232 Korean J Pain Vol. 23, No. 4, 2010 Fig. 1. Radiographics of sham-injected (A) and NCTC 2472 tumor cells-injected mice. Tumor cells were inoculated into the femur and radiological examination was done at 14 (B) and 21 (C) days after tumor cells injection. Tumor cells injections induced bone tumor and osteolysis over time. No change was seen in sham group. Arrows head indicated the bone destruction. 5 × 5 cm) and allowed to adapt for 20-30 min before the experiments. Intrathecal ginsenosides (150, 500, 1,000 μg, n = 19) were administered and the withdrawal threshold was measured at 15, 30, 60, 90, and 120 min after delivery of ginsenosides. Intrathecal DMSO was used as a control (n = 3). The withdrawal threshold measured before tumor cells injection was regarded as the baseline threshold. Each mouse was tested only once. The investigator was blind to the experimental conditions in all cases. To examine the abnormal behaviors of ginsenosides, additional naive rats (n = 5) were given intrathecal ginse- nosides (1,000 μg), and examined at 15, 30, 60, 90, and 120 min after administration. The righting and plac- ing-stepping reflexes were checked for evaluation of motor function. The first was tested by placing the mice prone on the table, which normal mice immediately take a pos- ture to an upright position. The latter was tested by plac- ing the dorsum of hind paw across the edge of the table, which normal mice put their paws forward into a position for walking. Next, pinna and corneal reflexes were eval- uated with a paper string [19]. The first was tested by stimulation of the ear canal, which normal mice sponta- neously shake their heads. The latter was tested by stim- ulation of the cornea, which normal mice spontaneously blink. All of four reflexes were judged as present or absent. The data are expressed as mean ± SEM. The time- response data are presented as the withdrawal threshold in g. The dose-response data are presented as percentage of maximal possible effect (%MPE) according to the formula. %MPE = Postdrug threshold - baseline threshold Cut-off threshold (3.6) - baseline threshold × 100% The dose-response data were analyzed using one-way analysis of variance (ANOVA). Differences in the with- drawal threshold between the sham and tumor mice were Fig. 2. Time course of the withdrawal response to von Frey filaments after tumor cells injection. Each line represents mean ± SEM of 4−6 mice. B = baseline withdrawal threshold measured before tumor cells injection. Paw withdrawal threshold (g) was plotted versus time in days. A significant difference was noted between the tumor and sham groups. *P ＜ 0.05. analyzed using unpaired t-tests. Results were statistically significant in case of P ＜ 0.05. RESULTS NCTC 2472 tumor cells inoculation into the intra- medullary cavity of distal femur of mice radiographically induced bone destruction over time (Fig. 1). However, the bone tumor was not noted in MEM-injected femur (sham) until 21 days after injection. The inoculation of tumor cells into the femur resulted in a decrease of the withdrawal threshold in injected site (Fig. 2). By contrast, no change of the withdrawal threshold was noted in mice with sham injection. Intrathecal administration of ginsenosides dose-de- pendently increased the withdrawal threshold in mice with