Study On The Analgesic Activity Of α*-conotoxin [S9K]TxID And GeXIVA[1,2]

Pain has been listed as the fifth vital sign after respiration,pulse,blood pressure and temperature by modern medicine,which seriously affects the quality of life of patients.At present,the drugs in clinical treatment of neuropathic pain and inflammatory pain have obvious side effects and poor therapeutic effect,so there is an urgent need for novel analgesics.Previous studies have shown thatα3β4 n ACh R andα9α10 n ACh R are involved in the regulation of pain,and their antagonists can alleviate neuralgia.α-Conotoxin[S9K]TxID and GeXIVA[1,2]inhibit theα3β4 n ACh R(IC₅₀=6.9 n M)andα9α10n ACh R(IC₅₀=3.8 n M)separately,which can be used as molecular probes for studying the structure and function ofα3β4 andα9α10 n ACh Rs and is expected to be developed as drugs or lead compounds for the treatment of pain.The purpose of this study is to investigate the analgesic activity ofα-conotoxin[S9K]TxID and GeXIVA[1,2]on different types of pain models,such as physiological pain,inflammatory pain and neuralgia.The results showed that[S9K]TxID produced obvious analgesic activity in mice by intrathecal administration（P<0.001）.For plantar incision model,a single intrathecal injection of 0.96 mg/kg and 0.19 mg/kg[S9K]TxID could produce significant and dose-dependent analgesic activity（P<0.001）in plantar incision model,and the analgesic effect of 0.96 mg/kg of[S9K]TxID was longer lasting comparing to morphine group.For SNI model,a single intrathecal injection of 0.96 mg/kg[S9K]TxID has obvious analgesic activity（P<0.001）.For CFA model,high-dose[S9K]TxID（0.96mg/kg）did not show analgesic activity.In the tail flick test,compared with the saline group,the tail flick latency of[S9K]TxID mice did not change significantly,indicating that it did not affect physiological pain.In addition,the open filed test showed that[S9K]TxID had no effect on the exercise ability of normal mice.GeXIVA[1,2]displayed analgesic activity in mice of plantar incision and CFA models;while has no obvious analgesic effect for formalin-induced acute inflammatory pain.The mechanism of[S9K]TxID and GeXIVA[1,2]producing analgesic effects still needs further research,which lay a foundation for the development of original new analgesics.