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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, a form of chronic pain caused by injury to or disease of the peripheral or central nervous system, is a formidable therapeutic challenge to clinicians because it does not respond well to traditional pain therapies. Our knowledge about the pathogenesis of neuropathic pain has grown significantly over last 2 decades. Basic research with animal and human models of neuropathic pain has shown that a number of pathophysiological and biochemical changes take place in the nervous system as a result of an insult. This property of the nervous system to adapt morphologically and functionally to external stimuli is known as neuroplasticity and plays a crucial role in the onset and maintenance of pain symptoms. Many similarities between the pathophysiological phenomena observed in some epilepsy models and in neuropathic pain models justify the rational for use of anticonvulsant drugs in the symptomatic management of neuropathic pain disorders. Carbamazepine, the first anticonvulsant studied in clinical trials, probably alleviates pain by decreasing conductance in Na+ channels and inhibiting ectopic discharges. Results from clinical trials have been positive in the treatment of trigeminal neuralgia, painful diabetic neuropathy and postherpetic neuralgia. The availability of newer anticonvulsants tested in higher quality clinical trials has marked a new era in the treatment of neuropathic pain. Gabapentin has the most clearly demonstrated analgesic effect for the treatment of neuropathic pain, specifically for treatment of painful diabetic neuropathy and postherpetic neuralgia. Based on the positive results of these studies and its favourable adverse effect profile, gabapentin should be considered the first choice of therapy for neuropathic pain. Evidence for the efficacy of phenytoin as an antinociceptive agent is, at best, weak to modest. Lamotrigine has good potential to modulate and control neuropathic pain, as shown in 2 controlled clinical trials, although another randomised trial showed no effect. There is potential for phenobarbital, clonazepam, valproic acid, topiramate, pregabalin and tiagabine to have antihyperalgesic and antinociceptive activities based on result in animal models of neuropathic pain, but the efficacy of these drugs in the treatment of human neuropathic pain has not yet been fully determined in clinical trials. The role of anticonvulsant drugs in the treatment of neuropathic pain is evolving and has been clearly demonstrated with gabapentin and carbamazepine. Further advances in our understanding of the mechanisms underlying neuropathic pain syndromes and well-designed clinical trials should further the opportunities to establish the role of anticonvulsants in the treatment of neuropathic pain.
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PMID:Anticonvulsants for neuropathic pain syndromes: mechanisms of action and place in therapy. 1112 21

Neuropathic pain, a persistent chronic pain resulting from damage to the central or peripheral pain signaling pathway, has become an area of intense research activity--largely because it represents a disorder with high unmet medical need. It is not a single disease entity, but rather includes a range of heterogeneous conditions that differ in etiology, location and initiating cause. Despite this diversity, the clinical presentation is frequently surprisingly similar, which suggests a common biological basis. Until recently, little was known of the mechanisms underlying the various neuropathic pain conditions, making the directed development of novel therapies almost impossible. However, the steady increase in our understanding of the anatomical, cellular and molecular basis of neuropathic pain, coupled with the advent of a number of experimental models of neuropathy, has permitted relatively rapid progress, and the prospects for the emergence of new, more effective therapies look very good. Gabapentin (Pfizer), which appears to act by blocking calcium channels, is the first drug to acquire widespread regulatory approval for the treatment of neuropathic pain. The Society for Medicines Research symposium held June 26, 2003, considered this treatment modality alongside other approaches to therapy, such as N-methyl-D-aspartate receptor antagonists and cannabinoid receptor agonists. The whole meeting provided an excellent description of the challenges facing neuropathic pain drug discovery--at both the research and the development phases of the value chain.
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PMID:Pharmacotherapy for neuropathic pain: progress and prospects. 1470 44

