Capsaicin

Capsaicin is the naturally occurring irritant compound found in chili peppers (especially in the seeds) that results in their spicy, pungent flavor. The evolution of this chemical in plants protected them from being eaten by animals by causing a painful sensation of heat when in contact with mucous membranes. An investigation into capsaicin's mechanism of action found that it activates the TRPV1 channel present on specific types of neurons, including those sensitive to heat. Capsaicin binds to and stabilizes the open conformation of the TRPV1 channel receptor, triggering an action potential. For this reason, capsaicin is often used in pain research to mimic pain by triggering the activation of nociceptors.

Figure 1. Structure of capsaicin with the head highlighted in red and the tail highlighted in blue.

Some people thoroughly enjoy the taste and experience of capsaicin at small or even large doses. However, high enough levels of capsaicin will eventually be painful to all humans. Capsaicin is a unique irritant in that it causes a refractory period in neurons after the initial excitation allowing it to also be used therapeutically (and slightly counter-intuitively) to reduce chronic pain in various painful conditions.