Centre for Pain Medicine and Palliative Care, Monash Institute of Medical Research, Monash University, Clayton, Victoria, Australia.
Pain Med. 2010 Jan;11(1):106-18. doi: 10.1111/j.1526-4637.2009.00768.x.
This study determined the antihyperalgesic effect of CNSB002, a sodium channel blocker with antioxidant properties given alone and in combinations with morphine in rat models of inflammatory and neuropathic pain.
Dose response curves for nonsedating doses of morphine and CNSB002 given intraperitoneally alone and together in combinations were constructed for antihyperalgesic effect using paw withdrawal from noxious heat in two rat pain models: carrageenan-induced paw inflammation and streptozotocin (STZ)-induced diabetic neuropathy.
The maximum nonsedating doses were: morphine, 3.2 mg/kg; CNSB002 10.0 mg/kg; 5.0 mg/kg CNSB002 with morphine 3.2 mg/kg in combination. The doses calculated to cause 50% reversal of hyperalgesia (ED50) were 7.54 (1.81) and 4.83 (1.54) in the carrageenan model and 44.18 (1.37) and 9.14 (1.24) in the STZ-induced neuropathy model for CNSB002 and morphine, respectively (mg/kg; mean, SEM). These values were greater than the maximum nonsedating doses. The ED50 values for morphine when given in combination with CNSB002 (5 mg/kg) were less than the maximum nonsedating dose: 0.56 (1.55) in the carrageenan model and 1.37 (1.23) in the neuropathy model (mg/kg; mean, SEM). The antinociception after morphine (3.2 mg/kg) was increased by co-administration with CNSB002 from 28.0 and 31.7% to 114.6 and 56.9% reversal of hyperalgesia in the inflammatory and neuropathic models, respectively (P < 0.01; one-way analysis of variance-significantly greater than either drug given alone).
The maximum antihyperalgesic effect achievable with nonsedating doses of morphine may be increased significantly when the drug is used in combination with CNSB002.
本研究旨在确定 CNSB002 的抗痛觉过敏作用，CNSB002 是一种具有抗氧化特性的钠离子通道阻滞剂，单独使用以及与吗啡联合使用时，可在炎症和神经病理性疼痛的大鼠模型中发挥作用。
构建腹腔内给予非镇静剂量吗啡和 CNSB002 单独使用以及联合使用的剂量反应曲线，以评估对两种大鼠疼痛模型（角叉菜胶诱导的足爪炎症和链脲佐菌素（STZ）诱导的糖尿病性神经病变）中有害热刺激引起的痛觉过敏的抗痛觉过敏作用。
最大非镇静剂量为：吗啡，3.2mg/kg；CNSB002，10.0mg/kg；5.0mg/kg CNSB002 与吗啡 3.2mg/kg 联合使用。在角叉菜胶模型中，引起痛觉过敏 50%逆转的剂量（ED50）分别为 7.54（1.81）和 4.83（1.54），在 STZ 诱导的神经病变模型中，CNSB002 和吗啡分别为 44.18（1.37）和 9.14（1.24）（mg/kg；均值，SEM）。这些值大于最大非镇静剂量。当与 CNSB002（5mg/kg）联合使用时，吗啡的 ED50 值小于最大非镇静剂量：在角叉菜胶模型中为 0.56（1.55），在神经病变模型中为 1.37（1.23）（mg/kg；均值，SEM）。在炎症和神经病变模型中，吗啡（3.2mg/kg）与 CNSB002 联合使用后，镇痛作用增加，痛觉过敏逆转率分别从 28.0%和 31.7%增加到 114.6%和 56.9%（P<0.01；单向方差分析-显著大于单独使用任一药物）。
当与 CNSB002 联合使用时，非镇静剂量吗啡可实现的最大抗痛觉过敏作用可能会显著增加。
