We evaluated the analgesic effects of minodronate, alendronate and pregabalin on mechanical and thermal allodynia, as well as changes in bone mineral density and skeletal muscle volume caused by chronic constriction injury (CCI) in an ovariectomized rat. Ovariectomy was performed on four-week-old female Wistar rats. Thereafter, at 8-weeks of age, the left sciatic nerve was ligated to create the chronic pain model (CCI limb), and sham surgery was performed on the right hindlimb. In all rats, either minodronate (0.15 mg/kg/week), alendronate (0.15 mg/kg/week), pregabalin (10 mg/kg/week), or their vehicle was administered for 2 weeks starting on the 0th day of CCI. Behavioral evaluations, with von Frey testing and the hot plate test, were performed on days 0, 7 and 14. After 2 weeks, bilateral femurs and tibialis anterior muscles were harvested for bone mineral density and cross sectional area measurements, respectively. Two weeks treatment with minodronate significantly improved mechanical and thermal allodynia evaluated by the von Frey and hot plate tests in the CCI limb (P < 0.05). Minodronate and alendronate treatment for 2 weeks significantly increased total femoral bone mineral density in the CCI limb compared with pregabalin or vehicle treatment (P < 0.01). Cross sectional area of the CCI limb in the minodronate group was significantly larger than that of the alendronate group (P < 0.05) and pregabalin group (P < 0.05). Two-week treatment with minodronate, but not alendronate or pregabalin, improved mechanical and thermal allodynia caused by CCI in ovariectomized rats.

中文翻译：

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米诺膦酸盐在大鼠慢性疼痛模型中的镇痛作用。

我们评估了去甲卵巢大鼠对机械性和热性异常性疼痛的米诺膦酸盐，阿仑膦酸盐和普瑞巴林的镇痛作用，以及由于慢性收缩损伤（CCI）引起的骨矿物质密度和骨骼肌体积的变化。对四周大的雌性Wistar大鼠进行卵巢切除术。此后，在8周龄时，结扎左坐骨神经以创建慢性疼痛模型（CCI肢体），并在右后肢进行假手术。在所有大鼠中，从CCI的第0天开始，连续2周施用米诺膦酸盐（0.15 mg / kg /周），阿仑膦酸盐（0.15 mg / kg /周），普瑞巴林（10 mg / kg /周）或它们的媒介物。在第0、7和14天通过von Frey测试和热板测试进行行为评估。分别收获双侧股骨和胫骨前肌用于骨矿物质密度和横截面积的测量。通过von Frey和热板试验评估的CCI肢体，米诺膦酸盐治疗两周显着改善了机械和热异常性疼痛（P <0.05）。与普瑞巴林或赋形剂治疗相比，米诺膦酸和阿仑膦酸盐治疗2周可显着增加CCI肢体的总股骨矿物质密度（P <0.01）。米诺膦酸盐组CCI肢体的横截面积显着大于阿仑膦酸盐组（P <0.05）和普瑞巴林组（P <0.05）。用米诺膦酸盐治疗两周，但不使用阿仑膦酸盐或普瑞巴林，可改善卵巢切除大鼠CCI引起的机械性和热性异常性疼痛。