Antinociceptive Effects of Ginsenoside Rg3 in a Rat Model of Incisional Pain

Abstract

Background: Ginsenoside Rg3 is an extract of total ginseng saponins, which accounts for 4.7% of all saponins. This study aimed to identify the mechanisms of the antinociceptive effects of ginsenoside Rg3. Methods: Rats were randomly divided into six groups, which were treated with vehicle or 0.5, 1, 1.5, 2, or 4 mg/kg of ginsenoside Rg3 intraperitoneally 2 h after a plantar incision was made. To evaluate the mechanisms of antinociceptive effects, the rats were intraperitoneally injected with naloxone 5 mg/kg, atropine 1 mg/kg, yohimbine 2 mg/kg, mecamylamine 1 mg/kg, prazosin 1 mg/kg, and dexmedetomidine 5 μg/kg. Hyperalgesia produced by the plantar incision was assessed using von Frey filaments 1 day before the incision (BI) and 2 h after the plantar incision (AP); this measurement was repeated at 15, 30, 45, 60, 80, 100 and 120 min, and 24 and 48 h after the injection of ginsenoside Rg3. Serum interleukin-1β (IL-1β) and interleukin-6 (IL-6) levels were measured 1 day before incision and 120 min, 24 h, and 48 h after the injection of ginsenoside Rg3 or vehicle. Results: The mechanical withdrawal threshold (MWT) significantly increased in the group that received ginsenoside Rg3. The dose-MWT response showed a curvilinear, bell-shaped relationship. The maximum MWT was found with the administration of ginsenoside Rg3 at 1.5 mg/kg; MWT decreased to 2 and 4 mg/kg. Yohimbine diminished the analgesic effect of ginsenoside Rg3. Prazosin and dexmedetomidine increased the analgesic effect of ginsenoside Rg3. IL-1β and IL-6 appeared significantly lower relative to control group. Conclusions: Ginsenoside Rg3 has an analgesic effect with a curvilinear dose-response relationship. Alpha 2 adrenergic receptor appeared to be related to the analgesic effect of ginsenoside Rg3. Also, the anti-inflammatory effect of ginsenoside Rg3 could be related to its analgesic effect.