REVIEW Capsaicin selectively binds to a protein known as TRPV1, which resides on the membranes of pain- and heat-sensing neurons. TRPV1 is a heat-activated calcium channel, with a threshold to open between 37°C and 45°C (37°C is normal body temperature). When capsaicin binds to TRPV1, it causes the channel to lower its opening threshold, thereby opening it at temperatures less than the body's temperature, which is why capsaicin is linked to the sensation of heat. As mentioned earlier, prolonged activation of these neurons by capsaicin depletes presynaptic substance P, one of the body's neurotransmitters for pain and heat, and prevents reaccumulation. Neurons that do not contain TRPV1 are unaffected; this causes extended numbness following surgery, and the patient does not feel pain as the capsaicin is applied under anesthesia.
Nelson AJ, Ragan BG, Bell GW, et al. Capsaicin-based analgesic balm decreases pressor responses evoked by muscle afferents. Med Sci Sports Exerc. 2004;36(3):444-450.