title: Synthesis and analgesic effects of μ-TRTX-Hhn1b on models of inflammatory and neuropathic pain.
abstract: μ-TRTX-Hhn1b (HNTX-IV) is a 35-amino acid peptide isolated from the venom of the spider, Ornithoctonus hainana. It inhibits voltage-gated sodium channel Nav1.7, which has been considered as a therapeutic target for pain. The goal of the present study is to elucidate the analgesic effects of synthetic μ-TRTX-Hhn1b on animal models of pain. The peptide was first synthesized and then successfully refolded/oxidized. The synthetic peptide had the same inhibitory effect on human Nav1.7 current transiently expressed in HEK 293 cells as the native toxin. Furthermore, the analgesic potentials of the synthetic peptide were examined on models of inflammatory pain and neuropathic pain. μ-TRTX-Hhn1b produced an efficient reversal of acute nociceptive pain in the abdominal constriction model, and significantly reduced the pain scores over the 40-min period in the formalin model. The efficiency of μ-TRTX-Hhn1b on both models was equivalent to that of morphine. In the spinal nerve model, the reversal effect of μ-TRTX-Hhn1b on allodynia was longer and higher than mexiletine. These results demonstrated that μ-TRTX-Hhn1b efficiently alleviated acute inflammatory pain and chronic neuropathic pain in animals and provided an attractive template for further clinical analgesic drug design.
authors.affiliation: College of Chemistry and Chemical Engineering, Hunan Institute of Science and Technology, Yueyang 414006, Hunan, China. hiliu2000@126.com.
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.affiliation: The Second Xiangya Hospital of Central South University, Changsha 410008, Hunan, China. tjg168@aliyun.com.
authors.forename: Jianguang
authors.initials: J
authors.lastname: Tang
authors.affiliation: College of Life Sciences, Hunan Normal University, Changsha 410081, Hunan, China. yunxiao_zhang@126.com.
authors.forename: Yunxiao
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: College of Chemistry and Chemical Engineering, Hunan Institute of Science and Technology, Yueyang 414006, Hunan, China. xiaohongxun2012@126.com.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Xun
authors.affiliation: College of Chemistry and Chemical Engineering, Hunan Institute of Science and Technology, Yueyang 414006, Hunan, China. tdfyouxiang@126.com.
authors.forename: Dongfang
authors.initials: D
authors.lastname: Tang
authors.affiliation: College of Chemistry and Chemical Engineering, Hunan Institute of Science and Technology, Yueyang 414006, Hunan, China. pdz29167641@163.com.
authors.forename: Dezheng
authors.initials: D
authors.lastname: Peng
authors.affiliation: College of Chemistry and Chemical Engineering, Hunan Institute of Science and Technology, Yueyang 414006, Hunan, China. yjm91@163.com.
authors.forename: Jianming
authors.initials: J
authors.lastname: Yi
authors.affiliation: College of Life Sciences, Hunan Normal University, Changsha 410081, Hunan, China. liuzh@hunnu.edu.cn.
authors.forename: Zhonghua
authors.initials: Z
authors.lastname: Liu
authors.affiliation: The Second Xiangya Hospital of Central South University, Changsha 410008, Hunan, China. xiaoliushi@aliyun.com.
authors.forename: Xiaoliu
authors.initials: X
authors.lastname: Shi
mesh_terms: D019342:Acetic Acid; D000700:Analgesics / Q000138:chemical synthesis / Q000627:therapeutic use*; D000818:Animals; D004195:Disease Models, Animal; D005557:Formaldehyde; D057809:HEK293 Cells; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D008297:Male; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects; D062556:NAV1.7 Voltage-Gated Sodium Channel / Q000502:physiology; D009437:Neuralgia / Q000139:chemically induced / Q000188:drug therapy*; D010455:Peptides / Q000138:chemical synthesis / Q000627:therapeutic use*; D017207:Rats, Sprague-Dawley; D013111:Spider Venoms / Q000138:chemical synthesis / Q000627:therapeutic use*; D013127:Spinal Nerves / Q000293:injuries; D061567:Voltage-Gated Sodium Channel Blockers / Q000138:chemical synthesis / Q000627:therapeutic use*
chemical_list: D000700:Analgesics; D062556:NAV1.7 Voltage-Gated Sodium Channel; D010455:Peptides; C486866:SCN9A protein, human; D013111:Spider Venoms; D061567:Voltage-Gated Sodium Channel Blockers; C474037:hainantoxin-IV, Seleconosmia hainana; D005557:Formaldehyde; D019342:Acetic Acid