Onal Aytül, Parlar Ayşe, Ulker Sibel
Department of Pharmacology and Clinical Pharmacology, Faculty of Medicine, Ege University, 35100 Bornova, Izmir, Turkey.
Pharmacol Biochem Behav. 2007 Dec;88(2):171-8. doi: 10.1016/j.pbb.2007.08.001. Epub 2007 Aug 15.
Milnacipran is a non-tricyclic antidepressant drug which selectively inhibits serotonin and noradrenaline re-uptake and is recommended in the treatment of various chronic pain syndromes. Many studies have shown that compounds known to block monoamine uptake potentiate the antinociceptive effects of opioids. This study investigates the effect of milnacipran alone or in combination with an opiodergic drug, i.e. tramadol, on hyperalgesia in a rat model of neuropathic pain. The contribution of serotonergic, noradrenergic and opioidergic systems in the potential antihyperalgesic effect of milnacipran has also been examined. Chronic constriction injury was induced in rats by loose ligation of the sciatic nerve and neuropathic pain was evaluated 14 days after surgery. Intraperitoneal acute injection of milnacipran 60 mg/kg produced an antihyperalgesic effect which was prevented by pretreating systemically with alpha-methyl-p-tyrosine, an inhibitor of noradrenaline synthesis; parachlorophenylalanine, an inhibitor of serotonin synthesis; and naloxone, an antagonist of opioidergic receptors. Co-administration of milnacipran 40 mg/kg with tramadol (20 and 40 mg/kg) potentiated the antihyperalgesic effect of tramadol. Milnacipran has an antihyperalgesic effect mediated by serotonergic, noradrenergic and opioidergic systems and the combined use of tramadol with milnacipran potentiates the effect of tramadol in the management of neuropathic pain.
米那普明是一种非三环类抗抑郁药，它能选择性抑制5-羟色胺和去甲肾上腺素的再摄取，被推荐用于治疗各种慢性疼痛综合征。许多研究表明，已知能阻断单胺摄取的化合物可增强阿片类药物的镇痛作用。本研究调查了米那普明单独使用或与一种阿片类药物（即曲马多）联合使用对神经性疼痛大鼠模型痛觉过敏的影响。还研究了5-羟色胺能、去甲肾上腺素能和阿片类系统在米那普明潜在抗痛觉过敏作用中的贡献。通过对大鼠坐骨神经进行宽松结扎诱导慢性压迫性损伤，并在手术后14天评估神经性疼痛。腹腔内急性注射60mg/kg米那普明产生了抗痛觉过敏作用，而预先全身给予去甲肾上腺素合成抑制剂α-甲基-对-酪氨酸、5-羟色胺合成抑制剂对氯苯丙氨酸和阿片类受体拮抗剂纳洛酮可阻止这种作用。40mg/kg米那普明与曲马多（20mg/kg和40mg/kg）联合给药可增强曲马多的抗痛觉过敏作用。米那普明具有由5-羟色胺能、去甲肾上腺素能和阿片类系统介导的抗痛觉过敏作用，曲马多与米那普明联合使用可增强曲马多在治疗神经性疼痛中的效果。
