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

An aim of the study was to assess effect of duloxetine, a selective inhibitor of serotonin and noradrenalin reuptake, on chronic daily headache (CDH) and its antinociceptive mechanisms. Duloxetine was administered in dosage 60 mg per day during 8 weeks to 40 patients. The high efficacy of the drug by different clinical indices--decrease of days of headache per month, frequency of headache attacks, reduction of analgetics used--was found, all changes being statistically significant. The therapeutic response was developed from the 2nd month of the treatment. The study of the nociceptive flexion reflex revealed the increase of its threshold and of subjective pain threshold as well. Intensity of comorbid disorders, depression and anxiety, was also significantly decreased. Side-effects were small and transient.
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PMID:[Efficacy of duloxetine in the treatment of chronic daily headache]. 1837 68

Thirty-two patients at the acute stage of chronic back pain have been studied. Cymbalta was used as a monotherapy in dosage 60 mg daily during 6 weeks simultaneously with traditional non-pharmacological therapy. Treatment efficacy was assessed using self-rating methods and quantitative scales measuring pain intensity as well as Spilberger trait/state anxiety inventory, Beck depression scale, Plutchik scale measuring psychological defense mechanisms, quality of sleep, quality of life and evaluation of autonomic dysfunction. The treatment with cymbalta resulted in significant reduction of pain in 90% patients, with full stopping of the syndrome in 10% and marked reduction in 55%. The stopping of pain syndrome was correlated with significant improvement of emotional status and quality of life and sleep normalization of the patients.
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PMID:[Treatment of chronic back pain with antidepressant cymbalta: an experimental study]. 1837 77

The primary objectives of this study were to assess the efficacy and safety of duloxetine for reducing pain severity in fibromyalgia patients with or without current major depressive disorder. This was a 6-month, multicenter, randomized, double-blind, placebo-controlled study. In total, 520 patients meeting American College of Rheumatology criteria for fibromyalgia were randomly assigned to duloxetine (20 mg/day, 60 mg/day, or 120 mg/day) or placebo, administered once daily, for 6 months (after 3 months, the duloxetine 20-mg/day group titrated to 60 mg/day). The co-primary outcome measures were the Brief Pain Inventory (BPI) average pain severity score and Patient Global Impressions of Improvement (PGI-I) score. Safety was assessed via treatment-emergent adverse events, and changes in vital sign, laboratory, and ECG measures. Compared with placebo-treated patients, those patients treated with duloxetine 120 mg/day improved significantly more on the co-primary outcome measures at 3 months (change in BPI score [-2.31 vs -1.39, P<0.001] and PGI-I [2.89 vs 3.39, P=0.004]) and at 6 months (change in BPI [-2.26 vs -1.43, P=0.003] and PGI-I [2.93 vs 3.37, P=0.012]). Compared with placebo, treatment with duloxetine 60 mg/day also significantly improved the co-primary measures at 3 months and BPI at 6 months. Duloxetine was efficacious in patients both with and without major depressive disorder. There were no clinically significant differences between treatment groups in changes in vital signs, laboratory measures, or ECG measures. Study results demonstrated that duloxetine at doses of 60 mg/day and 120 mg/day appears to be safe and efficacious in patients with fibromyalgia.
Pain 2008 Jun
PMID:Efficacy and safety of duloxetine for treatment of fibromyalgia in patients with or without major depressive disorder: Results from a 6-month, randomized, double-blind, placebo-controlled, fixed-dose trial. 1898 1

L5/L6 spinal nerve ligation (SNL) in rodents induces behavioral signs similar to the symptoms of neuropathic pain in humans. L5/L6 SNL in rats has been well characterized so far, but there have been few studies using mice. In this study, we established an L5/L6 SNL model in mice and examined the effects of known antinociceptive drugs in the model. We also analyzed the changes in gene expression in dorsal root ganglions with special reference to those which are known to change in a neuropathic pain state to validate the model. Mechanical allodynia in the ipsilateral side paw was observed beginning on day 1 and lasted for at least 2 months following surgery. Diclofenac showed no significant effect on the mechanical allodynia. Gabapentin and pregabalin completely reversed allodynia, but they also caused a decrease in locomotor activity. Duloxetine caused a partial recovery of the threshold. Mexiletine completely reversed allodynia, but it also caused sedation or motor impairment. Morphine caused a partial recovery of the threshold and hyper-locomotion. This mouse L5/L6 SNL model represents a robust mechanical allodynia, which shows a similar pharmacological response to that reported in rats and human patients with neuropathic pain. The pattern changes in gene expression also resembled those reported in rats. This model will therefore be useful for investigation of the effects of novel antinociceptive compounds and the mechanisms of neuropathic pain.
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PMID:Pharmacological characterization and gene expression profiling of an L5/L6 spinal nerve ligation model for neuropathic pain in mice. 1840 Apr 11

