Capsaicin activates the transient receptor potential vanilloid 1 receptor (TRPV1) on small sensory afferents, and capsaicin is commonly used to elucidate mechanisms of neuropathic pain. This study was performed to describe changes in cold and cold pain perception after topically applied capsaicin. Fourteen healthy subjects were included. Cold detection and cold pain thresholds and the response to suprathreshold cold stimuli were evaluated before and after topical application of capsaicin (200 microl, 50 mg/ml in 70% ethanol solution, 10.2 cm2) for 30 min. The skin temperature was kept between 34 and 35 degrees C. At the site of capsaicin application (the primary area), we found profound cold hypoesthesia and hypoalgesia, while outside the application site (the secondary area) there were no difference in the changes in cold detection and cold pain thresholds and cold-induced pain compared to the control arm. These results suggest a peripheral mediated decrease in cold sensation following TPRV1 receptor activation.