PHARMACOLOGICAL STUDIES ON LAPPACONITINE - ANTINOCICEPTION AND INHIBITION OF THE SPINAL ACTION OF SUBSTANCE-P AND SOMATOSTATIN

The pain response of mice to an injection of 0.5% formalin into the dorsal surface of a hindpaw is biphasic, with a first phase lasting for 5 min and a second phase lasting from 10 to 30 min post-injection. Intrathecal (i.t.) injection of [D-Pro2, D-Trp7,9] - substance P inhibited the first phase,and i.t. cysteamine inhibited the second phase. Lappaconitine (LA) and morphine (MOR) inhibited both phases equally in a dose-dependent manner. Diclofenac inhibited both phases, but the second phase was inhibited by lower doses. An i.t. injection of substance P (SP) or somatostatin (SOM) produced a characteristic behavioral response (scratching, biting, and licking). This behavioral response to SP and SOM was inhibited by s.c., intracerebroventricular (i.c.v.), or i.t. injection of MOR. In contrast, LA inhibited the SP- and SOM-induced response when injected s.c. or i.c.v., but had no effect when injected intrathecally. These results indicate that LA may act supraspinally to inhibit the transmission of nociceptive information by SP and/or SOM.