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 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There is abundant evidence that extracellular ATP and other nucleotides have an important role in pain signaling at both the periphery and in the CNS. At first, it was thought that ATP was simply involved in acute pain, since ATP is released from damaged cells and excites directly primary sensory neurons by activating their receptors. However, neither blocking P2X/Y receptors pharmacologically nor suppressing the expression of P2X/Y receptors molecularly in sensory neurons or in the spinal cord had an effect on acute physiological pain. The focus of attention now is on the possibility that endogenous ATP and its receptor system might be activated in pathological pain states, particularly in 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; unfortunately, this state is generally resistant to currently available treatments. An important advance in our understanding of the mechanisms involved in neuropathic pain has been made by a recent work demonstrating the crucial role of ATP receptors (i.e., P2X(3) and P2X(4) receptors). In this review, we summarize the role of ATP receptors, particularly the P2X(4) receptor, in neuropathic pain. The expression of P2X(4) receptors in the spinal cord is enhanced in spinal microglia after peripheral nerve injury, and blocking pharmacologically and suppressing molecularly P2X(4) receptors produce a reduction of the neuropathic pain behaviour. Understanding the key roles of ATP receptors including P2X(4) receptors may lead to new strategies for the management of neuropathic pain.
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PMID:ATP receptors in pain sensation: Involvement of spinal microglia and P2X(4) receptors. 1840 95

Small fibre neuropathy (SFN), a condition dominated by neuropathic pain, is frequently encountered in clinical practise either as prevalent manifestation of more diffuse neuropathy or distinct nosologic entity. Aetiology of SFN includes pre-diabetes status and immune-mediated diseases, though it remains frequently unknown. Due to their physiologic characteristics, small nerve fibres cannot be investigated by routine electrophysiological tests, making the diagnosis particularly difficult. Quantitative sensory testing (QST) to assess the psychophysical thresholds for cold and warm sensations and skin biopsy with quantification of somatic intraepidermal nerve fibres (IENF) have been used to determine the damage to small nerve fibres. Nevertheless, the diagnostic criteria for SFN have not been defined yet and a 'gold standard' for clinical practise and research is not available. We screened 486 patients referred to our institutions and collected 124 patients with sensory neuropathy. Among them, we identified 67 patients with pure SFN using a new diagnostic 'gold standard', based on the presence of at least two abnormal results at clinical, QST and skin biopsy examination. The diagnosis of SFN was achieved by abnormal clinical and skin biopsy findings in 43.3% of patients, abnormal skin biopsy and QST findings in 37.3% of patients, abnormal clinical and QST findings in 11.9% of patients, whereas 7.5% patients had abnormal results at all the examinations. Skin biopsy showed a diagnostic efficiency of 88.4%, clinical examination of 54.6% and QST of 46.9%. Receiver operating characteristic curve analysis confirmed the significantly higher performance of skin biopsy comparing with QST. However, we found a significant inverse correlation between IENF density and both cold and warm thresholds at the leg. Clinical examination revealed pinprick and thermal hypoesthesia in about 50% patients, and signs of peripheral vascular autonomic dysfunction in about 70% of patients. Spontaneous pain dominated the clinical picture in most SFN patients. Neuropathic pain intensity was more severe in patients with SFN than in patients with large or mixed fibre neuropathy, but there was no significant correlation with IENF density. The aetiology of SFN was initially unknown in 41.8% of patients and at 2-year follow-up a potential cause could be determined in 25% of them. Over the same period, 13% of SFN patients showed the involvement of large nerve fibres, whereas in 45.6% of them the clinical picture did not change. Spontaneous remission of neuropathic pain occurred in 10.9% of SFN patients, while it worsened in 30.4% of them.
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PMID:The diagnostic criteria for small fibre neuropathy: from symptoms to neuropathology. 1883 4

Neuropathic pain is characterized by a heavier intensity and a longer duration than in non-neuropathic chronic pain. Its frequency is estimated around 9% of the population aged 65 years and over. Diabetes, shingles, cancer, surgery, radiculopathies or stroke are frequent in elderly and may lead to neuropathic pain. It's treatment is a real challenge in elderly. Beside the difficulties of pain evaluation and choice of a therapeutic strategy, intercurrent diseases associated with aging and polymedication require a complex drug treatment. The leading role of cognition, emotion, physical activity for autonomy preservation, and the dynamic interaction between these domains in the old, oldest old and most fragile persons, imply that any pharmacological treatment must be integrated into a non-pharmacological approach. However, very few studies has been specifically devoted to neuropathic pain in elderly. Epidemiological studies and controlled clinical trials are necessary to optimize pain treatment and could result in polymodal therapeutic strategies, which until now only are evidence-based or intuitively developed.
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PMID:[Neuropathic pain in the elderly]. 1855 69

