TRPV1 channels and the progesterone receptor Sig-1R interact to regulate pain

Significance The TRPV1 ion channel has been widely associated with the generation of painful responses. The responses of cells expressing this ion channel and, presumably, the overall pain response of an organism may be regulated by controlling the amount of TRPV1 channels in the plasma membrane. TRPV1 levels can be regulated by its interaction with intracellular proteins, but there are no studies describing TRPV1 or any other mammalian TRP channel’s association with chaperones or how these interactions may affect the perception of pain. Here, we show that TRPV1-dependent pain is decreased through Sig-1R antagonism by progesterone and determine the presence of a physical interaction between these two proteins that may reduce pain under physiological conditions such as pregnancy.