Major depressive disorder (MDD) is one of the most disabling disorders. Antidepressant pharmacotherapy is currently effective in approximately 70% of all treated cases; the potential superiority of a dual mechanism of pharmacological action (e.g., inhibiting the reuptake of serotonin and norepinephrine) is widely known. Duloxetine, a novel dual acting, selective serotonin and norepinephrine reuptake inhibitor, has demonstrated clinical efficacy in the treatment of MDD and general anxiety disorder (GAD). Duloxetine has been found to be safe and well tolerated, with mild-to-moderate adverse events, a favorable cardiovascular and sexual dysfunction profile, and minor influence on weight gain. The efficacy of duloxetine in the treatment of MDD has been established in randomized, double-blind, placebo-controlled studies. In addition to improving classical emotional symptoms of MDD, duloxetine has in particular beneficial effects on somatic symptoms of depression including pain. The superiority of duloxetine was shown over placebo, while comparison studies with other antidepressants showed only partial superiority. Randomized clinical trials in GAD also provide evidence for beneficial effects compared with placebo and improvement in quality of life, wellbeing and general health. Moreover, duloxetine is effective and well tolerated in the treatment of diabetic peripheral neuropathic pain and stress urinary incontinence. First results indicate that duloxetine might also be effective in the treatment of children with depression and pain. Overall, duloxetine is an interesting novel treatment option in the management of major depression and has shown efficacy in a broad range of diseases. It therefore may provide additional benefit to current therapeutic options in the treatment of psychiatric, internal, as well as urological disorders such as spinal dysfunctions. Due to duloxetine's properties, a wide range of use will be encountered in the mid-to-long term.
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PMID:Duloxetine in the treatment of major psychiatric and neuropathic disorders. 1841 56

Although sleep problems are common in patients with chronic pain, it is unclear whether pain mediates (causes) impaired sleep. The relationship between pain and sleep has been difficult to investigate because of the potential confounds of depression and somnolence. This report used clinical trials data for duloxetine in the management of diabetic peripheral neuropathic pain (DPNP) to investigate the direction of this association. Data were pooled from three double-blind, randomized, placebo-controlled, 12-week trials of patients with DPNP without mood disorder (n=1,139). DPNP patients reporting somnolence and those who were receiving sedating concomitant medications were removed from the analyses (n=93). Efficacy measures included weekly mean scores for average daily pain severity, night pain severity, and pain interference with sleep. Duloxetine at 60 and 120 mg per day separated from placebo for average pain and night pain improvement as early as one week after treatment began, whereas sleep interference improvement separated from placebo at the three visits it was assessed (Weeks 4, 8, and 12). Change in sleep interference was moderately to strongly correlated (P<0.001) with changes in average pain (r=0.46) and nighttime pain severity (r=0.53). These results confirm the association between the improvement in daily pain and nighttime pain, and improvement in sleep interference for a large population without depression or somnolence. Although this association cannot establish causality, these results provide some evidence for the possibility that pain may mediate the sleep problem associated with DPNP and perhaps chronic pain in general.
J Pain Symptom Manage 2008 Dec
PMID:Does pain mediate the pain interference with sleep problem in chronic pain? Findings from studies for management of diabetic peripheral neuropathic pain with duloxetine. 1850 92

We previously reported that gabapentin activates the bulbospinal-spinal noradrenergic-cholinergic pathway to produce analgesia in rats after nerve injury. Also, gabapentin interacts synergistically with a cholinesterase inhibitor donepezil to produce analgesia. Duloxetine, a serotonin/noradrenaline re-uptake inhibitor, has been used for the treatment of neuropathic pain and should amplify the noradrenergic mechanisms recruited by gabapentin. In the present study, we determined the interaction between duloxetine and gabapentin with and without donepezil when administered by the clinically preferred oral route in rats after spinal nerve ligation. The ED(50) value of gabapentin, donepezil, and duloxetine to reduce mechanical hypersensitivity after nerve injury was 45, 3.7, and 32 mg/kg, respectively. In the examination of two drug combinations, oral duloxetine with either gabapentin or donepezil were additive to reduce hypersensitivity. The combination of all three drugs yielded a synergistic interaction with an observed ED(50) at 1/4th the predicted dose of additivity, likely due to the gabapentin-donepezil interaction. This three drug combination did not affect motor coordination or show signs of sedation in the rotarod test. Analgesia by the combination of these three drugs was reversed by intrathecal injection either of the alpha(2)-adrenoceptor antagonist idazoxan or by the muscarinic receptor antagonist atropine. These results suggest that the combination of these drugs, which stimulate and augment the bulbospinal-spinal noradrenergic-cholinergic pathway, lowers the dose requirement for each drug to reduce hypersensitivity after nerve injury without sedative effects. The current study provides the rationale for clinical study of the combination of gabapentin, donepezil and duloxetine to treat neuropathic pain.
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PMID:Multiplicative interactions to enhance gabapentin to treat neuropathic pain. 1882 81

