, nonsteroidal anti-inflammatory drugs often are necessary. Diet and exercise seem to reduce neuropathic pain in patients with NAP.
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PMID:Polyneuropathy with Impaired Glucose Tolerance: Implications for Diagnosis and Therapy. 1561 Jul 5

Neuropathic pain is a common and severely disabling state that affects millions of people worldwide. Such pain can be experienced after nerve injury or as part of diseases that affect peripheral nerve function, such as diabetes and AIDS; it can also be a component of pain in other conditions, such as cancer. Following peripheral nerve injury, microglia in the spinal cord become activated. Recent evidence indicates that activated microglia are key cellular intermediaries in the pathogenesis of nerve injury-induced pain hypersensitivity because P2X(4) purinoceptors and p38 mitogen-activated protein kinase, which are present in activated microglia, are required molecular mediators. It is important to establish how these molecules are activated in spinal microglia following nerve injury and how they cause signaling to neurons in the dorsal horn pain transmission network. Answers to these questions could lead to new strategies that assist in the diagnosis and management of neuropathic pain--strategies not previously anticipated by a neuron-centric view of pain plasticity in the dorsal horn.
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PMID:Neuropathic pain and spinal microglia: a big problem from molecules in "small" glia. 1566 33

Neuropathic pain and fibromyalgia are prevalent diseases which have major consequences on healthcare resources and the individual. From the clinical point of view neuropathic pains represent a heterogeneous group of aetiologically different diseases ranging from cancer to diabetes. Patients with fibromyalgia also display clinical features common in neuropathic pain suggesting that there might be some overlap. The mechanisms responsible for symptoms and signs in both diseases are still unknown. Recently, there have been numerous reports of various pharmacological treatments of neuropathic pain and fibromyalgia with often disappointing results. Most of the studies were of short duration, had high attrition rates, and displayed other methodological problems. Some compounds had high rates of adverse effects which makes it often difficult for the patients to tolerate the treatment, especially in the long-term. At present, the best options for medication treatment are tricyclic antidepressants in lower dosage than usual in psychiatric disorders and a wide range of anticonvulsants. Opioids are sometimes recommended but have been found to have minor efficacy. Recently, there have been more controlled trials, which are reported here if they had been published between 2002 and 2004. Various compounds have been tested in different studies. Treatment of fibromyalgia, which has many features in common with depressive symptoms, became the focus of interest. New promising studies with dual serotonin-norepinephrine reuptake inhibitors (duloxetine and milnacipram) and a newer antiepileptic drug (pregabalin) are in progress. Future research will have to apply new approaches (e.g., using a mechanism-based classification of neuropathic pain and carrying out studies in populations with the same symptom but not necessarily the same disease) in order to find effective treatments for these common and often debilitating diseases.
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PMID:Current trends in neuropathic pain treatments with special reference to fibromyalgia. 1590 59

Microglia play an important role as immune cells in the central nervous system (CNS). Microglia are activated in threatened physiological homeostasis, including CNS trauma, apoptosis, ischemia, inflammation, and infection. Activated microglia show a stereotypic, progressive series of changes in morphology, gene expression, function, and number and produce and release various chemical mediators, including proinflammatory cytokines that can produce immunological actions and can also act on neurons to alter their function. Recently, a great deal of attention is focusing on the relation between activated microglia through adenosine 5'-triphosphate (ATP) receptors and neuropathic pain. Neuropathic pain is often a consequence of nerve injury through surgery, bone compression, diabetes, or infection. This type of pain can be so severe that even light touching can be intensely painful and it is generally resistant to currently available treatments. There is abundant evidence that extracellular ATP and microglia have an important role in neuropathic pain. The expression of P2X4 receptor, a subtype of ATP receptors, is enhanced in spinal microglia after peripheral nerve injury model, and blocking pharmacologically and suppressing molecularly P2X4 receptors produce a reduction of the neuropathic pain. Several cytokines such as interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) in the dorsal horn are increased after nerve lesion and have been implicated in contributing to nerve-injury pain, presumably by altering synaptic transmission in the CNS, including the spinal cord. Nerve injury also leads to persistent activation of p38 mitogen-activated protein kinase (MAPK) in microglia. An inhibitor of this enzyme reverses mechanical allodynia following spinal nerve ligation (SNL). ATP is able to activate MAPK, leading to the release of bioactive substances, including cytokines, from microglia. Thus, diffusible factors released from activated microglia by the stimulation of purinergic receptors may have an important role in the development of neuropathic pain. Understanding the key roles of ATP receptors, including P2X4 receptors, in the microglia may lead to new strategies for the management of neuropathic pain.
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PMID:The function of microglia through purinergic receptors: neuropathic pain and cytokine release. 1616 95

Neuropathic pain is responsible for a significant amount of the morbidity associated with generalized and focal peripheral neuropathies in diabetes. It is a consequence of alterations in neuronal function, chemistry, and structure that occur secondary to nerve injury. A variety of agents from diverse pharmacologic classes, the so-called adjuvant analgesics, have been used to treat neuropathic pain. These include antidepressants, first- and second-generation anticonvulsants, antiarrhythmic agents, topical agents, N-methyl-d-aspartate receptor antagonists, and the opioid analgesics. The availability of several newer agents, used alone or in combination, has resulted in the successful alleviation of neuropathic pain in many patients. Recent advances in the understanding of pain mechanisms at multiple central nervous system levels should pave the way toward more effective treatment modalities with less prominent side effects.
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PMID:Newer agents for the treatment of painful diabetic peripheral neuropathy. 1631 90


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