Antinociceptive Effects of Ginsenosides Injected Intracerebroventricularly or Intrathecally in Substance P-Induced Pain Model

Abstract

We have examined the effects of several ginsenosides (R_b1, R_b2, R_c, R_d, R_e, R_f, R_g1 and R_g3) adminstered intracerebroventricularly (i. c. v.) or intrathecally (i. t.) on the nociceptive behavior induced by substance P (0.7 μg) injected i. t. Among the several ginsenosides studied, R_b2, R_c, R_d, and R_e, but not R_b1, R_f, R_g1 and R_g3, treated i. c. v. (50 μg) attenuated the nociceptive behavior induced by substance P injected i. t. On the other hand, we found that i. t. treatment with 50 μg of R_b1, R_b2, R_d, or R_f effectively attenuated the nociceptive behavior induced by i. t. injected substance P. However, the i. t. treatment with the same doses of R_c, R_e, R_g1 or R_g3 was not effective for antagonizing i. t. injected substance P-induced nociceptive behavior. Our results show that ginsenosides R_b2, R_c, R_d, or R_e injected supraspinally exert a antinociceptive effect in the substance P-induced pain model. Furthermore, R_b1, R_b2, R_d, or R_f treated spinally produce antinociception in the substance P-induced pain model.

Abbreviations

i.c.v.:intracerebroventricular

i.t.:intrathecal

S.E.M.:Standard error of the means

Key Words

Ginsenosides - Panax ginseng C.A. Meyer - Araliaceae - antinociception - supraspinal - spinally - substance P pain model - mouse

References

• 1 Kim H S, Oh K W, Rheu H M, Kim S R. Antagonism of U-50,488H-induced antinociception by ginseng total saponins is dependent on serotonergic mechanisms.  Pharmacol Biochem Behav. 1992;  42 587-93
• 2 Suh H W, Song D K, Huh S O, Kim Y R. Modulatory role of ginsenosides injected intrathecally or intracerebroventricularly in the production of antinociception induced by kappa-opioid receptor agonist administered intracerebroventricularly in the mouse.  Planta Med. 2000;  66 412-7
• 3 Suh H W, Song D K, Kim Y R. Effects of ginsenosides injected intrathecally or intracerebroventricularly on antinociception induced by morphine administrated intracerebroventricularly in the mouse.  Gen Pharmacol. 1997;  29 873-7
• 4 Shin Y R, Jung O M, Nah J J, Nam K Y, Kim C Y, Nah S Y. Ginsenosides that produce differential antinociception in mice.  Gen Pharmacol. 1999;  32 53-9
• 5 Hylden J LK, Wilcox G L. Intrathecal substance P elicits a caudally-directed biting and scratching behavior in mice.  Brain Res. 1981;  217 212-5
• 6 Hunskaar S, Rasmer O B, Hole K. Acetylsalicylic acid, paracetamol and morphine inhibit behavioral responses to intrathecally administered substance P or capsaicin.  Life Sci. 1998;  37 835-41
• 7 Haley T J, McCormick W G. Pharmacological effects produced by intracerebral injections of drugs in the conscious mouse.  Br J Pharmacol. 1957;  12 12-5
• 8 Hylden J LK, Wilcox G L. Intrathecal morphine in mice: a new technique.  Eur J Pharmacol. 1980;  67 313-6
• 9 Dunham N W, Miya T S. A note on a simple apparatus for detecting neurological deficit in rats and mice.  J Am Pharm Assoc. 1957;  46 208-9
• 10 Nah J J, Hahn J H, Chung S, Choi S, Kim Y I, Nah S Y. Effect of ginsenosides, active components of ginseng, on capsaicin-induced pain-related behavior.  Neuropharmacology. 2000;  39 2180-4
• 11 Yoon S R, Nah J J, Shin Y R, Kim S K, Nam K Y, Choi H S, Nah S Y. Ginsenosides induce differential antinociception and inhibit substance P induced-nociceptive response in mice.  Life Sci. 1998;  62 PL319-25
• 12 Mogil J S, Shin Y R, McCleskey E W, Kim S C, Nah S Y. Ginsenoside Rf, a trace component of ginseng root, produces antinociception in mice.  Brain Res. 1998;  792 218-28
• 13 Nemmani K V, Ramarao P. Role of benzodiazepine-GABAA receptor complex in attenuation of U-50,488H-induced analgesia and inhibition of tolerance to its analgesia by ginseng total saponin in mice.  Life Sci. 2002;  70 1727-40