Endorphin: Wikis


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proopiomelanocortin (adrenocorticotropin/ beta-lipotropin/ alpha-melanocyte stimulating hormone/ beta-melanocyte stimulating hormone/ beta-endorphin)
Symbol POMC
Entrez 5443
HUGO 9201
OMIM 176830
RefSeq NM_000939
UniProt P01189
Other data
Locus Chr. 2 p23

Endorphins are endogenous opioid polypeptide compounds. They are produced by the pituitary gland and the hypothalamus in vertebrates during exercise,[1] excitement, pain, consumption of spicy food and orgasm,[2][3] and they resemble the opiates in their abilities to produce analgesia and a feeling of well-being. Endorphins work as "natural pain relievers."

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."[4]

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,[1] supposedly due to the influence of endorphins. When a nerve impulse reaches the spinal cord, endorphins are released which prevent nerve cells from releasing more pain signals. Immediately after injury, endorphins allow animals to feel a sense of power and control over themselves that allows them to persist with activity for an extended time.



Opioid neuropeptides were first discovered in 1975 by two independent groups of investigators.

  • Around the same time in the calf brain, Rabi Simantov and Solomon H. Snyder of the United States found[7] 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".[4] Importantly, recent studies have demonstrated that diverse animal and human tissues are in fact capable of producing morphine itself, which is not a peptide.[8][9]

Mechanism of action

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

β-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 opioid receptors are the main receptor through which morphine acts. Classically, μ opioid 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 central nervous system. 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.[10] 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. During a release of endorphins the person may be exposed to bodily harm from strenuous bodily functions after going past their body's physical limit. Fortunately, studies indicate that the body has no physical limit in the case of long distance running. This means that runners can keep running despite pain, continuously surpassing what they once considered to be their limit. They may be able to keep running despite pain, and thus possibly come to bodily harm from endorphin release. Workouts that are most likely to produce endorphins to the extent of damage at the body's physical limit include sports and other strenuous exercises.

In 2008, researchers in Germany reported that the myth of the runner's high was not a myth but 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.[11] 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).[12]

It is also suggested by many that endorphins are some of the many chemicals that contribute to runner's high; other candidates include epinephrine, serotonin, dopamine and more.

Previous research on the role of endorphins in producing runners high questioned the mechanisms at work, their data possibly demonstrating that the "high" comes from completing a challenge rather than as a result of exertion.[13] 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 as when the person exercised with no blocker.
  • A study in 2003 by Georgia Tech found that runner's high might be caused by the release of another naturally produced chemical, anandamide.[14][15] 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.[15]


In 2003, clinical researchers reported that profound relaxation in a float tank triggers the production of endorphins.[16] This explains the pain relief experienced during float sessions.[17]


In 1999, clinical researchers reported that inserting acupuncture needles into specific body points triggers the production of endorphins.[18][19] In another study, higher levels of endorphins were found in cerebrospinal fluid after patients underwent acupuncture.[20] In addition, naloxone appeared to block acupuncture’s pain-relieving effects.

However, skeptics[21] say that not all studies point to that conclusion,[22] 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. Proponents of acupuncture have yet to prove that the prolonged low level of pain stimulation from acupuncture, running, or physical activity alone are the threshold that activates endorphin release. Critics of studies showing positive results of acupuncture also point out that certain countries (China and Russia chief among them) show positive results nearly 100% of the time in such studies, a statistical impossibility, calling further into question whether endorphin release is in any way related to the claims of pain relief made by proponents of acupuncture [23]

The foetus excretes beta-endorphins into the maternal blood through the placenta from the 3rd month of pregnancy. Its role is still debated.


A placental tissue of foetal origin — i.e. the syncytiotrophoblast — excretes beta-endorphins into the maternal blood system from the 3rd month of pregnancy. A recent study [24] proposes an adaptive background for this phenomenon. The authors argue that foetuses make their mothers endorphin-dependent then manipulate them to increase nutrient allocation to the placenta. Their hypothesis predicts that: (1) anatomic position of endorphin production should mirror its presumed role in foetal-maternal conflict; (2) endorphin levels should co-vary positively with nutrient carrying capacity of maternal blood system; (3) postpartum psychological symptoms (such as postpartum blues, depression and psychosis) in humans are side-effects of this mechanism that can be interpreted as endorphin-deprivation symptoms; (4) shortly after parturition, placentophagy could play an adaptive role in decreasing the negative side-effects of foetal manipulation; (5) later, breast-feeding induced endorphin excretion of the maternal pituitary saves mother from further deprivation symptoms. These predictions appear to be supported by empirical data. [24]