In contrast to physiological pain, pathological pain is not dependent on the presence of tissue-damaging stimuli. One type of pathological pain--neuropathic pain--is often a consequence of nerve injury or of diseases such as diabetes, AIDS, or cancer. Neuropathic pain can be agonizing, can persist over long periods, and, unfortunately, is often resistant to known painkillers. There is a rapidly growing body of evidence indicating that microglia, the CNS immune cells, have causal roles in the pathogenesis of pain hypersensitivity following nerve injury. We will review recent advances in our understanding of the mechanisms producing neuropathic pain, focusing on the roles of microglia-expressed molecules, including cell surface receptors, intracellular signaling molecules, and diffusible factors involved in nerve injury-induced pain behaviors and hyperexcitability of dorsal horn neurons. Elucidating how spinal microglia cause neuropathic pain may provide us with exciting insights into pain mechanisms and clues for developing new drugs for the treatment of neuropathic pain.
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PMID:Microglia and neuropathic pain. 1930 58

Neuropathic pain (NP) is defined as pain caused by lesion or dysfunction of the somatosensory system, as a result of abnormal activation of the nociceptive pathway (small fibers and spinothalamic tracts). The most common causes of this syndrome are the following: diabetes, post-herpetic neuralgia, trigeminal neuralgia, stroke, multiple sclerosis, spinal cord injury, HIV infection, cancer. In the last few years, the NP has been receiving special attention for two main reasons: (1) therapeutical refractoriness of a variety of pain syndromes with predominant neuropathic characteristics and (2) the development of diagnostic tools for neuropathic pain complaints. The present review article provides relevant information on the understanding and recognition of NP, as well as evidence-based therapeutic approaches.
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PMID:What do general neurologists need to know about neuropathic pain? 1972 68

Neuropathic pain is a debilitating form of chronic pain resulting from nerve injury, disease states, or toxic insults. Neuropathic pain is often refractory to conventional pharmacotherapies, necessitating validation of novel analgesics. Cannabinoids, drugs that share the same target as Delta(9)-tetrahydrocannabinol (Delta(9)-THC), the psychoactive ingredient in cannabis, have the potential to address this unmet need. Here, we review studies evaluating cannabinoids for neuropathic pain management in the clinical and preclinical literature. Neuropathic pain associated with nerve injury, diabetes, chemotherapeutic treatment, human immunodeficiency virus, multiple sclerosis, and herpes zoster infection is considered. In animals, cannabinoids attenuate neuropathic nociception produced by traumatic nerve injury, disease, and toxic insults. Effects of mixed cannabinoid CB(1)/CB(2) agonists, CB(2) selective agonists, and modulators of the endocannabinoid system (i.e., inhibitors of transport or degradation) are compared. Effects of genetic disruption of cannabinoid receptors or enzymes controlling endocannabinoid degradation on neuropathic nociception are described. Specific forms of allodynia and hyperalgesia modulated by cannabinoids are also considered. In humans, effects of smoked marijuana, synthetic Delta(9)-THC analogs (e.g., Marinol, Cesamet) and medicinal cannabis preparations containing both Delta(9)-THC and cannabidiol (e.g., Sativex, Cannador) in neuropathic pain states are reviewed. Clinical studies largely affirm that neuropathic pain patients derive benefits from cannabinoid treatment. Subjective (i.e., rating scales) and objective (i.e., stimulus-evoked) measures of pain and quality of life are considered. Finally, limitations of cannabinoid pharmacotherapies are discussed together with directions for future research.
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PMID:Cannabinoids as pharmacotherapies for neuropathic pain: from the bench to the bedside. 1978 75

Neuropathic pain refers to pain that originates from pathology of the nervous system. Diabetes, infection (herpes zoster), nerve compression, nerve trauma, and autoimmune diseases are examples of diseases that may cause neuropathic pain. Unfortunately no satisfactory treatment is yet available for this type of pain. This consideration has led to an explosion of interest for the underlying mechanisms, accompanied by a growing number of animal models. In recent years, most of the neuropathic pain models initially developed in the rat have been translated to mice in order to exploit the resource represented by genetically modified mice. Obviously the most useful animal models of pain would be ones in which the etiology of the pain would be endogenous and not induced by the experimenters: together with the classic models based on peripheral nerve ligation, in the last years other techniques are being developed that mimic more closely clinical pain syndromes, often by attempting to induce the disease associated to neuropathic pain. Although several variables must be taken into account when using animal models for mimicking clinical neuropathic pain, the huge number of models that are now reproducible and well characterized should help to reach important goals in the comprehension of mechanisms and to discover novel therapeutic target for this disease.
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PMID:Murine models of human neuropathic pain. 1987 43

