Abstract
Itch: its complex neurobiology, its exquisite evolutionary conservation, and even the undeniably euphoric sensation of the scratch it evokes, are all suggestive of a productive physiological function. Nevertheless, we still struggle to answer (or altogether overlook) the basic question of why we itch in the first place. Here, we propose a simple hypothesis: the purpose of itch sensation is to evoke scratching behavior, which in turn boosts protective immunity against the broad range of pathogenic challenges that enter at the skin. We propose that the key function of itch induced scratching is to physically disrupt the skin, serving as a “mechanical adjuvant” that amplifies and directs immune responses to the precise site of potential pathogen entry. As proof of principle, we show that the potent adjuvanticity of itch inducing Compound 48/80 is dependent on this agent’s ability to elicit scratching behavior.
