HNTX-III Alleviates Inflammatory and Neuropathic Pain in Animal Models

Voltage-gated sodium channel plays a critical role in pain sensation and has been considered as a potential target for the development of analgesic drug. Hainantoxin-III(HNTX-III) is a selective inhibitor of neuronal tetrodotoxin-sensitive voltage-gated sodium channels with similar selectivity for Nav1.7, 1.2 and 1.3 but not for Nav1.4 and Nav1.5 from the venom of the spider O. hainana . The aim of the present study is to investigate the analgesic effect of HNTX-III on inflammatory and neuropathic pain models. In the complete Freund’s adjuvant (CFA) model and formalin model of inflammatory pain, HNTX-III produced reversal of hyperalgesia comparable with morphine, and in the spared nerve injury model of pain, HNTX-III inhibited allodynia compared with mexiletine. HNTX-III was also evaluated in a motor coordination assay to assess its propensity for central nervous system side effects, indicating it did not induce impairment of motor coordination. Our findings revealed that HNTX-III significantly alleviated chronic neuropathic pain and acute inflammatory pain and provided a potential template for analgesic drug design in future.