Neuropathic pain refers to pain that originates from pathology of the nervous system. Common causes of neuropathic pain are diabetes mellitus, reactivation of herpes zoster, nerve compression or radiculopathy, alcohol, chemotherapy or abuse of some drugs, and trigeminal neuralgia. Specific symptoms of neuropathic pain are mechanical allodynia and cold hyperalgesia. Drugs to treat neuropathic pain can be divided into adjuvant analgesics (antidepressants and anticonvulsants), opioids and topical agents. The use of multiple drug therapies is common in practice. Despite considerable increase in the number of randomized placebo-controlled trials in neuropathic pain in the last few years, the medical treatment of neuropathic pain is still far from being satisfactory, with less than half of patients achieving significant benefit with any pharmacological drug.
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PMID:Neuropathic pain. 2005 64

Neuropathy is one of the many complications of diabetes mellitus, along with micro- and macroangiopathy. Chronic sensorimotor distal symmetric polyneuropathy is the most common form between neuropathies; more than 30% of the diabetic patients are affected by this complication. Treatment is based on three cornerstones: (1) multifactorial intervention aimed at normoglycemia; (2) drugs that target pathogenic mechanisms and (3) symptomatic treatment. Among pathogenic treatments, alpha-lipoic acid and benfotiamine are available in several countries. Neuropathic pain, which affects 8-26% of diabetic patients, exerts a substantial impact on the quality of life. Among the centrally acting analgesic drugs, tricyclic antidepressants, carbamazepine, gabapentin and opioids have been mainly used to treat neuropathic pain. More recently, significant pain relief has been reported using agents such as duloxetine, a dual selective serotonin noradrenaline reuptake inhibitor, and pregabalin, an anticonvulsant, a specific modulator of the alpha2delta subunit of the voltage-dependent calcium channels. Until now, at least 50 new molecular entities have reached clinical stage of development. Strategies that may show promise over existing treatments include topical therapies, analgesic combinations and, in future, gene-related therapies.
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PMID:[Pharmacologic therapy in peripheral diabetic polyneuropathy]. 2070 Sep 63

Neuropathic pain is a common diabetic complication affecting 8-16% of diabetic patients. It is characterized by aberrant symptoms of spontaneous and stimulus-evoked pain including hyperalgesia and allodynia. Magnesium (Mg) deficiency has been proposed as a factor in the pathogenesis of diabetes-related complications, including neuropathy. In the central nervous system, Mg is also a voltage-dependent blocker of the N-methyl-d-aspartate receptor channels involved in abnormal processing of sensory information. We hypothesized that Mg deficiency might contribute to the development of neuropathic pain and the worsening of clinical and biological signs of diabetes and consequently, that Mg administration could prevent or improve its complications. We examined the effects of oral Mg supplementation (296 mg l(-1) in drinking water for 3 weeks) on the development of neuropathic pain and on biological and clinical parameters of diabetes in streptozocin (STZ)-induced diabetic rats. STZ administration induced typical symptoms of type 1 diabetes. The diabetic rats also displayed mechanical hypersensitivity and tactile and thermal allodynia. The level of phosphorylated NMDA receptor NR1 subunit (pNR1) was higher in the spinal dorsal horn of diabetic hyperalgesic/allodynic rats. Magnesium supplementation failed to reduce hyperglycaemia, polyphagia and hypermagnesiuria, or to restore intracellular Mg levels and body growth, but increased insulinaemia and reduced polydipsia. Moreover, it abolished thermal and tactile allodynia, delayed the development of mechanical hypersensitivity, and prevented the increase in spinal cord dorsal horn pNR1. Thus, neuropathic pain symptoms can be attenuated by targeting the Mg-mediated blockade of NMDA receptors, offering new therapeutic opportunities for the management of chronic neuropathic pain.
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PMID:Magnesium attenuates chronic hypersensitivity and spinal cord NMDA receptor phosphorylation in a rat model of diabetic neuropathic pain. 2083 44


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