Analgesic effects of minodronate in a rat chronic pain model

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.