Endogenous opioids

“Endogenous” means produced within the body, and “opioid” is a word derived from opium. Once scientists discovered that morphine, obtained from poppies, reduces pain by attaching to certain locks (receptors) in the body, they wondered, “If the body has these locks, might it also have matching keys?” The discovery of enkephalins in pig brains in the mid-1970s confirmed that these keys really existed. Other substances were subsequently discovered, including endorphins (a name shortened from “endogenous morphine”) and dynorphins.

The body's opioids are produced as peptides, which are fragments of proteins, and bind to three main types of receptors: mu, delta, and kappa. Each substance has a slightly different preference for these receptors.

Because “endorphins” is such a familiar name, it is easy to use it for all the body's pain-relieving substances. In fact, they consist of several distinct families of substances.

Pain signals travel from peripheral nerves through the spinal cord to the brain. Endogenous opioids reduce the strength of these signals at several points along this pathway.

• Spinal cord — They reduce signal transmission at the first gateway through which pain signals pass on their way to the brain.
• Brain — They regulate how strongly pain is felt and the emotional response to it. They are also involved in the process by which the brain sends a “reduce the signals” message down to the spinal cord through the descending pain modulation pathway.
• Periphery — Opioid receptors also act around injured tissues.

Pain is not determined by nerve signals alone; it is an experience shaped by attention, mood, expectations, and circumstances together. This is why the same stimulus can hurt less on some days and more on others. Endogenous opioids are one of several mechanisms that help with this modulation.

• Feeling refreshed after running or exercise — The uplift in mood after a long run is known as “runner's high” and has been studied in relation to endogenous opioids. You can read about reduced pain sensitivity after exercise in Exercise-induced hypoalgesia.
• Feeling relaxed after massage or acupuncture — The relationship between the relaxation felt during massage and acupuncture and the body's pain-relieving systems is also a topic of research.
• Expectation and reassurance — Experiments have confirmed that endogenous opioids are released in the brain when the expectation of relief reduces pain. Researchers also study the opposite phenomenon, the nocebo effect, in which anxiety and worry increase pain.

Although you cannot directly access the body's pain-relieving systems, everyday habits can help you make good use of them.

• Move regularly. Activities that leave you comfortably out of breath, such as walking, light running, or cycling, are enough. Avoid overdoing it at the start, and try increasing your exercise volume gradually.
• Get enough sleep. Lack of sleep tends to make you more sensitive to pain.
• Make time to unwind. Time spent helping your body feel at ease, through slow breathing, a warm shower, or your favorite music, can help with pain modulation.
• Spend time with others. Relaxed conversation and laughter help both your mind and body unwind.

Naloxone is a drug that attaches to opioid receptors and blocks opioid effects (an antagonist). Its original use is to reverse the effects of opioids in cases of overdose.

In pain research, this drug is also frequently used as an “experimental tool.” If a pain-relieving response disappears when naloxone is administered, this provides a clue that the body's opioid system was involved in that response. The best-known use of this method is in research on pain reduction through expectation. In an experiment published in 1999 by Amanzio and Benedetti, pain relief produced by expectation disappeared when naloxone was administered. The study showed that expecting to feel better can lead to a response in which the brain actually releases the body's own pain-relieving substances. Meanwhile, pain relief produced through learning from repeated experiences (conditioning) sometimes involved different pathways depending on the drug used, also showing that pain modulation involves several pathways beyond opioids.