Endorphins and Other Neuropeptides

The brain's own opioids, substance P, orexin, neuropeptide Y and more: slower, longer-acting chemical messengers built from short chains of amino acids.

Neuropeptides are chains of a few to a few dozen amino acids. More than a hundred have been found in the nervous system. Unlike classical transmitters, which are made and recycled at the axon terminal, neuropeptides are made in the cell body, packaged in larger "dense-core" vesicles and shipped to the terminals. They are often released only when a neuron fires rapidly, act on G-protein-coupled receptors, can diffuse further, and are broken down rather than recycled.

The body's own opioids

In 1973 Candace Pert and Solomon Snyder (and independently others) found specific opiate receptors in the brain. Why would the brain have receptors for a poppy extract? In 1975 John Hughes and Hans Kosterlitz identified the answer: natural opioid peptides they called enkephalins. Soon after, endorphins ("endogenous morphine") and dynorphins were found. They damp pain signals in the spinal cord and brainstem and contribute to reward, stress responses and probably the "runner's high" (though endocannabinoids may play a bigger role there).

Opioid drugs — morphine, heroin, fentanyl — mimic these peptides at the mu-opioid receptor. Because mu receptors in the brainstem also control breathing, overdose can be fatal. Naloxone blocks them and can reverse an overdose.

A sampler of other neuropeptides

Substance P transmits pain signals and inflammation. Orexin (also called hypocretin), made by a few thousand hypothalamic neurons, stabilises wakefulness; its loss causes narcolepsy. Neuropeptide Y drives appetite and is involved in stress resilience. Oxytocin and vasopressin influence social bonding and are also hormones. CGRP is involved in migraine, and drugs blocking it are now migraine treatments. Corticotropin-releasing hormone (CRH) kicks off the stress response.