['Current treatments for cancer pain are often inadequate, particularly when metastasis to bone is involved. The addition to the treatment regimen of another drug that has a complementary analgesic effect may increase the overall analgesia without the necessity to increase doses, thus avoiding dose-related side effects. This project investigated the synergistic effect of the addition of the potassium channel (KCNQ2-3) modulator flupirtine to morphine treatment in a rat model of prostate cancer-induced bone pain.', 'Syngeneic prostate cancer cells were injected into the right tibia of male Wistar rats under anesthesia. This led to expanding tumor within the bone in 2 weeks, together with the concurrent development of hyperalgesia to noxious heat. Paw withdrawal thresholds from noxious heat were measured before and after the maximum non-sedating doses of morphine and flupirtine given alone and in combinations. Dose-response curves for morphine (0.13-5.0\u2009mg/kg ip) and flupirtine (1.25-10.0\u2009mg/kg ip) given alone and in fixed-dose combinations were plotted and subjected to an isobolographic analysis.', 'Both morphine (ED₅₀ =\u20090.74\u2009mg/kg) and flupirtine (ED₅₀\u2009=\u20093.32\u2009mg/kg) caused dose-related anti-hyperalgesia at doses that did not cause sedation. Isobolographic analysis revealed that there was a synergistic interaction between flupirtine and morphine. Addition of flupirtine to morphine treatment improved morphine anti-hyperalgesia, and resulted in the reversal of cancer-induced heat hyperalgesia.'] Does flupirtine enhance the anti-hyperalgesic effects of morphine in a rat model of prostate bone metastasis?