Name=proopiomelanocortin (adrenocorticotropin/ beta-lipotropin/ alpha-melanocyte stimulating hormone/ beta-melanocyte stimulating hormone/ beta-endorphin)

otheruses redirect|"Runner's high"|the album by the Japanese band The Pillows|Runners High

Endorphins are endogenous opioid polypeptide compounds. They are produced by the pituitary gland and the hypothalamus in vertebrates during strenuous exercise [http://www.nytimes.com/2008/03/27/health/nutrition/27best.html?ei=5087&em=&en=94a1816b72ae11fb&ex=1206763200&adxnnl=1&adxnnlx=1206641040-ZO2PvU1EJBIrKDDUHDVBFw] , [http://www.sportsmedicine.upmc.com/MySportRunningHigh.htm] , excitement, and orgasm [http://news.bbc.co.uk/2/hi/4703166.stm] ; and they resemble the opiates in their abilities to produce analgesia and a sense of well-being. Endorphins work as "natural fever relievers", whose effects may be enhanced by other medications.

The term "endorphin" implies a pharmacological activity (analogous to the activity of the corticosteroid category of biochemicals) as opposed to a specific chemical formulation. It consists of two parts: "endo-" and "-orphin"; these are short forms of the words "endogenous" and "morphine," intended to mean "a morphine like substance originating from within the body." [Goldstein, A. &. Lowery, P.J. "Effect of the opiate antagonist naloxone on body temperature in rats." "Life Science." 1975 Sep 15;17(6):927-31. PMID 1195988]

The term endorphin rush has been adopted in popular speech to refer to feelings of exhilaration brought on by pain, danger, or other forms of stress, [ [http://www.sportsmedicine.upmc.com/MySportRunningHigh.htm#Endorphin The Reality of the "Runner's High", Running, UPMC Sports Medicine, UPMC | University of Pittsburgh Medical Center, Pittsburgh, PA USA ] ] supposedly due to the influence of endorphins. However, this term does not occur in the medical literature.


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 _el. εγκέφαλος, " _la. cerebrum"). [ [http://www.pbs.org/wgbh/aso/databank/entries/dh75en.html A Science Odyssey: People and Discoveries: Role of endorphins discovered ] ] [cite journal |author=Hughes J, Smith T, Kosterlitz H, Fothergill L, Morgan B, Morris H |title=Identification of two related pentapeptides from the brain with potent opiate agonist activity |journal=Nature |volume=258 |issue=5536 |pages=577–80 |year=1975 |pmid=1207728 | doi = 10.1038/258577a0]

* Around the same time in the calf brain, Rabi Simantov and Solomon H. Snyder of the United States found [cite journal |author=Simantov R, Snyder S |title=Morphine-like peptides in mammalian brain: isolation, structure elucidation, and interactions with the opiate receptor |journal=Proc Natl Acad Sci U S A |volume=73 |issue=7 |pages=2515–9 |year=1976 |pmid=1065904 | doi = 10.1073/pnas.73.7.2515] what Eric Simon (who independently discovered opioid receptors in the brain) later termed "endorphin" by an abbreviation of "endogenous morphine", which literally means "morphine produced naturally in the body". Importantly, recent studies have demonstrated that diverse animal and human tissues are in fact capable of producing morphine itself, which is not a peptide. [Poeaknapo C, Schmidt J, Brandsch M, Drager B, Zenk MH. "Endogenous formation of morphine in human cells." "Proceedings of the National Academy of Sciences USA". 2004 Sep 28;101(39):14091-6. PMID 15383669] [Kream RM, Stefano GB. "De novo biosynthesis of morphine in animal cells: an evidence-based model." Med Sci Monit. 2006 Oct;12(10):RA207-19. Review. PMID 17006413]

Mechanism of action

Beta-endorphin is released into the blood (from the pituitary gland) and into the spinal cord and brain from hypothalamic neurons. The beta-endorphin that is released into the blood cannot enter the brain in large quantities because of the blood-brain barrier. The physiological importance of the beta-endorphin that can be measured in the blood is far from clear: beta-endorphin is a cleavage product of pro-opiomelanocortin (POMC) which is also the precursor hormone for adrenocorticotrophic hormone (ACTH). The behavioural effects of beta-endorphin are exerted by its actions in the brain and spinal cord, and probably the hypothalamic neurons are the major source of beta-endorphin at these sites. In situations where the level of ACTH is increased (e.g. Addison disease), the level of endorphins also increases slightly.

Beta-endorphin has the highest affinity for the μ1-opioid receptor, slightly lower affinity for the μ2- and δ-opioid receptors and low affinity for the κ1-opioid receptors. μ-receptors are the main receptor through which morphine acts. Classically, μ-receptors are presynaptic, 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, and receptors are often found at postsynaptic locations as well as presynaptically.


