Antinociceptive effect of intrathecal ginsenosides through α-2 adrenoceptors in the formalin test of rats

Abstract

Background. We defined the nature of the pharmacological interaction after intrathecal co-administration of ginsenosides with clonidine, and clarified the contribution of the α-2 adrenoceptors on the effect of ginsenosides. Methods. Pain was evoked by injection of a formalin solution (5, 50 μl) into the hindpaw of male SpragueDawley rats. Isobolographic analysis was performed to characterize the drug interaction between ginsenosides and clonidine. The antagonism of ginsenosides-mediated antinociception was determined with α-2A (BRL 44408), α-2B (ARC 239), and α-2C (JP 1302) adrenoceptor antagonists. The expression of α-2 adrenoceptor subtypes was examined by reverse transcriptasepolymerase chain reaction. Results. Intrathecal ginsenosides (n=29) and clonidine (n=31) displayed an antinociceptive effect. The ED50 values (95 confidence intervals) of ginsenosides and clonidine for phases 1 and 2 were 109.5 (63-190.3) and 110.9 (57.1-215.5), and 11.8 (3.7-37.1) and 4.9 (3.1-6.7) μg, respectively. With an isobolographic study (n=48), the ED50 values (95 confidence intervals) of ginsenosides in the combination of ginsenosides and clonidine for phases 1 and 2 were 58.2 (38.9-87.3) and 57.2 (46.5-70.3) μg, respectively. Intrathecal BRL 44408 (n=6), ARC 239 (n=5), and JP 1302 (n=5) reversed the antinociception of ginsenosides in both phases (P<0.01, <0.001). The injection of formalin increased the expression of α-2C adrenoceptor in the spinal cord (P<0.05). Conclusions. Intrathecal ginsenosides additively interacted with clonidine in the formalin test. Furthermore, α-2A,-B, and-C adrenoceptors contributed to the antinociception of intrathecal ginsenosides. © The Author [2010].