title: Antinociceptive effect of intrathecal ginsenosides through alpha-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 Sprague-Dawley 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 transcriptase-polymerase chain reaction.
  
  
  RESULTS
  Intrathecal ginsenosides (n=29) and clonidine (n=31) displayed an antinociceptive effect. The ED(50) 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 ED(50) 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.
authors.affiliation: Department of Anesthesiology and Pain Medicine, Chonnam National University, Medical School, Republic of Korea. mhyoon@chonnam.ac.kr
authors.forename: M H
authors.initials: MH
authors.lastname: Yoon
authors.forename: L J
authors.initials: LJ
authors.lastname: Huang
authors.forename: J I
authors.initials: JI
authors.lastname: Choi
authors.forename: H G
authors.initials: HG
authors.lastname: Lee
authors.forename: W M
authors.initials: WM
authors.lastname: Kim
authors.forename: C M
authors.initials: CM
authors.lastname: Kim
mesh_terms: D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003000:Clonidine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004347:Drug Interactions; D005786:Gene Expression Regulation / Q000187:drug effects; D036145:Ginsenosides / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D007278:Injections, Spinal; D008297:Male; D010146:Pain / Q000139:chemically induced / Q000517:prevention & control*; D010147:Pain Measurement / Q000379:methods; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000096:biosynthesis / Q000187:drug effects* / Q000235:genetics
chemical_list: D018712:Analgesics, Non-Narcotic; D036145:Ginsenosides; D012333:RNA, Messenger; D018341:Receptors, Adrenergic, alpha-2; D003000:Clonidine