title: Zerumbone alleviates chronic constriction injury-induced allodynia and hyperalgesia through serotonin 5-HT receptors.
abstract: 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-HT1/6/7receptor antagonist, 0.1mg/kg), WAY-100635 (5-HT1Areceptor antagonist, 1mg/kg), isamoltane (5-HT1Breceptor antagonist, 2.5mg/kg), ketanserin (5-HT2Areceptor antagonist, 0.3mg/kg) and ondansetron (5-HT3receptor 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.
authors: Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia.
authors: Jasmine Siew Min
authors: JSM
authors: Chia
authors: Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia.
authors: Ahmad Akira
authors: AA
authors: Omar Farouk
authors: Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia.
authors: Azam Shah
authors: AS
authors: Mohamad
authors: Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia.
authors: Mohd Roslan
authors: MR
authors: Sulaiman
authors: Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia. Electronic address: enoch@upm.edu.my.
authors: Enoch Kumar
authors: EK
authors: Perimal
mesh_terms: D000818:Animals; D002908:Chronic Disease; D003250:Constriction; D020939:Zingiber officinale; D006930:Hyperalgesia / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009437:Neuralgia / Q000188:drug therapy*; D010936:Plant Extracts / Q000302:isolation & purification / Q000627:therapeutic use*; D011985:Receptors, Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000302:isolation & purification / Q000627:therapeutic use*; D012717:Sesquiterpenes / Q000302:isolation & purification / Q000627:therapeutic use*
chemical_list: D010936:Plant Extracts; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D012717:Sesquiterpenes; C403304:zerumbone
keywords: Neuropathic pain; Serotonin; Serotonin receptor; Zerumbone; Zingiber zerumbet