Effects of processed Aconiti tuber and its ingredient alkaloids on the development of antinociceptive tolerance to morphine

• Published in: Journal of ethnopharmacology 2006-02, Vol.103 (3), p.398-405
• Main Authors: Shu, Haihua, Arita, Hideko, Hayashida, Masakazu, Sekiyama, Hiroshi, Hanaoka, Kazuo
• Format: Article
• Language: English
• Subjects: Aconitine; Aconitine - analogs & derivatives; Aconitine - isolation & purification; Aconitine - pharmacology; Aconitine - therapeutic use; Aconitum; Aconitum - chemistry; alkaloids; Alkaloids - isolation & purification; Alkaloids - pharmacology; Alkaloids - therapeutic use; analgesic effect; Analgesics - isolation & purification; Analgesics - pharmacology; Analgesics - therapeutic use; Analgesics, Opioid - pharmacology; Analgesics, Opioid - therapeutic use; Animals; Biological and medical sciences; chemical constituents of plants; Dose-Response Relationship, Drug; Drug Tolerance; Drugs, Chinese Herbal - pharmacology; Drugs, Chinese Herbal - therapeutic use; ethnobotany; General pharmacology; herbal medicines; Hypaconitine; Kappa-opioid receptor; Male; Medical sciences; medicinal plants; medicinal properties; Mesaconitine; Mice; morphine; Morphine - pharmacology; Morphine - therapeutic use; Morphine tolerance; Oriental traditional medicine; Pain - drug therapy; Pain Measurement; Pain Threshold - drug effects; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; plant extracts; Plant Tubers; Processed Aconiti tuber; Time Factors; tubers
• ISSN: 0378-8741; 1872-7573
• DOI: 10.1016/j.jep.2005.08.017

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.