Schematic drawing of a sensory ending of a nociceptor in the tissue. The membrane at the bottom shows ion channels for transduction (which produce a sensor potential, SP), a voltage-gated Na+ channel for the generation of action potentials (APs), and voltage-gated K+ and Ca2+ channels that control excitability. The other part of the membrane displays receptors for mediators that act on different second messenger systems. Classical inflammatory mediators are bradykinin, prostaglandin E2, 5-hydroxytryptamine, and histamine. ASIC, acid-sensing ion channel; PTX, purinergic ion channel; TRP, transient receptor potential.