Yuji Omiya, Kazuhiro Goto, Yasuyuki Suzuki, Atsushi Ishige and Yasuhiro
Komatsu
Kampo and Pharmacognosy Laboratories, Tsumura & Co., 3586 Yoshiwara,
Ami-machi, Ibaraki 300-1192, Japan
Abstract: 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.
Keywords: Processed Aconiti tuber, Antinociception, Dynorphin, Spinal
cord, Hypothalamic arcuate nucleus