IntroductionFibromyalgia is a chronic disorder characterized by widespread pain and tenderness. Prior trials have demonstrated the efficacy of pregabalin for the relief of fibromyalgia symptoms, and it is approved for the treatment of fibromyalgia in the United States. However, prior to this study, there has not been a large-scale efficacy trial in patients with fibromyalgia in Japan.MethodsThis randomized, double-blind, multicenter, placebo-controlled trial was conducted at 44 centers in Japan to assess the efficacy and safety of pregabalin for the symptomatic relief of pain in fibromyalgia patients. Patients aged ≥18 years who had met the criteria for fibromyalgia were randomized to receive either pregabalin, starting at 150 mg/day and increasing to a maintenance dose of 300 or 450 mg/day, or placebo, for 15 weeks. The primary efficacy endpoint was mean pain score at final assessment. Secondary endpoints included Patient Global Impression of Change (PGIC) together with measures of sleep, physical functioning and quality of life.ResultsA total of 498 patients (89% female) were randomized to receive either pregabalin (n = 250) or placebo (n = 248). Pregabalin significantly reduced mean pain score at final assessment (difference in mean change from baseline, compared with placebo -0.44; P = 0.0046) and at every week during the study (P <0.025). Key secondary endpoints were also significantly improved with pregabalin treatment compared with placebo, including PGIC (percentage reporting symptoms "very much improved" or "much improved", 38.6% vs 26.7% with placebo; P = 0.0078); pain visual analog scale (difference in mean change from baseline, compared with placebo -6.19; P = 0.0013); Fibromyalgia Impact Questionnaire total score (-3.33; P = 0.0144); and quality of sleep score (-0.73; P <0.0001). Treatment was generally well tolerated, with somnolence and dizziness the most frequently reported adverse events.ConclusionsThis trial demonstrated that pregabalin, at doses of up to 450 mg/day, was effective for the symptomatic relief of pain in Japanese patients with fibromyalgia. Pregabalin also improved measures of sleep and functioning and was well tolerated. These data indicate that pregabalin is an effective treatment option for the relief of pain and sleep problems in Japanese patients with fibromyalgia.Trial RegistrationClinicalTrials.gov: NCT00830167
This study was designed to test whether concentration or dose of NaCl was responsible for the initial tissue damage (after 1 min) and resulting temporary cell proliferation at 17 h in stomach mucosa of male F344 rats after gastric intubation of 0.65, 1.3, 2.6 and 3.7 M NaCl. Histological damage was studied by dual staining combining horseradish peroxidase-labeled Griffonia simplicifolia agglutinin-II staining (HRP-GSA-II) and periodic acid cold thionin-Schiff reaction (PATS). Cell proliferation was studied by measuring replicative DNA synthesis with liquid scintillation counting and by BrdU staining. NaCl at the same overall dose of 0.8 g/kg body weight induced different degrees of response depending on the concentration. For 4 ml of 0.65 M NaCl, there was no tissue damage after 1 min nor any increase in replicative DNA synthesis after 17 h in the pyloric mucosa. Administration of 1.3 M NaCl (2 ml), 2.6 M NaCl (1 ml) and 3.7 M NaCl (0.7 ml) induced concentration-dependent damage of the surface mucous cell layer after 1 min and increased replicative DNA synthesis after 17 h (P<0.05). Concentration-dependent increase in replicative DNA synthesis at 17 h was also induced with the same volume (1 ml) of 1.3, 2.6, and 3.7 M NaCl, while a volume-dependent increase in replicative DNA synthesis at 17 h was induced with 0.4, 0.7 and 1 ml of 3.7 M NaCl. However, a greater increase in replicative DNA synthesis was always observed when using higher NaCl concentrations at the same dose. Liquid scintillation counting was well-correlated with BrdU staining. These results suggest that a high concentration of NaCl is responsible for the initial tissue damage and resulting temporary cell proliferation during stomach tumor promotion.
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