n-deacetyllappaconitine and Pain

The effects of lappaconitine (LA) and N-deacetyllappaconitine (DLA) on footshock-induced analgesia (FSIA) were studied by the rat tail flick test. Rats subjected to 90 s nonescaping footshock had a significant increase in tail flick latency. Naloxone (4 micrograms, i.c.v.) partially antagonized the FSIA. After 5 consecutive exposures to footshock, rats developed a complete tolerance to the FSIA. The rats tolerant to FSIA showed a cross-tolerance to morphine- but not LA- and DLA-induced analgesia. Administrations of subanalgesic doses of LA and DLA potentiated the FSIA in both intact and adrenalectomized rats.

Topics: Aconitine; Adrenalectomy; Analgesics; Animals; Drug Synergism; Drug Tolerance; Naloxone; Pain; Rats; Rats, Inbred Strains

In the rat tail flick test, ip LA 6 mg/kg, icv DLA 60 micrograms and icv or with morphine 5 micrograms exhibited significant analgesia. But with either LA 40 micrograms or DLA 60 micrograms was inactive. Naloxone (4 micrograms icv) which antagonized morphine analgesia failed to alter the analgesia induced by LA and DLA. Microinjection of DLA 20 micrograms or morphine 5 micrograms into the periaqueductal gray (PAG) or nucleus raphe magnus (NRM) produced markedly analgesic activity. The effects of electrolytic and kainic acid (0.8 micrograms) lesions of the PAG and NRM on the analgesia elicited in the rat from ip LA, icv DLA and morphine were also evaluated. No change in baseline tail flick latency was observed following lesions of the PAG and NRM. But lesions of the PAG and NRM significantly attenuated the analgesia mediated by LA, DLA and morphine. These results suggest that supraspinal sites, especially the PAG and NRM, are involved in the analgesic action induced by LA, DLA and morphine.

Topics: Aconitine; Analgesia; Animals; Male; Morphine; Pain; Periaqueductal Gray; Raphe Nuclei; Rats; Sensory Thresholds

In the rat tail-flick test it was shown that ip lappaconitine (LA) 1-6 mg/kg, N-deacetyllappaconitine (DLA) 4-10 mg/kg or icv DLA 20-60 micrograms/rat exhibited a dose-dependent analgesic activity, but icv LA 20-40 micrograms/rat was inactive. The analgesic potency of ip LA was a little more potent than that of DLA and slightly weaker than that of morphine (P less than 0.05). Combined ip of subanalgesic doses of morphine and LA or DLA produced significant analgesic action. Analgesia mediated by LA was not antagonized by naloxone. The analgesic effect induced by LA or DLA was abolished and restored 3 and 120 h, respectively, after ip reserpine 3 mg/kg. Concomitant administration of 1-tryptophan or 5-HT as well as premedication of alpha-methyldopa prevented reserpine-induced decrease on LA or DLA analgesia. The elevation of brain 5-HT level by icv 5-HT significantly enhanced the analgesia of LA and DLA. LA- or DLA-induced analgesia was attenuated by pretreatment of p-chlorophenylalanine but this attenuation was reversed by icv 5-HT. p-Chloroamphetamine also markedly reduced LA- or DLA-induced analgesia. It is concluded that the central serotoninergic system is involved in the modulation of LA- or DLA-induced analgesia.

Topics: Aconitine; Aconitum; Animals; Anti-Inflammatory Agents, Non-Steroidal; Female; Male; Morphine; Pain; Rats; Reserpine; Sensory Thresholds; Serotonin