Abstract：
We aimed to examine the efficacy of combination therapies of Neurotropin® with tramadol and Neurotropin with mirogabalin for neuropathic pain management. A neuropathic pain model (L5 spinal nerve ligation model: L5-SNL) using male Wistar rats was generated through tight ligation of the left fifth lumbar nerve using silk sutures. Mechanical allodynia was assessed using the 50% paw withdrawal threshold. The combined antiallodynic effects were evaluated using isobolographic analyses. Small intestinal transit was evaluated using the charcoal meal test, and motor coordination using the rota-rod test. Neurotropin (50-200 NU/kg, p.o.), tramadol (7.5-60 mg/kg, p.o.), and mirogabalin (3-30 mg/kg, p.o.) showed a dose-dependent antiallodynic effect in L5-SNL rats. The combined antiallodynic effects of Neurotropin and tramadol were additive or synergistic, whereas those of Neurotropin and mirogabalin were additive. Neurotropin (100-400 NU/kg, p.o.) did not affect the small intestinal transit, whereas tramadol (30-100 mg/kg, p.o.) significantly inhibited it. Neurotropin (100-400 NU/kg, p.o.) did not affect the walking time, whereas mirogabalin (10-100 mg/kg, p.o.) significantly decreased it. Neurotropin dose-dependently ameliorated mechanical allodynia in rats, and combination therapy with Neurotropin-tramadol or Neurotropin-mirogabalin may alleviate neuropathic pain without aggravating the adverse effects of tramadol and mirogabalin.
摘要：
我们旨在研究Neurotropin®与曲马多和Neurotropin与米罗加巴林联合治疗神经性疼痛的疗效。使用雄性Wistar大鼠通过使用丝线缝线紧密结扎左第五腰神经来产生神经性疼痛模型(L5脊神经结扎模型:L5-SNL)。使用50%缩爪阈值评估机械异常性疼痛。使用等值线分析评估了联合的抗痛觉异常作用。使用木炭粉测试评估小肠运输，和电机协调使用旋转杆测试。Neurotropin(50-200NU/kg,p.o.),曲马多（7.5-60毫克/千克，p.o.),和米罗加巴林(3-30毫克/千克，p.o.）在L5-SNL大鼠中显示出剂量依赖性的抗痛觉异常作用。神经妥乐平和曲马多的联合抗痛觉过敏作用是累加或协同作用，而神经妥乐平和米罗加巴林是加性的。Neurotropin(100-400NU/kg,p.o.)不影响小肠运输，而曲马多(30-100毫克/千克，p.o.）显着抑制了它。Neurotropin(100-400NU/kg,p.o.)没有影响步行时间，而米罗加巴林(10-100毫克/千克，p.o.）显着降低了它。神经妥乐平剂量依赖性改善大鼠机械性异常疼痛，与神经妥乐平-曲马多或神经妥乐平-米罗加巴林联合治疗可减轻神经性疼痛而不加重曲马多和米罗加巴林的不良反应。
