234 Korean J Pain Vol. 23, No. 4, 2010 histamine [21], which suggests that these chemicals may be involved in the action mechanism of ginsenosides. Furthermore, recently it has been reported that opioid re- ceptors may play an important role in the antinociceptive mechanism of action of ginsenosides at the spinal level [14]. Previous studies have also shown that the nicotinic acetylcholine receptor may contribute to the mechanism of action of ginsenosides [15,22]. Moreover, several lines of evidence suggest that Ca2＋ channels play an important role in the pharmacological activity of ginsenosides [23-25]. On the other hand, it has been reported that alpha2, mus- carinic, and GABA receptors are not the pharmacological sites of action of ginsenosides [23,26]. There were some limitations in this study. First, the authors only evaluated the effect of ginsenosides. More researches with different types of chemicals may be need- ed for the determination of the mechanism of action of ginsenosides. Second, the authors just used the behavioral study. Molecular works may help to examine the action mechanism of ginsenosides. Spinal ginsenosides are not yet available clinically. However, ginsenosides may be used effectively in the management of bone cancer pain in the future. Thus, this is the first report which proposed the possibility for clinical use of ginsenosides. Taken together, injection of NCTC 2472 tumor cells into the femur of mice caused bone tumor and pain. Intrathecal ginsenosides dose-dependently attenuated the bone cancer pain. Therefore, spinal ginsenosides may be useful for managing bone cancer pain. ACKNOWLEDGEMENTS This work was supported by National Research Foun- dation of Korea Grant funded by the Korean Goverment (KRF-2007-521-E00096). REFERENCES 1. Portenoy RK, Lesage P. Management of cancer pain. Lancet 1999; 353: 1695-700. 2. Banning A, Sjøgren P, Henriksen H. Pain causes in 200 patients referred to a multidisciplinary cancer pain clinic. Pain 1991; 45: 45-8. 3. Coleman RE, Houston S, Purohit OP, Rubens RD, Kandra A, Ford J. A randomised phase II study of oral pamidronate for the treatment of bone metastases from breast cancer. Eur J Cancer 1998; 34: 820-4. 4. Coleman RE. How can we improve the treatment of bone metastases further? Curr Opin Oncol 1998; 10(Suppl 1): S7-13. 5. Mercadante S, Arcuri E. Breakthrough pain in cancer patients: pathophysiology and treatment. Cancer Treat Rev 1998; 24: 425-32. 6. Mercadante S. Malignant bone pain: pathophysiology and treatment. Pain 1997; 69: 1-18. 7. Portenoy RK, Payne D, Jacobsen P. Breakthrough pain: characteristics and impact in patients with cancer pain. Pain 1999; 81: 129-34. 8. Mercadante S, Fulfaro F. Management of painful bone metastases. Curr Opin Oncol 2007; 19: 308-14. 9. O'Connor JP, Lysz T. Celecoxib, NSAIDs and the skeleton. Drugs Today (Barc) 2008; 44: 693-709. 10. Vanderah TW, Gardell LR, Burgess SE, Ibrahim M, Dogrul A, Zhong CM, et al. Dynorphin promotes abnormal pain and spinal opioid antinociceptive tolerance. J Neurosci 2000; 20: 7074-9. 11. Liu CX, Xiao PG. Recent advances on ginseng research in China. J Ethnopharmacol 1992; 36: 27-38. 12. Attele AS, Wu JA, Yuan CS. Ginseng pharmacology: multiple constituents and multiple actions. Biochem Pharmacol 1999; 58: 1685-93. 13. Nah JJ, Hahn JH, Chung S, Choi S, Kim YI, Nah SY. Effect of ginsenosides, active components of ginseng, on capsaicin- induced pain-related behavior. Neuropharmacology 2000; 39: 2180-4. 14. Shin DJ, Yoon MH, Lee HG, Kim WM, Park BY, Kim YO, et al. The effect of treatment with intrathecal ginsenosides in a rat model of postoperative pain. Korean J Pain 2007; 20: 100-5. 15. Kim SY, Yoon MH, Lee HG, Kim WM, Lee JD, Kim YO, et al. The role of adrenergic and cholinergic receptors on the antinociception of Korean red ginseng in the spinal cord of rats. Korean J Pain 2008; 21: 27-32. 16. Schwei MJ, Honore P, Rogers SD, Salak-Johnson JL, Finke MP, Ramnaraine ML, et al. Neurochemical and cellular reorganization of the spinal cord in a murine model of bone cancer pain. J Neurosci 1999; 19: 10886-97. 17. Hylden JL, Wilcox GL. Intrathecal morphine in mice: a new technique. Eur J Pharmacol 1980; 67: 313-6. 18. Dixon WJ. Efficient analysis of experimental observations. Annu Rev Pharmacol Toxicol 1980; 20: 441-62. 19. Yoon MH, Choi JI, Jeong SW. Antinociception of intrathecal cholinesterase inhibitors and cholinergic receptors in rats. Acta Anaesthesiol Scand 2003; 47: 1079-84. 20. Nah SY. Ginseng; recent advances and trends. Korean J Ginseng Sci 1997; 21: 1-12. 21. Kaku T, Miyata T, Uruno T, Sako I, Kinoshita A. Chemico-