Fibromyalgia syndrome (FMS) is a chronic condition characterized by widespread pain, tender points, fatigue, and sleep disturbance. FMS leads to high disability levels, poor quality of life, and extensive use of medical care. Effective pharmacological treatment options are rare, and treatment effects are often of limited duration. Duloxetine is a new selective serotonin and norepinephrine reuptake inhibitor that is licensed for the treatment of pain in diabetic neuropathy. So far two randomized, placebo-controlled trials have investigated the short-term safety and efficacy of duloxetine 60 mg/day and 120 mg/day in patients suffering from FMS over a period of 12 weeks. Both dosages were superior to placebo in pain relief, and improvement in quality of life and depressive symptoms. The analgesic effect was largely independent of the antidepressant action of duloxetine. The higher dose of 120 mg/day further reduced the tender point count and elevated the tender point pain thresholds. Only mild to moderate adverse effects were reported. Duloxetine 60 mg/day and 120 mg/day has proven to be beneficial in the treatment of FMS symptoms. As true for other antidepressants further studies are needed to assess the long-term efficacy and safety of duloxetine as an additional pharmacological treatment option in FMS.
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PMID:New treatment options for fibromyalgia: critical appraisal of duloxetine. 1883 Mar 99

The underlying cause of fibromyalgia is not known, although dysfunction of serotoninergic and noradrenergic neurotransmitters appears to play an important role in the condition. Duloxetine is a newer and better tolerated dual antidepressant that does not induce muscarinic, histaminergic or adrenergic adverse reactions, and at the same time modulates and enhances the endogenous descending system that inhibits nociception. Duloxetine reduces pain symptoms in depression and other diseases and conditions, including fibromyalgia. Over 90% of the observed effect on pain is due to a direct analgesic effect rather than an indirect antidepressant effect. In clinical trials, pain reduction with duloxetine was not associated with its antidepressant and anxiolytic effects in patients with fybromialgia. A meta-analysis of four randomized, double-blind, placebo-controlled studies of duloxetine in the treatment of fibromyalgia showed it to be significantly superior to placebo in providing pain relief, reducing fatigue and improving physical and mental performance. The results of safety studies indicate that duloxetine is safe and well tolerated. Adverse effects tend to be mild, appearing more often at the start of therapy and decreasing or disappearing over the course of continued treatment.
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PMID:Duloxetine for the treatment of fibromyalgia. 1913 26

Duloxetine is a selective serotonin and norepinephrine reuptake inhibitor available in delayed-release capsules for oral use. Duloxetine 60 mg/day, compared with placebo, was associated with a greater reduction from baseline in the Brief Pain Inventory (BPI) average pain severity score, a greater improvement in the patient-rated global impression of improvement (PGI-I) scale in patients with fibromyalgia, with or without major depressive disorder, in two 12- and 15-week phase III studies. In a 27-week, phase III trial, there was no significant difference between duloxetine (60 or 120 mg/day) and placebo for the least squares mean change from baseline to endpoint in BPI average pain scores and the PGI-I score. The significant improvements in efficacy that occurred in patients with fibromyalgia during 8 weeks of open-label treatment with duloxetine 60 mg/day were generally maintained during 52 weeks of subsequent blinded treatment at the same dosage in a phase III trial. Nonresponders during treatment with open-label duloxetine 60 mg/day, demonstrated no increased ability to respond if the duloxetine dosage was up-titrated to 120 mg/day than those who remained on the same dosage during the subsequent 52-week, double-blind phase. Duloxetine was generally well tolerated in studies of up to 1 year in duration, with nausea being the most frequent adverse event and main cause for discontinuing therapy.
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PMID:Duloxetine: in patients with fibromyalgia. 1953 38


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