Where are endorphins produced

Endorphins: The brain’s natural pain reliever

Endorphins can also release stress and create a feeling of well-being.

Endorphins are the body’s natural painkillers. Endorphins are released by the hypothalamus and pituitary gland in response to pain or stress, this group of peptide hormones both relieves pain and creates a general feeling of well-being.

The name of these hormones comes from the term "endogenous morphine." "Endogenous" because they’re produced in our bodies. Morphine refers to the opioid painkiller whose actions they mimic.

About 20 different types of endorphins exist. The best studied of these is beta-endorphin, which is the one associated with the runner’s high. We also release endorphins when we laugh, fall in love, have sex, and even eat a delicious meal.

How to release endorphins

You can increase your body’s endorphin release by engaging in these activities:

  • Exercise. A moderately intense pace, whether you’re walking fast or doing another form of aerobic activity, seems to be best for releasing endorphins.
  • Acupuncture. An effective way to release endorphin is with pressure points. Placing fine needles into the skin at specific points around the body triggers the release of endorphins.
  • Meditation. Breathing deeply and focusing your brain calms your mind and eases pain.
  • Sex. These hormones are the reason for that blissful feeling many of us get after having sex. Experts believe that endorphins promote the release of other hormones that are involved in feelings of love.
  • Playing music. When you sing, dance, or bang on a drum, you do more than entertain others. You also release a rush of endorphins, which research suggests might increase tolerance to pain.
  • Laughter. A good belly laugh can do wonders for your state of mind. Along with releasing endorphins, laughter alters levels of serotonin and dopamine.
  • Ultraviolet light. It’s no wonder that some people feel happy when they spend time outdoors in the sun. Ultraviolet light stimulates the release of beta-endorphins in the skin.

Endorphins is just one of the four feel-good hormones. To learn more about the others and how they work, head to the beginning of this series. 

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Understanding Endorphins and Their Importance in Pain Management

Hawaii Med J. 2010 Mar; 69(3): 70–71.

Adam S Sprouse-Blum, BA, Greg Smith, BS, Daniel Sugai, BA, and F Don Parsa, MD, FACS

Author information Copyright and License information Disclaimer

The purpose of this article is to briefly review our current understanding of endorphins, specifically beta-endorphins, and how they relate to the field of surgery. Beta-endorphins are neuropeptides involved in pain management, possessing morphine like effects, and are involved in natural reward circuits such as feeding, drinking, sex and maternal behavior.1 Their application to the field of surgery centers on their role in pain management.

Beta-endorphins are primarily synthesized and stored in the anterior pituitary gland2 from their precursor protein proopiomelanocortin (POMC). However, recent studies suggest cells of the immune system are also capable of beta-endorphin synthesis because immune cells possess mRNA transcripts for POMC3 and T-lymphocytes, B-lymphocytes, monocytes and macrophages have been shown to contain endorphins during inflammation. 46

POMC is a large protein that is cleaved into smaller proteins such as beta-endorphin, alpha-melanocyte stimulating hormone (MSH), adrenocorticotropin (ACTH), and others. The pituitary gland synthesizes POMC in response to a signal from the hypothalamus; that signal being corticotroponin-releasing hormone (CRH). The hypothalamus releases CRH in response to physiologic stressors such as pain, as in the postoperative period. When the protein products of POMC cleavage accumulate in excess, they turn hypothalamic CRH production off - that is, feedback inhibition occurs.7

In the peripheral nervous system (PNS), beta-endorphins produce analgesia by binding to opioid receptors (particularly of the mu subtype) at both pre- and post- synaptic nerve terminals, primarily exerting their effect through presynaptic binding. When bound, a cascade of interactions results in inhibition of the release of tachykinins, particularly substance P, a key protein involved in the transmission of pain. 4,8,9 In the PNS, mu-opioid receptors are present throughout peripheral nerves and have been identified in the central terminals of primary afferent neurons, peripheral sensory nerve fibers and dorsal root ganglia. 4