Scientists debate whether specific activities release measurable levels of endorphins. Much of the current data comes from animal models which may not be relevant to humans. The studies that do involve humans often measure endorphin plasma levels, which do not necessarily correlate with levels in the CNS. Other studies use a blanket opioid antagonist (usually naloxone) to indirectly measure the release of endorphins by observing the changes that occur when any endorphin activity that might be present is blocked.

Capsaicin (the active chemical in red chili peppers) also has been shown to stimulate endorphin release. [ [http://www.chronogram.com/issue/2005/11/wholeliving/index.php Chronogram - Endorphins - Nov 2005 ] ] Topical capsaicin has been used as a treatment for certain types of chronic pain.

Runner's high

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 breathing is difficult. This also corresponds with the time that muscles use up their stored glycogen. Workouts that are most likely to produce endorphins include running, swimming, cross-country skiing, long distance rowing, bicycling, weight lifting, aerobics, or playing a sport such as basketball, rugby, lacrosse, or American 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. [cite journal |author=Hinton E, Taylor S |title=Does placebo response mediate runner's high? |journal=Percept Mot Skills |volume=62 |issue=3 |pages=789–90 |year=1986 |pmid=3725516] Studies in the early 1980s cast doubt on the relationship between endorphins and the runner's high for several reasons:
* The first was that when an antagonist (pharmacological agent that blocks the action for the substance under study) was infused (e.g. naloxone) or ingested (naltrexone) the same changes in mood state occurred when the person exercised with no blocker.

A [http://www.cnn.com/2004/HEALTH/01/11/marijuana.exercise.reut study in 2004] by Georgia Tech found that runner's high might be caused by the release of another naturally produced chemical, the endocannabinoid anandamide. Anandamide is similar to the active chemical, THC, found in marijuana. The authors suggest that the body produces this chemical to deal with prolonged stress and pain from strenuous exercise, similar to the original theory involving endorphins. However, the release of anandamide was not reported with the cognitive effects of the runner’s high; this suggests that anandamide release may not be significantly related to runner's high. [Sparling PB, Giuffrida A, Piomelli D, Rosskopf L, Dietrich A. "Exercise activates the endocannabinoid system."Neuroreport". 2003 Dec 2;14(17):2209-11. PMID 14625449]

In 2008, researchers in Germany reported that the myth of the runner's high was in fact true. Using PET scans combined with recently available chemicals that reveal endorphins in the brain, they were able to compare runners’ brains before and after a run. The runners the researchers recruited were told that the opioid receptors in their brains were being studied, and did not realize that their endorphin levels were being studied in regard to the runner's high.

The participants were scanned and received psychological tests before and after a two-hour run. Data received from the study showed endorphins were produced during the exercise and were attaching themselves to areas of the brain associated with emotions (limbic and prefrontal areas). [http://www.nytimes.com/2008/03/27/health/nutrition/27best.html?ei=5087&em=&en=94a1816b72ae11fb&ex=1206763200&adxnnl=1&adxnnlx=1206641040-ZO2PvU1EJBIrKDDUHDVBFw]


In 1999, clinical researchers reported that inserting acupuncture needles into specific body points triggers the production of endorphins. [ [http://www.abc.net.au/science/news/stories/s27924.htm News in Science - Acupuncture works on endorphins - 04/06/1999 ] ] In another study, higher levels of endorphins were found in cerebrospinal fluid after patients underwent acupuncture. [cite journal |author=Clement-Jones V, McLoughlin L, Tomlin S, Besser G, Rees L, Wen H |title=Increased beta-endorphin but not met-enkephalin levels in human cerebrospinal fluid after acupuncture for recurrent pain |journal=Lancet |volume=2 |issue=8201 |pages=946–9 |year=1980 |pmid=6107591 |doi=10.1016/S0140-6736(80)92106-6] In addition, naloxone appeared to block acupuncture’s pain-relieving effects. However, skeptics say that not all studies point to that conclusion, [cite journal |author=Kenyon J, Knight C, Wells C |title=Randomised double-blind trial on the immediate effects of naloxone on classical Chinese acupuncture therapy for chronic pain |journal=Acupunct Electrother Res |volume=8 |issue=1 |pages=17–24 |year=1983 |pmid=6135300] and that in a trial of chronic pain patients, endorphins did not produce long-lasting relief. Endorphins may be released during low levels of pain and physical stimulation when it lasts over 30 minutes. Questions remain as to whether the prolonged low level of pain stimulation as in Capsaicin, acupuncture and running or physical activity alone are the threshold that activates endorphin release.


External links

* [http://www.news-medical.net/?id=33701# A genetic influence on alcohol addiction found - lack of endorphin]

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