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.