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Query: UMLS:C0423716 (Neuropathic pain)
 1,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuropathic pain accompanies peripheral nerve injury following a variety of insults including metabolic disorders, traumatic injury, and exposure to neurotoxins such as vincristine and taxol. Vincristine, a microtubule depolymerizing drug, produces a peripheral neuropathy in humans that is accompanied by painful paresthesias and dysesthesias (Sandler et al., [1969] Neurology 19:367-374; Holland et al. [1973] Cancer Res. 33:1258-1264). The recent development of an animal model of vincristine-induced neuropathy provides an opportunity to investigate mechanisms underlying this form of neuropathic pain. Systemic vincristine (100 microg/kg) produces hyperalgesia to mechanical stimuli during the second week of administration, which persists for more than a week (Aley et al. [1996] Neuroscience 73:259-265). To test the hypothesis that changes in microtubule structure in nociceptive sensory neurons accompany vincristine-induced hyperalgesia, we analyzed unmyelinated axons in saphenous nerves of vincristine-treated rats. This study constitutes the first quantitative ultrastructural analysis of the cytoskeleton of unmyelinated axons in peripheral nerve during neuropathic hyperalgesia. There was no evidence of unmyelinated fiber loss or a decrease in the number of microtubules per axons. There was, however, a significant decrease in microtubule density in unmyelinated axons from vincristine-treated rats. This decrease in microtubule density was due to a significant increase in the cross-sectional area of unmyelinated axons, suggesting swelling of axons. In addition, vincristine-treated axons had significantly fewer microtubules cut in cross-section and significantly more tangentially oriented microtubules per axon compared to controls. These results suggest that vincristine causes disorganization of the axonal microtubule cytoskeleton, as well as an increase in the caliber of unmyelinated sensory axons.
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PMID:Microtubule disorientation and axonal swelling in unmyelinated sensory axons during vincristine-induced painful neuropathy in rat. 961 1

Although progress in cancer research is paralleled by the discovery and development of novel chemotherapeutic agents, the benefits of these agents are offset by their side-effect profiles. Of the numerous adverse effects associated with antineoplastic drugs, peripheral neuropathy is the most frequent and is often debilitating. This article reviews the treatment options--both primary and secondary--for neuropathic complications of cancer therapy. Before a potentially neurotoxic chemotherapeutic regimen is started, patients should undergo 1) a baseline neurologic history for possible coexisting risk factors for neuropathy; 2) physical evaluation; and 3) if indicated, electrophysiologic testing, including nerve conduction studies and electromyography. Patients should be followed closely for the development of neuropathic signs and symptoms. When symptoms (eg, paresthesias or pain) or deficits (eg, weakness) develop, their severity and their effect on quality of life will determine whether the neurotoxic chemotherapy should be continued at a lower dose or discontinued. Neuropathic pain should be treated aggressively with a stepwise approach. The decision to initiate therapy should be guided first by the severity of pain and second by the convenience of dosing and the side-effect profile of the medication. Specific antineuropathic pain therapy may begin with a tricyclic antidepressant (TCA), titrated to 100 to 150 mg/d, unless anticholinergic side effects appear before this dosage is reached. The TCA may be replaced by or supplemented with antiepileptic agents, such as gabapentin, which is attractive because of its rapid dose titration (maximum, 3600 mg/d) and minimal interaction with other medications. In addition to pharmacologic therapies targeting symptom management, new therapies directed at preventing the onset or progression of neurotoxicity are desperately needed.
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PMID:Neurologic Complications of Cancer Therapy. 1109 27

Neuropathic pain impacts millions of people in the United States and around the world. Patients experience one of many symptoms, such as pain, paresthesia, dysesthesia, hyperalgesia, and allodynia, for many years because of unavailable or inadequate treatment. One of the major challenges in treating patients with neuropathic pain syndromes is a lack of consensus concerning the appropriate first-line treatment options for conditions associated with neuropathic pain, including postherpetic neuralgia, diabetic peripheral neuropathy, and trigeminal neuralgia. This review summarizes the published results of randomized trials involving treatment for neuropathic pain conditions. Anticonvulsants, such as gabapentin, carbamazepine, and lamotrigine, and tricyclic antidepressants, including amitriptyline and desipramine, have demonstrated efficacy in relieving pain associated with postherpetic neuralgia, diabetic peripheral neuropathy, and trigeminal neuralgia, in several studies. However, the lack of head-to-head comparison studies of these agents limits the conclusions that can be reached. Clinicians who must make decisions regarding the care of individual patients may find some guidance from the number of randomized trials with a positive outcome for each agent. Using quality-of-life study outcomes, treatment strategies must encompass the impact of therapeutic agents on the comorbid conditions of sleep disturbance and mood and anxiety disorders associated with neuropathic pain. Looking to the future, emerging therapies, such as pregabalin and newer N-methyl-D-aspartate-receptor blockers, may provide physicians and patients with new treatment options for more effective relief of pain.
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PMID:Pharmacologic management part 1: better-studied neuropathic pain diseases. 1499 28

