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Endorphin
.
Endorphins
are endogenous opioid  polypeptidecompounds. They are produced by the  pituitary gland and thehypothalamusinvertebratesduring strenuous exercise,[1] excitement, pain,andorgasm,[2]HYPERLINK \l "cite_note- urlGet_more_than_zeds_in_bed_-_Mind_.26_body_magazine_-_NHS_Direct-2"[3]andthey resemble theopiatesin their abilities to produceanalgesiaand a sense of well-being. Endorphins work as "natural fever relievers", whose effects may be enhanced by other medications.The term "endorphin" implies a pharmacologicalactivity (analogous to the activity of thecorticosteroidcategory of biochemicals) as opposed to a specific chemical formulation. Itconsists 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 arereleased which prevent nerve cells from releasing more pain signals. Endorphins allowsomeone to immediately after injury feel a sense of power and control over themselveswhich allows them to persist with activity for an extended time.
History
Opioid neuropeptideswere first discovered in 1975 by two independent groups of investigators.
•
John Hughes andHans Kosterlitzof Scotlandisolated — from the brainof a pig  — what they calledenkephalins(from theGreek  εγκέφαλος,
cerebrum
).[5]HYPERLINK \l "cite_note-5"[6] 
•
Around the same time in thecalf   brain, Rabi Simantov andSolomon H. Snyder of  theUnited Statesfound[7]what Eric Simon (who independently discovered opioid receptors in the brain) later termed "endorphin" by anabbreviationof "endogenous morphine", which literally means "morphine  produced naturally in the body".[
citation needed 
] Importantly, recent studies have demonstrated thatdiverse animal and human tissues are in fact capable of producing morphine itself,which is not a peptide.[8]HYPERLINK \l "cite_note-pmid17006413-8"[9] 
 
Mechanism of action
Beta-endorphinis released into the blood (from the pituitary gland) and into the spinalcord 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 spinalcord, and probably the hypothalamic neurons are the major source of beta-endorphin atthese sites. In situations where the level of ACTH is increased (e.g. Addison disease
 
), thelevel of endorphins also increases slightly.Beta-endorphin has the highest affinity for the μ1-opioid receptor , slightly lower affinityfor the μ2- and δ-opioid receptorsand low affinity for the κ1-opioid receptors. μ- receptors are the main receptor through whichmorphine acts. Classically, μ-receptors are  presynaptic, and inhibit neurotransmitter release; through this mechanism, they inhibit therelease of the inhibitory neurotransmitter  GABA, and disinhibit thedopamine  pathways, causing more dopamine to be released. By hijacking this process, exogenous opioidscause inappropriate dopamine release, and lead to aberrantsynaptic plasticity, whichcauses addiction. Opioid receptors have many other and more important roles in the brainand periphery however, modulating pain, cardiac, gastric and vascular function as well as possibly panic and satiation, and receptors are often found at postsynaptic locations aswell as presynaptically.
Activity
Scientists debate whether specific activities release measurable levels of endorphins.Much of the current data comes from animal models which may not be relevant tohumans. The studies that do involve humans often measure endorphin plasmalevels,which do not necessarily correlate with levels in theCNS. Other studies use a blanketopioid 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 stimulateendorphin 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'shigh
", which is said to occur when strenuous exercise takes a person over a threshold thatactivates endorphin production. Endorphins are released during long, continuousworkouts, when the level of intensity is between moderate and high, and breathing isdifficult. This also corresponds with the time that muscles use up their stored glycogen. Workouts that are most likely to produce endorphins include, boxing, running, swimming,cross-country skiing,long distancerowing,cycling, hockey,tennis, weight lifting, aerobics, or playing a sport such assoccer ,  basketball,rugby,lacrosse, Paintball or American football.However, some scientists question the mechanisms at work, their research possiblydemonstrating the high comes from completing a challenge rather than as a result of exertion.[11] 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 theaction for the substance under study) was infused (e.g.naloxone) or ingested(naltrexone
 
) the same changes in mood state occurred as when the personexercised with no blocker.A study in 2003 by Georgia Tech found that runner's high might be caused by the releaseof another naturally produced chemical, Anandamide. Anandamide is similar to the activeendocannabinoidanandamide,[12]HYPERLINK \l "cite_note-pmid14625449- 12"[13]The authors suggest that the body produces this chemical to deal with prolongedstress and pain from strenuous exercise, similar to the original theory involvingendorphins. However, the release of anandamide was not reported with the cognitiveeffects of the runner’s high; this suggests that anandamide release may not besignificantly related to runner's high.[13]In 2008, researchers in Germany reported that the myth of the runner's high was not amyth but was in fact true. Using PET scans combined with recently available chemicalsthat reveal endorphins in the brain, they were able to compare runners’ brains before andafter a run.[14] 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 theexercise and were attaching themselves to areas of the brain associated with emotions(limbic and prefrontal areas).[15]An investigated possiblity is that a molecule, such as anandamidecarries endorphins through the blood-brain barrier , as endorphins are too large to cross the BBB bythemselves. If not, endorphins may be produced in the brain itself.
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