MH Yoon, et al / Intrathecal and Bone Cancer Pain 233 Fig. 3. Effects of intrathecal ginsenosides on the withdrawal response to von Frey filaments after tumor cells injection. The data are presented as the withdrawal threshold (A) or percent of the maximum possible effect (%MPE, B). Each line or bar represents mean ± SEM of 5−6 mice. B = baseline withdrawal threshold measured before tumor cells injection. DMSO = dimethylsulfoxide. The withdrawal threshold was measured immediately before ginsenosides delivery, and intrathecal ginsenosides were administered at time 0 (arrow). The withdrawal threshold was dose-dependently increased with ginsenosides. *P < 0.05, †P ＜ 0.01. tumor cells inoculation (Fig. 3). At 150 μg, intrathecal gin- senosides did not affect the withdrawal threshold. At 500 μg, ginsenosides increased the withdrawal threshold, how- ever, the effect was progressively declined. At 1,000 μg, the effect was maintained during the entire observation period. After the intrathecal delivery of ginsenosides, the righting, placing-stepping, the pinna and corneal reflexes were present. DISCUSSION In the present study, we evaluated the analgesic effect of ginsenosides in bone cancer pain model. The injection of NCTC 2472 tumor cells into the femur resulted in an osteolysis and decreased the withdrawal threshold in tumor cells-injected site. These observations indicated that the intrafemoral injection of NCTC 2472 tumor cells may prop- erly induce bone tumor and bone cancer pain model as re- ported previously [16]. To date, NSAIDs and opiates have been considered as typical analgesics for bone cancer pain [8]. However, de- spite a variety of pharmacotherapies for bone cancer pain, the effect is relatively poor. Such difficulty of treatment is caused by a lack of knowledge of the basic neurobiology of bone cancer pain. But, the use of the mouse bone can- cer model used in this study may expedite the under- standing of the pathophysiology of bone cancer pain and advance the development of novel analgesics for treating bone cancer pain. In this study, intrathecal ginsenosides produced a dose-dependent increase of the withdrawal threshold in the bone cancer site. Furthermore, the antinociceptive ef- fect was persistent during the observation period at the highest dose. These findings suggest that ginsenosides are active against bone tumor pain at the spinal level. Ginseng has long been used in Eastern Medicine medicine to im- prove the weakened physical status brought on by stress or disease [11]. Ginsenosides, ginseng saponins, are the major components responsible for the effects of ginseng [20]. Previous experiments also suggest that ginsenosides are effective to a variety of nociceptive conditions. Intra- thecal ginsenosides inhibit formalin-induced, substance P-induced and paw incision-induced pain behaviors in an- imals [13-15]. These observations, thus suggest that gin- seng may afford an antinociceptive action in the spinal cord. In spite of the wide use of ginsenosides in a various medical fields, the mechanism of action remains to be determined. Chemically, ginsenosides have a four-ring, steroid-like structure with sugar moieties attached and show properties similar to acetylcholine, adrenaline, and