Positive Allosteric Modulators Transient receptor potential vanilloid 1 (TRPV1) ion channel is critically involved in pain sensation. Positive allosteric modulators (PAMs) of TRPV1 are de novo designed based on the structure of TRPV1. Surface plasmon resonance and patch‐clamp recording demonstrate that the PAMs bind to TRPV1 and allosterically enhance its activities. The PAM exhibits analgesic effects without changing body temperature in rats. More details can be found in article number 2101716 by Yuhua Tian, Jie Zheng, Fan Yang, and co‐workers.