Heat is often used for pain relief but basic information related to the potential mechanisms are not well understood in humans. This manuscripts reviews clinical studies of heat induced pain relief in humans, analyses basic laboratory studies, and offers possible mechanisms of action based on these animal findings particularly as related to TRPV1 channels. Many of the laboratory studies done on TRPV1 channels likely have strong correlations in humans. Recent human studies are discussed that provide insights on onset of action, duration of pain relief, and relationship of thermal energy delivered to analgesic effect with correlation to these laboratory findings.

The term analgesic nociceptive boundary is offered to describe the amount of thermal energy needed to cause maximal pain relief while not causing nociception or tissue damage. This boundary provides a framework for future clinical development.