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

The purpose of this study was to assess the possible synergistic interaction between gabapentin and B-vitamins (100:100:1 of vitamin B1, B6 and B12, respectively) in a neuropathic pain model in the rat. Neuropathic pain was induced by ligation of the left L5 and L6 spinal nerves of female Wistar rats. Tactile allodynia was determined by measuring paw withdrawal in response to probing with a series of calibrated von Frey filaments. Gabapentin (30-300 mg/kg), B-vitamins (75-600 mg/kg), or a combination of gabapentin and B-vitamins were administered orally and the antiallodynic effect was determined. Isobolographic analyses were used to define the nature of the functional interactions between gabapentin and B-vitamins in a fixed-dose ratio (0.5:0.5). Gabapentin (ED30 23.0+/-5.3 mg/kg), B-vitamins (ED30 524.0+/-97.0 mg/kg), or a fixed-dose ratio combination of gabapentin-B vitamins combinations dose-dependently reduced tactile allodynia. The theoretical ED30 value for the combination estimated from the isobologram was 273.5+/-48.6 mg/kg. This value was significantly higher than the experimental ED30 value which was 18.7+/-1.7 mg/kg. Results indicate that systemic administration of gabapentin and B vitamins can interact synergistically to reduce neuropathic pain in the rat and suggest the use of this combination to relieve neuropathy in humans.
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PMID:Oral administration of B vitamins increases the antiallodynic effect of gabapentin in the rat. 1563 18

Neuropathic pain and paroxysmal symptoms are common in multiple sclerosis (MS) patients, although no double-blind clinical trial has been conducted to support antiepileptic medications (AED) use in MS. The aim of the study was to evaluate the frequency of AED utilisation and reported adverse events, in a cohort of MS patients. For a period of 3 years the rationale for prescribing AED, adverse effects, treatment duration and reasons for discontinuation were recorded in a database. Carbamazepine (CBZ) was prescribed in 36 patients, with adverse effects reported in 20 cases, of which 12 mimicked a relapse. Gabapentin (GBP) was prescribed in 94 patients, with adverse effects reported in 16 cases and in one case mimicked a relapse. Lamotrigine (LMT) was prescribed in 22 patients, with adverse effects reported in 4 cases, none mimicking a relapse. The present study found a significantly higher incidence of adverse effects in patients treated with CBZ, with a high rate of discontinuation at low dosages and episodes of evident worsening of neurological functioning compared to GBP or LMT.
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PMID:Antiepileptic medications in multiple sclerosis: adverse effects in a three-year follow-up study. 1572 92

Neuropathic pain is a clinical manifestation characterized by the presence of spontaneous pain, allodynia and hyperalgesia. Here, we have evaluated the involvement of CB1 cannabinoid receptors in the development and expression of neuropathic pain. For this purpose, partial ligation of the sciatic nerve was performed in CB1 cannabinoid receptor knockout mice and their wild-type littermates. The development of mechanical and thermal allodynia, and thermal hyperalgesia was evaluated by using the von Frey filaments, cold-plate and plantar tests, respectively. Pre-surgical tactile and thermal withdrawal thresholds were similar in both genotypes. In wild-type mice, sciatic nerve injury led to a neuropathic pain syndrome characterized by a marked and long-lasting reduction of the paw withdrawal thresholds to mechanical and thermal stimuli. These manifestations developed similarly in mice lacking CB1 cannabinoid receptors. We have also investigated the consequences of gabapentin administration in these animals. Gabapentin (50 mg/kg/day, i.p.) induced a similar suppression of mechanical and thermal allodynia in both wild-type and CB1 knockout mice. Mild differences between genotypes were observed concerning the effect of gabapentin in the expression of thermal hyperalgesia. Taken together, our results indicate that CB1 cannabinoid receptors are not critically implicated in the development of neuropathic pain nor in the anti-allodynic and anti-hyperalgesic effects of gabapentin in this model.
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PMID:Development and expression of neuropathic pain in CB1 knockout mice. 1616 63

Neuropathic pain is a common and potentially treatable cause of considerable lifelong morbidity. Effective pharmacological treatments are scarce, but one group of drugs that has shown promise is the antiepileptics. Gabapentin has become popular as a first-line treatment for neuropathic pain because of its efficacy as an antineuropathic agent and relatively benign side-effect profile. However, its mechanism of action is far from clear. This review discusses the available evidence for the postulated mechanisms of action of gabapentin. Understanding the mechanism of action of this agent may well lead to the development of safer and more effective antineuropathic drugs.
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PMID:The mechanism of action of gabapentin in neuropathic pain. 1642 69

