Transient receptor potential channels and itch: how deep should we scratch?

Over the past 30 years, transient receptor potential (TRP) channels have evolved from a somewhat obscure observation on how fruit flies detect light to become the center of drug discovery efforts, triggering a heated debate about their potential as targets for therapeutic applications in humans. In this review, we describe our current understanding of the diverse mechanism of action of TRP channels in the itch pathway from the skin to the brain with focus on the peripheral detection of stimuli that elicit the desire to scratch and spinal itch processing and sensitization. We predict that the compelling basic research findings on TRP channels and pruritus will be translated into the development of novel, clinically useful itch medications.