Analgesia-producing mechanism of processed Aconiti tuber: role of dynorphin, an endogenous kappa-opioid ligand, in the rodent spinal cord.
The analgesia-producing mechanism of processed Aconiti tuber was examined using rodents whose nociceptive threshold was decreased by loading repeated cold stress (RCS). The antinociceptive effect of processed Aconiti tuber (0.3 g/kg, p.o.) in RCS-loaded mice was antagonized by pretreatment with a kappa-opioid antagonist, nor-binaltorphimine (10 mg/kg, s.c.), and was abolished by an intrathecal injection of anti-dynorphin antiserum (5 microg). The Aconiti tuber-induced antinociception was inhibited by both dexamethasone (0.4 mg/kg, i.p.) and a dopamine D2 antagonist, sulpiride (10 mg/kg, i.p.), in RCS-loaded mice, and it was eliminated by both an electric lesion of the hypothalamic arcuate nucleus (HARN) and a highly selective dopamine D2 antagonist, eticlopride (0.05 microg), administered into the HARN in RCS-loaded rats. These results suggest that the analgesic effect of processed Aconiti tuber was produced via the stimulation of kappa-opioid receptors by dynorphin released in the spinal cord. It was also shown that dopamine D2 receptors in the HARN were involved in the expression of the analgesic activity of processed Aconiti tuber.
Omiya
Y
Y
Kampo Laboratories, Tsumura & Co., Ibaraki, Japan.
Goto
K
K
Suzuki
Y
Y
Ishige
A
A
Komatsu
Y
Y
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology; D000287:Administration, Topical; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000473:pathology / Q000503:physiopathology; D003080:Cold Temperature; D003907:Dexamethasone / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004399:Dynorphins / Q000276:immunology / Q000502:physiology; D005938:Glucocorticoids / Q000494:pharmacology; D007031:Hypothalamus / Q000473:pathology / Q000503:physiopathology; D007106:Immune Sera / Q000276:immunology / Q000494:pharmacology; D008024:Ligands; D008297:Male; D051379:Mice; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects; D010146:Pain / Q000188:drug therapy / Q000503:physiopathology; D017288:Pain Threshold / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors; D017473:Receptors, Opioid, kappa / Q000502:physiology; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors; D012457:Salicylamides / Q000494:pharmacology; D013116:Spinal Cord / Q000187:drug effects / Q000503:physiopathology; D013469:Sulpiride / Q000494:pharmacology
D000700:Analgesics; D018492:Dopamine Antagonists; D004365:Drugs, Chinese Herbal; D005938:Glucocorticoids; D007106:Immune Sera; D008024:Ligands; D009292:Narcotic Antagonists; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D012457:Salicylamides; C051844:norbinaltorphimine; D009271:Naltrexone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; C024524:beta-funaltrexamine; D004399:Dynorphins; D013469:Sulpiride; D003907:Dexamethasone; C055382:naltrindole; C045989:eticlopride