  1. ^ a b "The Reality of the "Runner's High"". UPMC Sports Medicine. University of Pittsburgh Schools of the Health Sciences. http://www.sportsmedicine.upmc.com/MySportRunningHigh.htm. Retrieved 2008-10-15. 
  2. ^ "'Sexercise' yourself into shape". Health. BBC News. 2006-02-11. http://news.bbc.co.uk/2/hi/4703166.stm. Retrieved 2008-10-15. 
  3. ^ "Get more than zeds in bed -". Mind & body magazine - NHS Direct. UK National Health Service. http://www.nhsdirect.nhs.uk/articles/article.aspx?articleId=2504. Retrieved 2008-10-15. 
  4. ^ a b Goldstein A, Lowery PJ (September 1975). "Effect of the opiate antagonist naloxone on body temperature in rats". Life sciences 17 (6): 927–31. doi:10.1016/0024-3205(75)90445-2. PMID 1195988. 
  5. ^ "Role of endorphins discovered". PBS Online: A Science Odyssey: People and Discoveries. Public Broadcasting System. 1998-01-01. http://www.pbs.org/wgbh/aso/databank/entries/dh75en.html. Retrieved 2008-10-15. 
  6. ^ Hughes J, Smith T, Kosterlitz H, Fothergill L, Morgan B, Morris H (1975). "Identification of two related pentapeptides from the brain with potent opiate agonist activity". Nature 258 (5536): 577–80. doi:10.1038/258577a0. PMID 1207728. 
  7. ^ Simantov R, Snyder S (1976). "Morphine-like peptides in mammalian brain: isolation, structure elucidation, and interactions with the opiate receptor". Proc Natl Acad Sci USA 73 (7): 2515–9. doi:10.1073/pnas.73.7.2515. PMID 1065904. 
  8. ^ Poeaknapo C, Schmidt J, Brandsch M, Dräger B, Zenk MH (September 2004). "Endogenous formation of morphine in human cells". Proceedings of the National Academy of Sciences of the United States of America 101 (39): 14091–6. doi:10.1073/pnas.0405430101. PMID 15383669. 
  9. ^ Kream RM, Stefano GB (October 2006). "De novo biosynthesis of morphine in animal cells: an evidence-based model". Medical science monitor : international medical journal of experimental and clinical research 12 (10): RA207–19. PMID 17006413. http://www.medscimonit.com/fulltxt.php?ICID=459203. 
  10. ^ Klosterman L (2005-11-01). "Endorphins". Chronogram. Luminary Publishing, Inc.. http://www.chronogram.com/issue/2005/11/wholeliving/index.php. Retrieved 2008-10-15. 
  11. ^ Boecker H, Sprenger T, Spilker ME, Henriksen G, Koppenhoefer M, Wagner KJ, Valet M, Berthele A, Tolle TR (February 2008). "The Runner's High: Opioidergic Mechanisms in the Human Brain". Cerebral cortex (New York, N.Y. : 1991) 18: 2523. doi:10.1093/cercor/bhn013. PMID 18296435. 
  12. ^ Kolata G (2008-03-27). "Yes, Running Can Make You High". Health. New York Times. http://www.nytimes.com/2008/03/27/health/nutrition/27best.html?ei=5087&em=&en=94a1816b72ae11fb&ex=1206763200&adxnnl=1&adxnnlx=1206641040-ZO2PvU1EJBIrKDDUHDVBFw. Retrieved 2008-10-15. 
  13. ^ Hinton E, Taylor S (1986). "Does placebo response mediate runner's high?". Percept Mot Skills 62 (3): 789–90. PMID 3725516. 
  14. ^ "Study links marijuana buzz to 'runner's high'". CNN.com. 2004-01-11. http://edition.cnn.com/2004/HEALTH/01/11/marijuana.exercise.reut/. Retrieved 2008-10-15. 
  15. ^ a b Sparling PB, Giuffrida A, Piomelli D, Rosskopf L, Dietrich A (December 2003). "Exercise activates the endocannabinoid system". Neuroreport 14 (17): 2209–11. doi:10.1097/01.wnr.0000097048.56589.47. PMID 14625449. 
  16. ^ Anette Kjellgren, 2003, The experience of floatation REST (restricted Environmental stimulation technique), subjective stress and pain, Goteborg University Sweden,
  17. ^ Kjellgren A, Sundequist U, et al. "Effects of flotation-REST on muscle tension pain". Pain Research and Management 6 (4): 181-9
  18. ^ Johnson C (1999-06-04). "Acupuncture works on endorphins". News in Science, ABC Science Online. Australian Broadcasting Corporation. http://www.abc.net.au/science/news/stories/s27924.htm. Retrieved 2008-10-15. 
  19. ^ Napadow V, Ahn A, Longhurst J, Lao L, Stener-Victorin E, Harris R, Langevin HM (September 2008). "The status and future of acupuncture clinical research". Journal of alternative and complementary medicine (New York, N.Y.) 14 (7): 861–9. doi:10.1089/acm.2008.SAR-3. PMID 18803495. 
  20. ^ Clement-Jones V, McLoughlin L, Tomlin S, Besser G, Rees L, Wen H (1980). "Increased beta-endorphin but not met-enkephalin levels in human cerebrospinal fluid after acupuncture for recurrent pain". Lancet 2 (8201): 946–9. doi:10.1016/S0140-6736(80)92106-6. PMID 6107591. 
  21. ^ http://www.sciencebasedmedicine.org/?p=252
  22. ^ Kenyon J, Knight C, Wells C (1983). "Randomised double-blind trial on the immediate effects of naloxone on classical Chinese acupuncture therapy for chronic pain". Acupunct Electrother Res 8 (1): 17–24. PMID 6135300. 
  23. ^ http://www.ncbi.nlm.nih.gov/pubmed/9551280
  24. ^ a b Apari P, Rózsa L (2006). "Deal in the womb: fetal opiates, parent-offspring conflict, and the future of midwifery". Medical Hypotheses 67: 1189-1194. http://www.zoologia.hu/list/apari_rozsa.pdf. 

