High doses of processed Aconiti tuber inhibit the acute but potentiate the chronic antinociception of morphine.
OBJECTIVE
In this study, we investigated the effects of processed Aconiti tuber (PAT), an oriental herbal medicine, at analgesic doses on acute morphine antinociception in morphine-naïve mice and morphine tolerance in morphine-tolerant mice.


METHODS
In acute experiments, mice received subcutaneous (s.c.) morphine (2, 5, or 10 mg/kg) and oral distilled water or PAT (0.3, 1.0, or 3.0 g/kg). The mechanical nociceptive threshold (MNT) and thermal nociceptive latency (TNL) were measured with the tail pressure test and tail flick test, respectively, before, and at 30, 60, 90, and 120 min after s.c. morphine injection. In chronic experiments, mice received s.c. morphine (10 mg/kg) and oral distilled water or PAT (0.3, 1.0, or 3.0 g/kg) once daily for 11 days. MNT was measured before, and at 60 min after, and TNL was measured before, and at 30 min after, daily morphine injections on days 1-11.


RESULTS
PAT at analgesic doses inhibited the acute antinociceptive effect of morphine dose-dependently in morphine-naïve mice. In contrast, PAT at analgesic doses potentiated the chronic antinociceptive effect of morphine dose-dependently by inhibiting the development of morphine tolerance dose-dependently. These effects of PAT on acute and chronic morphine antinociception were mediated through activation of kappa-opioid receptors.


CONCLUSIONS
These results indicated that chronic co-administration of PAT at analgesic doses with morphine could provide better-maintained morphine analgesia in a long-term morphine treatment after initial inhibition of acute morphine antinociception for a brief period of time.
Shu
Haihua
H
Department of Anesthesiology, First Affiliated Hospital of Sun Yat-Sen University, 58# Zhongshan 2nd Road, Guangzhou 510080, PR China. shuhaihua@hotmail.com
Hayashida
Masakazu
M
Arita
Hideko
H
Huang
Wenqi
W
Xiao
Liangshan
L
Chiba
Shunsuke
S
Sekiyama
Hiroshi
H
Hanaoka
Kazuo
K
D031841:Aconitum / Q000737:chemistry*; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004347:Drug Interactions; D004361:Drug Tolerance; D008297:Male; D008518:Medicine, East Asian Traditional; D051379:Mice; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects*; D035281:Plant Tubers; D017473:Receptors, Opioid, kappa / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors
D000701:Analgesics, Opioid; D017473:Receptors, Opioid, kappa; D009020:Morphine