Na v1. 9 voltage-gated sodium channel is preferentially expressed in peripheral nociceptive neurons. Recent progresses have proved its role in pain sensation, but our understanding of Na v1.9, in general, has lagged behind because of limitations in heterologous expression in mammal cells. In this work, functional expression of human Na v1.9 (hNa v1.9) was achieved by fusing GFP to the C-terminal of hNa v1.9 in ND7/23 cells, which has been proved to be a reliable method to the electrophysiological and pharmacological studies of hNa v1.9. By using the hNa v1.9 expression system, we investigated the electrophysiological properties of four mutations of hNa v1.9 (K419N, A582T, A842P, and F1689L), whose electrophysiological functions have not been determined yet. The four mutations significantly caused positive shift of the steady-state fast inactivation and therefore increased hNa v1.9 activity, consistent with the phenotype of painful peripheral neuropathy. Meanwhile, the effects of inflammatory mediators on hNa v1.9 were also investigated. Impressively, histamine was found for the first time to enhance hNa v1.9 activity, indicating its vital role in hNa v1.9 modulating inflammatory pain. Taken together, our research provided a useful platform for hNa v1.9 studies and new insight into mechanism of hNa v1.9 linking to pain.