Zerumbone, a bioactive
sesquiterpene isolated from Zingiber zerumbet (Smith), has shown to exert antiallodynic and antihyperalgesic effects in
neuropathic pain mice model in our recent study. The mechanism through which
zerumbone alleviates
neuropathic pain has yet to be elucidated. Thus, this study aimed to determine whether the serotonergic system, part of the descending
pain modulation pathway, contributes to the antineuropathic effect of
zerumbone. Participation of the serotonergic system in
zerumbone-induced antiallodynia and antihyperalgesia was assessed using Dynamic Plantar Aesthesiometer von Frey test and Hargreaves plantar test respectively in chronic-constriction injury mice model. Administration of ρ-chlorophenylalanine (PCPA, 100mg/kg, i.p.) for four consecutive days to deplete
serotonin (5-HT) prior to
zerumbone administration blocked the antiallodynic and antihyperalgesic effects of
zerumbone. Further investigation with
5-HT receptor antagonists
methiothepin (5-HT1/6/7 receptor antagonist, 0.1mg/kg),
WAY-100635 (
5-HT1A receptor antagonist, 1mg/kg),
isamoltane (
5-HT1B receptor antagonist, 2.5mg/kg),
ketanserin (
5-HT2A receptor antagonist, 0.3mg/kg) and
ondansetron (
5-HT3 receptor antagonist, 0.5mg/kg) managed to significantly attenuate antiallodynic and antihyperalgesic effects of
zerumbone (10mg/kg). These findings demonstrate that
zerumbone alleviates
mechanical allodynia and
thermal hyperalgesia through the descending serotonergic system via
5-HT receptors 1A, 1B, 2A, 3, 6 and 7 in chronic constriction injury
neuropathic pain mice.