Endorphin

For other uses, see Endorphin (disambiguation).

Endorphins are endogenous opioid biochemical compounds. They are peptides produced by the pituitary gland and the hypothalamus in vertebrates, and they resemble the opiates in their abilities to produce analgesia and a sense of well-being. In other words, they work as "natural pain killers."

The term "endorphin" is used generally to refer to all of the endogenous opioid compounds and implies a pharmacological activity (analogous to the activity of the corticosteroid category of biochemicals) as opposed to a specific chemical formulation.

History

These opioid neuropeptides were first discovered in 1975 by two independent groups of investigators. John Hughes and Hans Kosterlitz of Scotland isolated --- from the brain of a pig --- what they called "enkephalins" (from the Greek εγκέφαλος, "cerebrum"). Around the same time in the calf brain, Rabi Simantov and Solomon H. Snyder of the United States found what they later termed "endorphin" *, an abbreviation of "endogenous morphine", which means morphine produced naturally in the body.

Molecular biology

The best-known endorphins are α-, β- and γ-endorphin, of which β-endorphin appears to be most implicated in pain relief.

The amino acid residue sequence (primary structure) of β-endorphin is: Tyr-Gly-Gly-Phe-Met-Thr-Ser-Glu-Lys-Ser-Gln-Thr-Pro-Leu-Val-Thr-Leu-Phe-Lys-Asn-Ala-Ile-Ile-Lys-Asn-Ala-Tyr-Lys-Lys-Gly-GluOH (Fries, 2002).

Mechanism of action

Beta-endorphin is released in peripheral, spinal and supra-spinal locations (i.e. body, spine and brain). Beta-endorphin has the highest affinity for the Mu1-opioid receptor, slightly lower affinity for the Mu2 and Delta-opioid receptors and low affinity for the Kappa1-opioid receptors. Classically, Mu receptors are presynapic, and inhibit neurotransmitter release, through this mechanism, they inhibit the release of the inhibitory neurotransmitter GABA, and disinhibit the dopamine pathways, causing more dopamine to be released. By hijacking this process, exogenous opioids cause inappropriate dopamine release, and lead to aberrant synaptic plasticity which causes addiction. Opioid receptors have many other and more important roles in the brain and periphery however, modulating pain, cardiac, gastric and vascular function as well as possibly panic and satiation.

Activity

Endorphins regulate feelings of pain and hunger and are connected to the production of sex hormones.

Oddly enough, they are also generated in response to certain spices such as chili peppers. The spicier the chili pepper, (habaneros are the hottest) the more endorphins are released. Chili peppers have thus been used as a treatment for certain types of chronic pain.

According to some reports, laughter also releases endorphins in the brain. So besides widening the blood vessels, suppressing the production of stress hormones and raising antibody levels in the blood, laughing would thus also have an analgesic effect.

The placebo effect has been linked to endorphins. When a placebo is given, the belief that it is medicine that will help and the expectation that it will help release endorphins that do help the pain. In a scientific study, a volunteer received pain by a compression cuff on his arm. In the first trial, no drug was administered and the patient showed signs of pain including facial grimace, increased blood pressure, and sweating. During the next trial, the physican informed the volunteer that he would be injected with morphine and that he would feel no pain. The morphine was injected, the pain compression repeated, and this time the volunteer showed and reported no pain. The morphine and compression was repeated several times. Then, the volunteer was unknowingly injected with a saline placebo, but still reported no sign of pain, though the last time he was unmedicated the signs of pain were obvious. In a last test, the patients’ ‘morphine’ was actually an injection of naloxene, a chemical that blocks the effects of endorphins. Even though the volunteer believed the shot was morphine and expected relief, the endorphins’ effect was blocked by the naloxene injection and the volunteer displayed the same signs of pain as the first unmediacated trial. (Groopman 169)

Another widely publicized effect of endorphin production is the so-called "runner's high", which is said to occur when strenuous exercise takes a person over a threshold that activates endorphin production. Endorphins are released during long, continuous workouts, when the level of intensity is between moderate and high and if is difficult to breathe. This also corresponds with the time that muscles use up their stored energy and begin functioning without oxygen. Workouts that are most likely to produce endorphins include running, swimming, cross-country skiing, bicycling, aerobics, or playing a sport such as basketball, soccer, or even football. However, some scientists question the mechanisms at work, their research possibly demonstrating the high comes from completing a challenge rather than as a result of exertion.

Research has also shown that video game playing can release endorphins.

Ultraviolet light may also stimulate the release of endorphins. Some scientists speculate that this is the reason people continue to tan despite the possibility of skin cancer.

Meditation has also been shown to release endorphins. In a research study, it was found that mediatators experienced the same spike in levels of beta-endorphin in the blood stream that elite runners did.

In 1999, clinical researchers reported that inserting the acupuncture needles into specific body points triggers the production of endorphins [1].

References

• Groopman, Jerome. The Anatomy of Hope. New York: Random House, 2004. 169-173.
• Simantov, R. & Snyder, H. (1976). Morphine-like peptides in mammalian brain: Isolation, structure elucidation, and interactions with the opiate receptor. Proceedings of the National Academy of Sciences (USA), 73: 2515, 1976.
• Goldberg, Jeff (1988). Anatomy of a Scientific Discovery. Bantam Books, 1988. ISBN 0553346318; ISBN 0553176161 (British edition); ISBN 0553052616 (hardcover).
• Fries, DS (2002). Opioid Analgesics. In Williams DA, Lemke TL. Foye's Principles of Medicinal Chemistry (5 ed.). Philadelphia: Lippincott Williams & Wilkins. ISBN 0-683-30737-1.