Effects of central Ca2+ on analgesic action of lappaconitine

Lappaconitine (LA), isolated from Aconitum sinomontanum Nakai, was characterized as analgesic principle by our laboratory. The analgesic effect of ip LA 6 mg/kg as measured in the rat tail-flick test was reduced by icv CaCl2 or MgCl2 0.1 or 1 mumol/rat. BaCl2 was inactive. The analgesic action induced by LA was potentiated by ethylene glycol tetraacetic acid (EGTA, 0.2 mumol/rat icv) but not by ethylenediamine tetraacetic acid (EDTA, 0.2 or 0.4 mumol/rat icv). The calcium antagonists nifedipine (5 mg/kg ip) and verapamil (1 mumol/rat icv) partially reversed the Ca2+ antagonistic effect on LA analgesia, although nifedipine did not enhance LA analgesic action and only at 15 min after medication did verapamil exhibit enhancement of LA analgesia. The analgesic activity of LA was reduced and augmented by microinjection of CaCl2 0.5 mumol and EGTA 50 nmol to periaqueductal gray (PAG) area, respectively. These results suggest that LA can produce analgesia, possibly through a decrease in cellular calcium availability and PAG may be involved in the Ca2+ antagonistic effect on LA analgesia.