Neuropathic pain is a debilitating condition affecting millions of people around the world and is defined as pain that follows a lesion or dysfunction of the nervous system. This type of pain is difficult to treat, but the novel compounds pregabalin (Lyrica) and gabapentin (Neurontin) have proven clinical efficacy. Unlike traditional analgesics such as nonsteroidal antiinflammatory drugs or narcotics, these agents have no frank antiinflammatory actions and no effect on physiological pain. Although extensive preclinical studies have led to a number of suggestions, until recently their mechanism of action has not been clearly defined. Here, we describe studies on the analgesic effects of pregabalin in a mutant mouse containing a single-point mutation within the gene encoding a specific auxiliary subunit protein (alpha2-delta-1) of voltage-dependent calcium channels. The mice demonstrate normal pain phenotypes and typical responses to other analgesic drugs. We show that the mutation leads to a significant reduction in the binding affinity of pregabalin in the brain and spinal cord and the loss of its analgesic efficacy. These studies show conclusively that the analgesic actions of pregabalin are mediated through the alpha2-delta-1 subunit of voltage-gated calcium channels and establish this subunit as a therapeutic target for pain control.
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PMID:Identification of the alpha2-delta-1 subunit of voltage-dependent calcium channels as a molecular target for pain mediating the analgesic actions of pregabalin. 1708 53

Neuropathic pain is defined as pain caused by a lesion in the nervous system and is common in clinical practice. Diagnosis can be difficult. Recommendations for first-line pharmacologic treatments are based on positive results from multiple, randomized, controlled trials, and recommendations for second-line pharmacologic treatments are based on the positive result of a single, randomized, controlled trial or inconsistent results of multiple, randomized, controlled trials. The results of published trials and clinical experience provide the foundation for specific recommendations for first-line treatments, which include gabapentin, 5% lidocaine patch, opioid analgesics, tramadol hydrochloride, and tricyclic antidepressants (TCAs). Gabapentin (up to 3,600 mg/day) significantly reduced pain compared with placebo; improvements in sleep, mood, and quality of life were also demonstrated. Adverse effects of gabapentin include somnolence and dizziness, and, less commonly, gastrointestinal symptoms and mild peripheral edema. Thus, monitoring and dosage adjustment are required, without discontinuation of the drug. Gabapentin combined with morphine achieved better analgesia at lower doses of each drug than each drug alone, with only mild adverse effects. The first medication that proved effective for neuropathic pain in placebo-controlled trials was TCAs. Treatment decisions for patients with neuropathic pain can be difficult. Interest in the mechanisms and treatment of chronic neuropathic pain has increased during the past years, resulting in significant treatment advances in the future. In this article all recent knowledge on therapeutic management of chronic neuropathic pain is presented.
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PMID:Therapeutic management of chronic neuropathic pain: an examination of pharmacologic treatment. 1719 64

Spinal cord injury (SCI) has a number of severe and disabling consequences, including chronic pain, and around 40% of patients develop persistent neuropathic pain. Pain following SCI has a detrimental impact on the patient's quality of life and is a major specific healthcare problem in its own right. Thus far, there is no cure for the pain and oral pharmaceutical intervention is often inadequate, commonly resulting in a reduction of only 20-30% in pain intensity. Neuropathic pain sensations are characterized by spontaneous persistent pain and a range of abnormally evoked responses, e.g. allodynia (pain evoked by normally non-noxious stimuli) and hyperalgesia (an increased response to noxious stimuli). Neuropathic pain following SCI may be present at or below the level of injury. Oral pharmacological agents used in the treatment of neuropathic pain act either by depressing neuronal activity, by blocking sodium channels or inhibiting calcium channels, by increasing inhibition via GABA agonists, by serotonergic and noradrenergic reuptake inhibition, or by decreasing activation via glutamate receptor inhibition, especially by blocking the NMDA receptor. At present, only ten randomized, double-blind, controlled trials have been performed on oral drug treatment of pain after SCI, the results of most of which were negative. The studies included antidepressants (amitriptyline and trazodone), antiepileptics (gabapentin, pregabalin, lamotrigine and valproate) and mexiletine. Gabapentin, pregabalin and amitriptyline showed a significant reduction in neuropathic pain following SCI. Cannabinoids have been found to relieve other types of central pain, and serotonin noradrenaline reuptake inhibitors as well as opioids relieve peripheral neuropathic pain and may be used to treat patients with SCI pain.
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PMID:Pharmacological management of neuropathic pain following spinal cord injury. 1848 90


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