title: Synergistic interaction between intrathecal ginsenosides and morphine on formalin-induced nociception in rats.
abstract: We defined the nature of the pharmacological interaction between ginsenosides and morphine in a nociceptive state and clarified the role of the different types of opioid receptor in the effects of ginsenosides. An intrathecal catheter was placed in male Sprague-Dawley rats. Pain was induced by formalin injection into the hindpaw. Isobolographic analysis was used to evaluate drug interactions. Furthermore, a nonselective opioid receptor antagonist (naloxone), a μ opioid receptor antagonist (CTOP), a δ opioid receptor antagonist (naltrindole), and a κ opioid receptor antagonist (GNTI) were given intrathecally to verify the involvement of the opioid receptors in the antinociceptive effects of ginsenosides. Both ginsenosides and morphine produced antinociceptive effects in the formalin test. Isobolographic analysis revealed a synergistic interaction after intrathecal delivery of the ginsenosides-morphine mix. Intrathecal CTOP, naltrindole, and GNTI reversed the antinociceptive effects of ginsenosides. RT-PCR indicated that opioid receptors' mRNA was detected in spinal cord of naïve rats and the injection of formalin had no effect on the expression of opioid receptors' mRNA. Taken together, our results indicate synergistic antinociception following intrathecal coadministration of a ginsenosides/morphine mix in the formalin test, and that μ, δ, and κ opioid receptors are involved in the antinociceptive mechanism of ginsenosides.
  
  
  CONCLUSIONS
  This article concerns the antinociceptive activity of ginsenosides, which increases antinociception by morphine. Thus, a spinal combination of ginsenosides and morphine may be useful in the management of acute pain as well as facilitated state pain.
authors: Department of Anesthesiology and Pain Medicine, Chonnam National University, Medical School, Gwangju, Korea. mhyoon@chonnam.ac.kr
authors: Myung Ha
authors: MH
authors: Yoon
authors: Kwang Soo
authors: KS
authors: Kim
authors: Hyung Gon
authors: HG
authors: Lee
authors: Chang Mo
authors: CM
authors: Kim
authors: Woong Mo
authors: WM
authors: Kim
authors: Jeong Il
authors: JI
authors: Choi
authors: Yeo Ok
authors: YO
authors: Kim
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005404:Fixatives / Q000633:toxicity; D005557:Formaldehyde / Q000633:toxicity; D005786:Gene Expression Regulation / Q000187:drug effects; D036145:Ginsenosides / Q000008:administration & dosage*; D007278:Injections, Spinal / Q000379:methods; D008297:Male; D009020:Morphine / Q000627:therapeutic use*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000627:therapeutic use*; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D010147:Pain Measurement; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000235:genetics / Q000378:metabolism; D012018:Reflex / Q000187:drug effects; D013004:Somatostatin / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D005404:Fixatives; D036145:Ginsenosides; D009292:Narcotic Antagonists; D009294:Narcotics; D011957:Receptors, Opioid; C049352:phenylalanyl-cyclo(cysteinyltyrosyl-tryptophyl-ornithyl-threonyl-penicillamine)threoninamide; D005557:Formaldehyde; D009270:Naloxone; D013004:Somatostatin; D009020:Morphine