Inhibitory effect of processed Aconiti tuber on the development of antinociceptive tolerance to morphine: Evaluation with a thermal assay

In the previous studies, we demonstrated that an oriental herbal medicine processed Aconiti tuber (PAT) at subanalgesic doses could inhibit the development of mechanical antinociceptive tolerance to morphine using the tail pressure test. In the present study, we evaluated whether PAT could inhibit thermal antinociceptive tolerance to morphine using the high temperature (55 °C) hot plate test. Mice received subcutaneous morphine (10 mg/kg), and oral PAT at doses that did not inhibit the hot plate response (0.3, 0.5, 1.0, and 2.0 g/kg), once daily for 14 days. The thermal nociceptive latency was measured at 30 min after daily morphine injections. Compared with placebo, oral PAT partially and dose-dependently inhibited the development of morphine tolerance in morphine-naïve mice, and reversed already-developed morphine tolerance in morphine-tolerant mice. These data suggested that PAT at subanalgesic doses could dose-dependently inhibit and reverse thermal antinociceptive tolerance to morphine.