The 2021 Nobel Prize in physiology or medicine was awarded to David Julius and Ardem Patapoutian, based on the outstanding contributions in temperature receptors TRPV1 and tactile receptors PIEZO1/PIEZO2, respectively. They elucidated the mechanisms underlying how the human nervous system senses cold/heat and mechanical stimulation, which contributes to the development of drugs for long-term pain. This article reviews David Julius’ pioneering work on TRPV1 which can be activated by capsaicin, heat (>43℃), H⁺ (pH<6.0), and the critical roles of TRPV1 participating in cancer pain, chronic inflammatory pain, neuropathic pain, and visceral pain by inducing peripheral and/or central sensitization.