Neurobiology 2, Centre de Recherche Pierre-Fabre, 17 avenue Jean Moulin, 81106 Castres, France.
Eur J Pharmacol. 2011 Dec 15;672(1-3):83-7. doi: 10.1016/j.ejphar.2011.09.182. Epub 2011 Oct 6.
The role of antidepressants in the treatment of visceral pain has not been extensively examined. Milnacipran, a serotonin/noradrenalin reuptake inhibitor, has recently been approved in the USA for fibromyalgia, a chronic pathology characterized by diffused/chronic musculoskeletal pain, and a high prevalence of irritable bowel syndrome. Here, we determined its antinociceptive efficacy in two visceral pain tests in rodents: the acetic acid-induced writhing model in mice and the butyrate/colonic distension assay in rats, a model of irritable bowel syndrome. Acute milnacipran (5-40 mg/kgi.p.) significantly and dose-dependently reduced writhing (72.2 ± 3.2 versus 17.0 ± 4.1 writhes at 40 mg/kg). Following repeated administration (40 m/kgi.p. for 5 days), milnacipran preserved its ability to significantly reduce writhing (76 ± 8.3 versus 21.1 ± 6.7 writhes). Similarly, in the butyrate model, acute milnacipran (17.5 and 35 mg/kg, i.p.) significantly and dose-dependently increased cramps induction thresholds (from 45.7 ± 5.7 to 66.3 ± 4.8 and 75.6 ± 2.9 mm Hg, for 17.5 and 35 mg/kg, respectively) and reduced the number of cramps (from 3.0 ± 0.8 to 1.2 ± 0.8 and 0.3 ± 0.3 following inflation of an intra-rectal balloon. To summarise, milnacipran was efficacious in the writhing test, after acute and semi-chronic administration. This effect was confirmed after acute administration in a more specific model of colonic hypersensitivity induced by butyrate. This suggests that milnacipran has potential clinical application in the treatment of visceral pain, such as in irritable bowel syndrome, highly co-morbid with fibromyalgia.
抗抑郁药在治疗内脏疼痛中的作用尚未得到广泛研究。米那普仑是一种 5-羟色胺/去甲肾上腺素再摄取抑制剂，最近已在美国获准用于纤维肌痛的治疗。纤维肌痛是一种慢性疾病，其特征为弥漫性/慢性肌肉骨骼疼痛和较高的肠易激综合征发病率。在这里，我们在两种啮齿动物内脏疼痛模型中确定了米那普仑的抗伤害感受作用：在小鼠中醋酸诱导的扭体模型和大鼠丁酸/结肠扩张模型（肠易激综合征模型）。米那普仑（5-40 mg/kg，i.p.）急性给药显著且呈剂量依赖性地减少扭体反应（40 mg/kg 时为 72.2 ± 3.2 次与 17.0 ± 4.1 次）。在重复给药（40 m/kg，连续 5 天）后，米那普仑仍能显著减少扭体反应（76 ± 8.3 次与 21.1 ± 6.7 次）。同样，在丁酸模型中，米那普仑（17.5 和 35 mg/kg，i.p.）急性给药也显著且呈剂量依赖性地增加痉挛诱导阈值（分别从 45.7 ± 5.7 增加至 66.3 ± 4.8 和 75.6 ± 2.9 mm Hg，17.5 和 35 mg/kg），并减少痉挛次数（从 3.0 ± 0.8 减少至 1.2 ± 0.8 和 0.3 ± 0.3，在直肠内气囊充气后）。总之，米那普仑在急性和半慢性给药后在扭体试验中有效。在更特异的由丁酸诱导的结肠高敏性模型中急性给药也证实了这一作用。这表明米那普仑可能在治疗内脏疼痛方面具有潜在的临床应用，例如在纤维肌痛高度共病的肠易激综合征中。
