Establishment of the estimation method for analgesia using stress-induced hyperalgesic animals

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1, The Kampo medicine Maoh-Bushi-Saishin -toh at peroral doses of 100 and 300 mg/kg produced an antinociception in rats and mice that showed hyperalgesia induced induced by repeated cold stress (RCS), without effect in healthy ones. Morphine (0.1-3 mg/kg, s.c.) and diclofenac (0.5-80 mg/kg, p.o.) also produced an antinociception in RCS animals.2, The antinociception of Maoh-Bushi-Saishin-toh (300 mg-kg, ) in the RCS rat was significantly suppressed by intrathecal pretreatment with the serotonergic neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) but not with the catecholaminergic neurotoxin, 6-hydroxydopamine (6-OHDA).3, The antiociception of Maoh-Bushi-Saishin-toh (300 mg/kg) in the RCS rat was significantly suppressed by intrathecal injection with antagonists for serotonin receptors, cyproheptadine, methiotepine and methysergide, but not with an antagonist for adrenaline receptors, phentolamine.4, The Kampo medicine Keishi-toh at peroral doses of 100 and 300 mg-kg produced an antinociception in rats that showed hyperalgesia induced by RCS,without effect in healthy ones.5, The intrathecal pretreatment with 6-OHDA tended to suppress the antinociception of Keishi-toh (300 mg/kg) in the RCS rat, but 5,7-DHT had no effect on the antinociception of Keishi-toh.6, As mentioned above, we detected antinociceptive effects of Maoh-Bushi-Saishin-toh and Keishi-toh using RCS-induced hyperalgesic animals. In addition, these findings suggest that the antinociception of Maoh-Bushi-Saishin-toh and Keishi-toh may be at least in part mediated by the descending serotonergic and the descending noradrenergic systems, respectively.