The transient receptor potential vanilloid 1 (TRPV1) is a polymodal ion channel activated by capsaicin, protons, and heat. It is predominantly expressed in the peripheral endings of small-diameter nociceptive primary afferent neurons. The localization of TRPV1 receptors in nociceptors and their ability to integrate harmful physical and chemical irritants, as well as inflammation mediators, make them important phar - macological targets for pain therapy. This study aimed to assess the effect of the novel TRPV1 receptor antagonist, AMG-517, on the activation of sensitive nociceptive skin endings by capsaicin and heat. For this, we recorded the activity of single afferents in mouse n. saphenous-skin preparation. AMG-517 al- most completely blocked responses of nerve fibers to the application of selective TRPV1 receptor agonist capsaicin (20 µmol/l), but did not affect the activation in response to temperature increase (50°C). The obtained results suggest significant pharmacological differences between cellular nociception models, such as spinal ganglion neurons and transfected cell lines, and native nerve endings. Thus, TRPV1 is not the only thermally activated sensor for heat responsiveness of cutaneous nociceptors.