Tissue injury and inflammation result in release of various mediators that promote ongoing pain or pain
hypersensitivity against mechanical, thermal and chemical stimuli. Pro-nociceptive mediators activate primary afferent
neurons directly or indirectly to enhance nociceptive signal transmission to the central nervous system. Excitation of
primary afferents by peripherally originating mediators, so-called “peripheral sensitization”, is a hallmark of tissue injuryrelated
pain. Many kinds of pro-nociceptive mediators, including ATP, glutamate, kinins, cytokines and tropic factors,
synthesized at the damaged tissue, contribute to the development of peripheral sensitization. In the present review we will
discuss the molecular mechanisms of peripheral sensitization following tissue injury.