Our current research focuses on the capsaicin receptor TRPV1 ion channels and its homologs. Gating of these ion channels is “polymodal”, meaning that multiple physical and chemical stimuli can be simultaneously detected. Activation of TRPV1 by pungent compounds in chili peppers (capsaicin) and gingers (shogaol, gingerol, zingerone) produces the spicy sensation; its activation by heat supports temperature sensing and body thermo-regulation; its activation by extracellular H+ plays an important role in inflammation response. Activation of TRPV1 in nociceptive neurons by these and additional stimuli (e.g., toxins produced by venomous animals) initiates pain signaling. Multiple clinical trials are testing analgesic drug candidates that manipulate TRPV1 activity.