title: Effects of processed Aconiti tuber and its ingredient alkaloids on the development of antinociceptive tolerance to morphine.
abstract: Processed Aconiti tuber (PAT) is a herbal medicine that has been widely used as an analgesic since ancient times. We investigated effects of subanalgesic doses of PAT on morphine tolerance in mice. Mice received subcutaneous morphine (10 mg/kg) and oral PAT at subanalgesic doses (0.1 or 0.3 g/kg), once a day for 7 days. Mechanical nociceptive thresholds were measured using the tail pressure test, at 60 min after the daily s.c. morphine injections. In the placebo-treated group, repeated administration of s.c. morphine resulted in development of analgesic tolerance. In the PAT-treated groups, oral PAT attenuated morphine tolerance, dose-dependently. The main ingredient alkaloid of PAT causing its tolerance-attenuating activity was mesaconitine, but other ingredient alkaloids, such as aconitine and hypaconitine, also contributed to this activity. In addition, repeated treatment with PAT could reverse already-developed morphine tolerance. Subanalgesic doses of oral PAT thus can attenuate and reverse morphine tolerance in mice.
authors.affiliation: Department of Anesthesiology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
authors.forename: Haihua
authors.initials: H
authors.lastname: Shu
authors.forename: Hideko
authors.initials: H
authors.lastname: Arita
authors.forename: Masakazu
authors.initials: M
authors.lastname: Hayashida
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sekiyama
authors.forename: Kazuo
authors.initials: K
authors.lastname: Hanaoka
mesh_terms: D000157:Aconitine / Q000031:analogs & derivatives / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D031841:Aconitum / Q000737:chemistry*; D000470:Alkaloids / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D000700:Analgesics / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D000701:Analgesics, Opioid / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D004365:Drugs, Chinese Herbal / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology* / Q000627:therapeutic use; D010146:Pain / Q000188:drug therapy; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects*; D035281:Plant Tubers; D013997:Time Factors
chemical_list: D000470:Alkaloids; D000700:Analgesics; D000701:Analgesics, Opioid; D004365:Drugs, Chinese Herbal; C088301:tsumura-shuchi-bushi-matsu; C058309:hypaconitine; C019470:mesaconitine; D009020:Morphine; D000157:Aconitine