Evodiamine reduced peripheral hypersensitivity on the mouse with nerve injury or inflammation.

Management of chronic pain is still hard, and new analgesic drugs are needed. Evodiamine (Evo) and rutaecarpine (Rut) are two major active components of Evodia rutaecarpa, a Chinese traditional medicine that has been used as an analgesic for a long time. However, their effects on peripheral hypersensitivity remain unknown. Similar to capsaicin, the Evo and Rut were docked to the transient receptor potential cation channel subfamily V member 1 (TRPV1) in molecular simulation experiments. Moreover, Evo (10 mu M) and Rut (50 mu M) activated TRPV1 on human embryonic kidney 293 (HEK293) cells in electrophysiological recording experiments. Behaviorally, the application of Evo and Rut reduced peripheral hypersensitivity in a dose-dependent manner, which was blocked by capsazepine (a selective inhibitor of TRPV1). Furthermore, both Evo and Rut increased time in the open arms of the elevated plus maze on mice with nerve injury. These observations suggested that Evo and Rut reduced peripheral hypersensitivity and anxiety in mice with nerve injury or inflammation via TRPV1.