Antinociceptive effects of Ginsenoside Rb1 in a rat model of cancer-induced bone pain

Ginsenoside Rb1 (GRb1) is a major ingredient of ginseng, a traditional medicine that has been used for thousands of years. Previous studies have reported that GRb1 had anti-inflammatory, antioxidant and neuroprotective effects. The current study aimed to evaluate the antinociceptive effects of GRb1 in a rat model of cancer-induced bone pain (CIBP) established by intratibial injection of Walker 256 cells. Intraperitoneal injection (i.p.) of GRb1 (5 and 10 mg/kg, but not 1 mg/kg) partially and transiently reversed the mechanical allodynia and thermal hyperalgesia in CIBP rats at 14 days following surgery when the pain behavior is established. Furthermore, repeated administration of GRb1 demonstrated persistent analgesic effect. Additionally, the protein expression and immunoreactivity of iba1, which is the maker of microglia, was significantly suppressed in CIBP rats treated with GRb1 (i.p., 10 mg/kg) from day 12 for three consecutive days compared with CIBP rats treated with a vehicle. Furthermore, upregulation of spinal interleukin (IL)-1β, IL-6 and tumor necrosis factor-α were also significantly inhibited by the treatment of GRb1 (i.p., 10 mg/kg) from day 12 for three consecutive days. Together, these results indicated that GRb1 may attenuate CIBP via inhibiting the activation of microglia and glial-derived proinflammatory cytokines.