External links

Simple English

Endorphins are proteins that are similar to opioids. They are made by the endocrine system of many vertebrates. When they are released into the body, they cause a sense of well-being. They also act as analgesics -- that is, they can fight pain.[1] They are sometimes named "natural pain killers". Endorphins were first found in 1970s. In 1977, Roger Guillemin and Andrew W. Schally won the Nobel Prize in medicine because of their studies on hormones in the brain, including endorphins.[2]

The term endorphin is a general name for many opioid-like proteins. (It consists of two parts: endo and orphin; these are short forms of the words endogenous metersorphine which means "a morphin-like substance which is produced by the human body".[3]) Special endorphins have their own names, like enkephalin and β-endorphin.



Four types of endorphins are created in the human body. They are named alpha (α), beta (β), gamma (γ) and sigma (σ) endorphins. The four types have different numbers and types of amino acids in their molecules; they have between 16 and 31 amino acids in each molecule.

Beta-endorphins (β-endorphins) are the most powerful endorphins in the body. They are usually found in the hypothalamus and pituitary gland. More endorphins are released in the pituitary gland during times of pain or stress. Exercise increases the endorphin release too. For the same reason, exercise results in a better mood.

Met-enkephalin and leu-enkephalin are found in the brain stem and spinal cord; they are the pain killers of the spinal cord.[4] Both of them have five amino acids in their structure; the first four are similar, but the last one is different.


All of the endorphins bind to the opioid receptors in the brain. Many of the analgesic (pain killer) drugs have a similar action in the brain. The main difference between the natural endorphins and the analgesic drugs is that natural endorphins are cleared from the blood very quickly. Endorphins are also involved in the release of sex hormones in the pituitary gland.[5] Also, scientists think that acupuncture results in the release of more endorphins.[6] Endorphins may have a role in obesity, diabetes and psychiatric diseases too.[7]

Endorphin rush

The term endorphin rush is sometimes used in normal speech to refer to a feeling of wellness caused by exercise, danger or stress.[8] However, it is not a medical term, and it is not proven that higher endorphin production after exercise really has a role in the wellness feeling.

Another term which is commonly used is runner's high. It refers to the feeling being "high" (full of energy and wellness) after exercise. It is commonly said that the "high" is a result of the release of bigger amounts of endorphins in the body during the exercise. However, some scientists think this feeling is caused by the challenge, and is not related to endorphin release.[9]

For example, in some studies a drug was given to people which blocked the effect of endorphins. These people still felt the runner's high; it means this feeling is not caused by the release of endorphins in the blood. Another study was performed in 2004, which showed this feeling is related to a different body chemical named "anadamide".[10] Anadamide is similar to one of the chemicals which is found in marijuana. The body produces anadamide to fight with the stress and pain in a long exercise.


  1. Hartwig, AC (May-Jun 1991). [Expression error: Unexpected < operator "Peripheral beta-endorphin and pain modulation"]. Anesthesia progress 38 (3): 75-8. PMID 1814247. 
  2. "The Nobel Prize in Physiology or Medicine 1977". http://nobelprize.org/nobel_prizes/medicine/laureates/1977/. Retrieved 2007-10-06. 
  3. "Definition of endorphin". Merram-Webster dictionary. http://mw1.merriam-webster.com/dictionary/endorphin. Retrieved 2007-10-07. 
  4. Guyton, AC; Hall, JE (2001). Textbook of Medical Physiology (10th ed ed.). WB Saunders. pp. 556. 
  5. Bancroft, J (Sep 2005). [Expression error: Unexpected < operator "The endocrinology of sexual arousal."]. The Journal of endocrinology 186 (3): 411-27. PMID 16135662. 
  6. Best, Ben. "Brain Neuron Physiology". http://www.benbest.com/science/anatmind/anatmd1.html. Retrieved 2007-10-07. 
  7. Dalayeun JF, Norès JM, Bergal S (1993). [Expression error: Unexpected < operator "Physiology of beta-endorphins. A close-up view and a review of the literature"]. Biomedicine & pharmacotherapy 47 (8): 311-20. PMID 7520295. 
  8. "Runner's high". University of Pittsburgh Medical Center. http://www.sportsmedicine.upmc.com/MySportRunningHigh.htm#Endorphin. Retrieved 2007-10-18. 
  9. Hinton E, Taylor S (1986). [Expression error: Unexpected < operator "Does placebo response mediate runner's high?"]. Percept Mot Skills 62 (3): 789-90. PMID 3725516. 
  10. "Study links marijuana buzz to 'runner's high'". CNN. 2004-01-11. http://www.cnn.com/2004/HEALTH/01/11/marijuana.exercise.reut. Retrieved 2007-10-18. 

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