In 1680, Sydenham, a famous English physician, wrote, “Among the remedies which it has pleased Almighty God to give to man to relieve his sufferings, none is so universal and so efficacious as opium.” Following the isolation of morphine from opium almost 200 years ago and the invention of the hypodermic needle for parenteral application in the middle of the last century, this alkaloid became the remedy of choice for relief of severe pain – although its addictive properties also became more and more apparent. Thus, considerable efforts were undertaken to develop semisynthetic and synthetic derivates that might not be addictive. These attempts, however, were only partially successful.

A new era of opioid research began with the identification of opioid receptors and the detection of endogenous ligands of these receptors 25 years ago. Presently, the occurrence of three opioid receptor types (μ, δ, κ) is well established. They represent the targets of three families of opioid peptides, β-endorphin, enkephalins, and dynorphins. The wide distribution of these opioid receptors and ligands in the central and peripheral nervous systems and other organs points to multiple neuronal and extraneuronal functions. More recently, new opioid peptides and opioid receptor types have been detected, the functional significance of which is so far largely unknown. The recent cloning of opioid receptors will provide new insights into the function of these systems at the molecular level.

In parallel with these fundamental developments in the opioid field, major progress was also made with respect to the neurophysiologic and neurochemical mechanisms of acute and chronic pain.