title: Anti-hypersensitive effect of intramuscular administration of αO-conotoxin GeXIVA[1,2] and GeXIVA[1,4] in rats of neuropathic pain.
abstract: αO-conotoxin GeXIVA (GeXIVA) is a potent antagonist of α9α10 nicotinic acetylcholine receptors (nAChRs), which has four Cys residues and three disulfide isomers. Among the 3 isomers, both GeXIVA[1,2] (bead isomer) and GeXIVA[1,4] (ribbon isomer) showed potent block on α9α10 nAChRs with close low nanomolar IC50s. Here we report that anti-hypersensitive effects of the bead and ribbon isomers in the chronic constriction injury (CCI) model of neuropathic pain and acute pain model of tail flick test. Treatment was started and continued for 7 or 14days after the development of hyperalgesia which was induced by CCI surgery. GeXIVA[1,2] and GeXIVA[1,4] significantly reduced mechanical allodynia in CCI rats without tolerance, in which GeXIVA[1,2] remained up to two weeks after intramuscular administration of the toxins was ceased. The pain reliever effect of GeXIVA[1,2] on neuropathic rats was slightly better than GeXIVA[1,4]. The two isomers did not suppress the acute thermal pain behaviors significantly when they were tested in the tail flick model by intramuscular bolus injection. Both GeXIVA[1,2] and GeXIVA[1,4] had no significant effect on performance of rats in the accelerating rotarod test after intramuscular injections. This suggests that αO-conotoxin GeXIVA[1,2] and GeXIVA[1,4] may offer new strategies to the treatment of neuropathic pain.
authors.affiliation: Key Laboratory of Tropical Biological Resources, Ministry of Education, Key Lab for Marine Drugs of Haikou, Hainan University, Haikou, Hainan 570228, China. Electronic address: lixiaodan816@163.com.
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Li
authors.affiliation: Key Laboratory of Tropical Biological Resources, Ministry of Education, Key Lab for Marine Drugs of Haikou, Hainan University, Haikou, Hainan 570228, China. Electronic address: 375896950@qq.com.
authors.forename: Yuanyan
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Key Laboratory of Tropical Biological Resources, Ministry of Education, Key Lab for Marine Drugs of Haikou, Hainan University, Haikou, Hainan 570228, China. Electronic address: wys211@163.com.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Key Laboratory of Tropical Biological Resources, Ministry of Education, Key Lab for Marine Drugs of Haikou, Hainan University, Haikou, Hainan 570228, China. Electronic address: 787961364@qq.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Key Laboratory of Tropical Biological Resources, Ministry of Education, Key Lab for Marine Drugs of Haikou, Hainan University, Haikou, Hainan 570228, China. Electronic address: 229449596@qq.com.
authors.forename: Shurun
authors.initials: S
authors.lastname: Yu
authors.affiliation: Key Laboratory of Tropical Biological Resources, Ministry of Education, Key Lab for Marine Drugs of Haikou, Hainan University, Haikou, Hainan 570228, China. Electronic address: 598594694@qq.com.
authors.forename: Qing
authors.initials: Q
authors.lastname: Ding
authors.affiliation: Key Laboratory of Tropical Biological Resources, Ministry of Education, Key Lab for Marine Drugs of Haikou, Hainan University, Haikou, Hainan 570228, China. Electronic address: zhangsundt@163.com.
authors.forename: Dongting
authors.initials: D
authors.lastname: Zhangsun
authors.affiliation: Key Laboratory of Tropical Biological Resources, Ministry of Education, Key Lab for Marine Drugs of Haikou, Hainan University, Haikou, Hainan 570228, China. Electronic address: luosulan2003@163.com.
authors.forename: Sulan
authors.initials: S
authors.lastname: Luo
mesh_terms: D000700:Analgesics / Q000627:therapeutic use*; D000818:Animals; D020916:Conotoxins / Q000627:therapeutic use*; D004195:Disease Models, Animal; D006930:Hyperalgesia / Q000188:drug therapy*; D008297:Male; D009437:Neuralgia / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000700:Analgesics; D020916:Conotoxins
keywords: Mechanical hyperalgesia; Neuropathic pain; Thermal pain; αO-Conotoxin GeXIVA[1,2]; αO-Conotoxin GeXIVA[1,4]