Analgesic effects of minodronate on formalin-induced acute inflammatory pain in rats

Minodronate is expected to produce greater analgesic effects than other bisphosphonates. However, there are no studies comparing bisphosphonate analgesic effects on formalin-induced acute inflammatory pain in rats. The purpose of the present study was to evaluate the analgesic effects of minodronate, morphine, and placebo. Four-month-old female Wistar rats were administered minodronate (50 mg/kg), morphine (10 mg/kg), or vehicle (n = 10 each) injections. Thirty minutes later, all rats were injected with formalin (right hind paw) to induce acute inflammatory pain. Paw licking and lifting as indicators of nociceptive pain responses were monitored from 0 to 5 min (phase 1; chemical-stimulation state) and then from 10 to 30 min (phase 2; spinal-sensitized state) after injection. The percentage of limb usage of the formalin-injected and the non-injected sides were measured in phases 1 and 2 by counting foot stamps. Minodronate significantly decreased nociceptive responses and increased limb usage compared with vehicle in phase 2 only (P < 0.05). Morphine significantly decreased nociceptive responses and increased limb usage compared with minodronate and vehicle in both phase 1 and 2 (P < 0.05). In conclusion, minodronate showed significant analgesic effects for formalin-induced acute pain in the spinal-sensitized state.