Neuropathic pain is a clinical entity designating the different types of pain associated with a lesion of the nervous system including a wide range of pathological conditions from painful peripheral lesions (for example diabetic neuropathy, post-zoster pain, trauma-induced nerve injury) and central pain (particularly stroke-induced pain, spinal lesions, and multiple sclerosis). Despite this wide range of etiologies, neuropathic pain has well characterized clinical features which generally allow distinction from other types of pain: continuous often burn-like pain, paroxysmal pain (electrical discharge, knife stab), evoked pain, highly invalidating pain (allodynia, hyperalgesia), and associated dysethesia and/or paresthesia. Over the last ten Years, very little work has been published on neuropathic pain, which is now becoming a very active domain of research in neurobiology. Advances to date have not been spectacular although better tolerated agents have been recently marketed. Future progress should enable an appropriate response to the therapeutic challenge of neuropathic pain.
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PMID:[Neuropathic pain: experimental advances and clinical applications]. 1503 77

Patients with neuropathic pain present a clinical challenge. Neuropathic pain, when chronic, often leads to disability. Diagnosis can be difficult because both positive and negative sensory and motor signs and symptoms may be present, as well as a variety of comorbid conditions. In addition, there may be a high degree of interpatient variability. Currently, clinical evaluation, rather than diagnostic tests, is one of the best available tools for assessment and diagnosis. As with all chronic pain conditions, the key to a thorough assessment is a thorough history that includes medical, functional, and psychosocial evaluations. Currently available pain assessment tools, which are widely used in nursing practice, are still inadequate for use in patients with neuropathic pain. The physical and neurologic examination remains a critical element for patient evaluation. This includes an assessment of spontaneous pain (continuous or intermittent), pain evoked by daily activities (allodynia), and other abnormal sensations that are not necessarily painful (paresthesias, dysesthesias). Sensitivity to pinprick, touch, pressure, cold, heat, and vibration are measured, often confirming the suspected diagnosis. Patients may be confused by the unusual sensations they are experiencing and unable to effectively describe or communicate their symptoms. This communication barrier may contribute to an inadequate physical examination. With improved skills in patient assessment and through enhanced communication with patients, nurses can make an important contribution to treatment outcomes in patients with neuropathic pain.
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PMID:Neuropathic pain: a guide to comprehensive assessment. 1564 55

Neuropathic pain is an increasingly common problem facing the cancer patient. Painful neuropathy can come from various sources and significantly impact quality of life. The most commonly observed scenario is paraesthesia and dysesthesia as a result of toxic effects of chemotherapies on the distal peripheral nerves. Neuropathic pain should be addressed ideally with the help of a neuro-oncologist, and it usually can be successfully treated with a variety of agents, including atypical analgesics such as antidepressants, newer drugs with analgesic benefit, and opioids for more refractory cases. Direct and indirect effects of the primary neoplasm need to be considered in the etiology of specific syndromes of mononeuropathies and plexopathies.
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PMID:Assessment of neuropathic pain in cancer patients. 1958 91

Neuropathic pain syndromes, i.e., pain after a lesion or disease of the peripheral or central nervous system, are clinically characterized by spontaneous pain (ongoing, paroxysms) and evoked types of pain (hyperalgesia, allodynia). A variety of distinct pathophysiological mechanisms in the peripheral and central nervous system operate in concert: In some patients the nerve lesion triggers molecular changes in nociceptive neurons that become abnormally sensitive and develop pathological spontaneous activity (upregulation of sodium channels and receptors, e.g., vanilloid TRPV1 receptors, menthol-sensitive TRPM8 receptors, or alpha-receptors). These phenomena may lead to spontaneous pain, shooting pain sensations, as well as heat hyperalgesia, cold hyperalgesia, and sympathetically maintained pain. Spontaneous activity in damaged large nonnociceptive A-fibers may lead to paresthesias. All these changes may also occur in uninjured neurons driven by substances released by adjacent dying cells and should receive more attention in the future. The hyperactivity in nociceptors in turn induces secondary changes (hyperexcitability) in processing neurons in the spinal cord and brain. This central sensitization causes input from mechanoreceptive A-fibers to be perceived as pain (mechanical allodynia). Neuroplastic changes in the central descending pain modulatory systems (inhibitory or facilitatory) may lead to further hyperexcitability. Neuropathic pain represents a major neurological problem and treatment of patients with such pain has been largely neglected by neurologists in the past. The medical management of neuropathic pain consists of five main classes of oral medication (antidepressants with reuptake blocking effect, anticonvulsants with sodium-blocking action, anticonvulsants with calcium-modulating actions, tramadol, and opioids) and several categories of topical medications for patients with cutaneous allodynia and hyperalgesia (capsaicin and local anesthetics). In many cases an early combination of compounds effecting different mechanisms is useful. At present existing trials only provide general pain relief values for specific causes, which in part may explain the failure to obtain complete pain relief in neuropathic pain conditions. In general, the treatment of neuropathic pain is still unsatisfactorily. Therefore, a new hypothetical concept was proposed in which pain is analyzed on the basis of underlying mechanisms. The increased knowledge of pain-generating mechanisms and their translation into symptoms and signs may in the future allow a dissection of the mechanisms that operate in each patient. If a systematic clinical examination of the neuropathic pain patient and a precise phenotypic characterization is combined with a selection of drugs acting against those particular mechanisms, it should ultimately be possible to design optimal treatments for the individual patient.
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PMID:Neuropathic pain: a clinical perspective. 1965 3

