Endorphin

"Runner's high" redirects here. For the album by the Japanese band The Pillows, see Runners High.

For other uses, see Endorphin (disambiguation).

Endorphins ("endogenous morphine") are endogenous opioid peptides that function as neurotransmitters. They are produced by the pituitary gland and the hypothalamus in vertebrates during exercise, excitement, pain, consumption of spicy food, love and orgasm, and they resemble the opiates in their abilities to produce analgesia and a feeling of well-being.

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."

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, 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.

History

Opioid neuropeptides were first discovered in 1974 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 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.

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; though 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.

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 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. 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 his or her body's physical limit. This means that runners can keep running despite pain, continuously surpassing what they once considered to be their limit.

In 2008, researchers in Germany reported on the mechanisms that cause the runner's high. 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).

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 runner's high questioned the mechanisms at work, their data possibly demonstrated that the "high" comes from completing a challenge rather than as a result of exertion. 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. 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.

Relaxation

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

Acupuncture

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

Pregnancy

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 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.

Etymology

From French endorphine, from (endo)gène ‘endogenous’ + mo(rphine) ‘morphine’.

External links

• Endorphins at the US National Library of Medicine Medical Subject Headings (MeSH)
• "A genetic influence on alcohol addiction found - lack of endorphin". News-Medical.Net. Dec-2007-12-21. Retrieved 2008-10-15.