Mechanisms Involved in the Antinociceptive Effect in Mice of the Hydroalcoholic Extract of Siphocampylus verticillatus

The antinociception caused by the hydroalcoholic extract of Siphocampylus verticillatus (Campanulaceae) has been investigated in chemical and thermal models of nociception in mice. We have also assessed some of the mechanisms underlying the antinociceptive effect of the extract. The hydroalcoholic extract of S. verticillatus (60–1000 mg kg^?1, i.p. or p.o.) produced dose-related, significant and long-lasting (6 to 8 h) inhibition of acetic acid-induced abdominal constriction in mice, with ID50 values of 204 and ～1000 mg kg^?1, respectively. In the formalin test, the extract (100–1000 mg kg^?1), given either intraperitoneally or orally, resulted in graded inhibition of both phases of formalin-induced pain, being about 2- to 4-fold more potent in attenuating the second phase of the pain. The calculated mean ID50 (mg kg^?1) values for the earlier and the later phases were: 491 and 186 and 640 and 441, respectively. In addition, the extract (60–1000 mg kg^?1, i.p. or p.o.) caused marked and dose-related inhibition of capsaicin-induced neurogenic pain with mean ID50 values of 420 and 485 mg kg^?1, respectively. The hydroalcoholic extract, at the same doses, did not significantly affect the performance of animals in the rota-rod test, nor did it have any analgesic effect in the tail-flick or hot-plate tests. The treatment of animals with naloxone (5 mg kg^?1, s.c.) significantly reversed the analgesic effect of both morphine (5 mg kg^?1, s.c.) and the extract (300 mg kg^?1, i.p.) when assessed against acetic acid-induced abdominal constrictions. The treatment of animals with l-arginine (600 mg kg^?1, i.p.) significantly attenuated the antinociceptive effects of N^G-nitro-l-arginine (l-NOARG) (75 mg kg^?1, i.p.), of the hydroalcoholic extract (600 mg kg^?1, i.p.) or of morphine (5 mgkg^?1, s.c.), when analysed against the formalin test. In addition, adrenalectomy of animals 7 days before the tests significantly reversed the antinociception caused by the hydroalcoholic extract (300 mg kg^?1, i.p.) in the formalin-induced pain. These data show that the hydroalcoholic extract of S. verticillatus has significant and long-lasting oral antinociception when assessed against both neurogenic and inflammatory models of nociception in mice. The precise mechanism responsible for the analgesic effect of the extract still remains unclear, but a great part of this effect seems to be partly related to an opioid-like action and involvement of the l-arginine-nitric oxide pathway. Finally, the antinociception caused by the hydroalcoholic extract of S. verticillatus is modulated by adrenal hormones.