Activity in nociceptive nerve fibers does not only trigger the sensation of pain but it also starts a variety of nocifensive reflexes to protect the organism from the noxious agent. Some of these reflexes may, if active long enough, be harmful themselves, causing ischemia in visceral organs or other inadvertent reactions. Recently, several endogenous mechanisms have been discovered that can inhibit the transmission of nerve impulses from nociceptive afferents to other nerve cells, thus not only preventing the pain sensation but also modulating the nocifensive reflex responses. Several such mechanisms may involve the release of endorphins. These are small peptides, with opiate-like activity that were first discovered in 1975 by Hughes and Kosterlitz in Great Britain and by Terenius in Sweden. The distribution of such endorphins in the central nervous system was first investigated by Hökfelt and his coworkers. They found terminals and cell bodies containing endorphins in several areas of interest from the point of view of nociception. Thus the dorsal horn of the spinal cord, the corresponding area of the fifth cranial nerve and the periaqueductal gray matter contained such material.