The endogenous opioids are a large family of neuropeptides widely distributed throughout the central and peripheral nervous systems. These neurotransmitters are crucial to the normal functioning of important processes such as motor coordination, learning and memory, gastrointestinal function, the control of seizures, and the hormonal regulation of the reproductive system, yet they are most often recognized for their central role in the modulation of pain. Opiate pain-killers such as Morphine and Demorol, as well as narcotic street drugs like Heroin, act at the receptors for these neuropeptide neurotransmitters. In fact, opium derivatives were used for centuries in the treatment of pain before the mechanism behind their analgesic effect was ever understood. Once it was discovered that these chemicals work at specific receptor sites in the body, it was proposed that our bodies must naturally produce chemicals that are similar in nature and action. The endogenous opioids were subsequently isolated and named to reflect the amazing ability of our bodies to produce its own painkillers. These neuropeptides are often referred to as endorphins, endo- derived from "endogenous," and -orphin derived from the suffix common in the names of many opiates.

The endorphins consist of three subfamilies, each derived from a separate precursor molecule. Each precursor molecule, called a "pre-propeptide," is coded for by a separate gene and thus a separate molecule of mRNA. Each of these precursors is made up of a chain of amino acids that can be selectively cleaved and spliced by specific enzymes to synthesize any number of several related neuropeptides. Proenkephalin (PENK), one of the three endogenous opioid precursors, consists of 267 amino acids and is cleaved at several loci to produce Leu-enkephalin, Met-enkephalin, Peptides E, F, and B, in addition to several other peptides. The most abundant of the three families of endorphins, these neuropeptides are found in many different areas of both the central and peripheral nervous systems. They are most concentrated, however, in the medium spiny neurons of the striatum, the ventromedial nucleus of the hypothalamus, and the granule cells of the dentate gyrus, within the hippocampus.

Prodynorphin (PDYN), another one of the three endogenous opioid precursors, is a chain of 254 amino acids and can be cleaved to produce Leu-enkephalin, and several Leu-enkephalin-containing peptides, including dynorphinA, dynorphin B, and alpha- and beta-neoendorphin. For the most part, the distribution of these neuropeptides closely parallels that of the neuropeptides derived from PENK. Levels of PDYN mRNA are, however, particularly concentrated in the magnocellular cells of the hypothalamus and in the granule cell layer of the dentate gyrus, within the hippocampal formation.

Proopiomelanocortin (POMC) is made up of 267 amino acids which can be cleaved to produce beta-lipoprotein and beta-endorphin, in addition to several non-opioid neuropeptides, including ACTH, alpha-MSH, beta-MSH, and gamma-MSH. POMC neuropeptides are found in the basal ganglia, cortex, amygdala, anterior and intermediate lobes of the pituitary, the arcuate nucleus of the hypothalamus, and the nucleus tractus solitarius in the medulla.