Neuropathic pain is a major health issue and is frequently accompanied by allodynia (painful sensations in response to normally non-painful stimulations), and unpleasant paresthesia/dysesthesia, pointing to alterations in sensory pathways normally dedicated to the processing of non-nociceptive information. Interestingly, mounting evidence indicate that central glial cells are key players in allodynia, partly due to changes in the astrocytic capacity to scavenge extracellular glutamate and gamma-aminobutyric acid (GABA), through changes in their respective transporters (EAAT and GAT). In the present study, we investigated the glial changes occurring in the dorsal column nuclei, the major target of normally innocuous sensory information, in the rat spared nerve injury (SNI) model of neuropathic pain. We report that together with a robust microglial and astrocytic reaction in the ipsilateral gracile nucleus, the GABA transporter GAT-1 is upregulated with no change in GAT-3 or glutamate transporters. Furthermore, [(3)H] GABA reuptake on crude synaptosome preparation shows that transporter activity is functionally increased ipsilaterally in SNI rats. This GAT-1 upregulation appears evenly distributed in the gracile nucleus and colocalizes with astrocytic activation. Neither glial activation nor GAT-1 modulation was detected in the cuneate nucleus. Together, the present results point to GABA transport in the gracile nucleus as a putative therapeutic target against abnormal sensory perceptions related to neuropathic pain.
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PMID:Upregulation of the GABA transporter GAT-1 in the gracile nucleus in the spared nerve injury model of neuropathic pain. 2054 84

Neuropathic pain is defined as 'pain arising as a direct consequence of a lesion or disease of the somatosensory system'. It may reflect a widespread neuropathic process (e.g. diabetic neuropathy) or a more focal disorder (e.g. post-herpetic neuralgia). The practical importance of recognising neuropathic pain (as distinct from nociceptive pain) lies in the difference in effective treatments. The patient may be experiencing more than one type of pain. Many long-term disabling neurological disorders, such as multiple sclerosis, as well as causing neuropathic pain, may also give rise to musculoskeletal pains which may be more readily amenable to treatment. Most treatment for long-term pain, including neuropathic pain, should be provided in primary care, with specialist support. When taking the history it is important to elicit information about the site, duration, intensity and character of the pain, or pains, and what precipitates and relieves it. Accompanying somatosensory disturbance in the painful territory (numbness; allodynia; hyperalgesia; paraesthesia and dysaesthesia) is strongly suggestive of neuropathic pain. A specialist opinion should be sought where the diagnosis is uncertain, or the patient's condition is rapidly deteriorating or uncontrolled. This may be a specialist in a particular condition, to address issues of primary diagnosis, or a specialist in pain medicine to advise on, or provide, further treatment. Patients who are struggling with their pain are best served by specialist centres that can endeavour to explain the condition and encourage self-management.
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PMID:Improving the management of neuropathic pain. 2081 11

Neuropathic pain is a disabling symptom frequently reported by patients with neuropathies. Pain-questionnaires are the best way to investigate it. Neuropathic Pain Symptom Inventory (NPSI) questionnaire specifically assesses the different symptoms of neuropathic pain. The objective of this study was to evaluate, through the NPSI, the different neuropathic painful symptoms in a population of neuropathic patients. 277 patients with different neuropathies were evaluated with the NPSI to investigate the prevalence of the different neuropathic symptoms. Neuropathic pain was reported by 94.4% of the patients, resulting to be common not only in diabetic and iatrogenic neuropathies, but also in hereditary, paraproteinemic, and idiopathic neuropathies. The majority of our patients (88.6%) presented paresthesia/dysesthesia. The results of our study point out the difference in the occurrence of the painful symptoms. A scale able to discriminate distinct types of neuropathic pain may provide clinicians with adequate therapeutic choices in the daily practice.
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PMID:Exploring neuropathic symptoms in a large cohort of Italian patients with different peripheral nervous system diseases. 2136 94


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