In the central nervous system, beta-endorphins similarly bind mu-opioid receptors and exert their primary action at presynaptic nerve terminals. However, instead of inhibiting substance P, they exert their analgesic effect by inhibiting the release of GABA, an inhibitory neurotransmitter, resulting in excess production of dopamine.8,9 Dopamine is associated with pleasure. In the CNS, mu-opioid receptors are most abundant in descending pain control circuits including the amygdala, mesencephalic reticular formation, periaqueductal gray matter (PAG) and rostral ventral medulla.8

Opioid medications (e.g. Vicodin, Morphine, Fentanyl) are commonly prescribed in the postoperative period. These medications exert their effect by mimicking natural endorphins, binding to mu-opioid receptors in both the CNS and PNS with variable specificity. This is accomplished by sharing a beta-phenylethylamine group, the moiety that binds the opioid receptor.10

Acute administration of exogenous opioids inhibits the production of endogenous opiates (e.g. beta-endorphins). Patients undergoing general anesthesia have shown a significant increase in beta-endorphins during surgery. This increase was effectively inhibited by the co-administration of fentanyl.11,12 In similar studies, Hargreaves et al. showed that patients who underwent dental surgery and were given local anesthetic (lidocaine) alone had increased plasma beta-endorphin levels during and after surgery. However, when fentanyl was co administered, plasma beta-endorphin levels were significantly reduced. Of note, patients reported less pain during the surgery when the fentanyl was co-administered. 13,14

Chronic administration of exogenous opioids inhibits the production of both endogenous opiates and mu-opioid receptors. Multiple studies have demonstrated the down regulation of POMC gene expression and subsequent decrease in endorphin production in rats given chronic morphine.1517 And Zhang et al. found that mu-opioid receptors on beta-endorphin containing neurons of the hypothalamus of guinea pigs decreased in density after chronic-morphine treatment.18 Furthermore, Christie et al. found that exogenous opioids, such as morphine, cause an uncoupling of mu-opioid receptors from their ligand-gated voltage channel with a decrease in both potency and efficacy of the channel.19

Surgical patients occasionally require treatment for pain over an extended period of time. However, chronic administration of opioid analgesics carries significant risks of opioid induced hyperalgesia (OIH), tolerance and addiction. Reports as early as the 19th century reveal patients who experienced hyperalgesia (increased sensitivity to painful stimuli) and allodynia (pain elicited from a normally nonpainful stimulus) upon the cessation of morphine use.20 While down regulation of both endorphins and mu receptors associated with chronic exogenous opioid use likely play a role in OIH, antiopioid peptides are also likely involved. The anti-opioid peptides described thus far include cholecystokinin (CCK), neuropeptide FF (NPFF) and orphanin FQ/nociceptin. These anti-opioid peptides are thought to exert their action by binding mu receptors thereby decreasing their affinity for endorphins and similar opioids.21 Both the down regulation of endorphins and mu receptors, as well as the production of anti-opioid peptides, are processes that occur over time. As these processes occur, patients require increasing amounts of opioids to induce the same level of analgesia, a process known as tolerance.22 Addiction is described as a brain disease resulting in a loss of control over drug taking or in compulsive drug seeking, despite noxious consequences. 23 While the aforementioned mechanisms associated with OIH and tolerance are likely key contributors to opioid addiction, a discussion of addiction would not be complete without briefly discussing the association between the dopaminergic reward system and opiates. As mentioned previously, opioids in the CNS exert their analgesic effect by increasing dopamine release by disinhibiting GABA's effect on dopaminergic neurons. The dopaminergic neurons most associated with addiction are those of the “reward center” including the ventral tegmental area, nucleus accumbens system, prefrontal cortex and extended amygdala.15 To maintain normal dopamine levels, patients who develop tolerance require increased amounts of exogenous opioids. Conversely, when the patient who is reliant on exogenous opioids to maintain dopamine homeostasis attempts to cease opioid use, they frequently suffer severe withdrawal symptoms and may employ drug-seeking behavior.

The degree of pain experienced by the surgical patient during and after a procedure correlates with plasma beta-endorphin level. A study of pre- and postoperative beta-endorphin levels was conducted for various major surgeries. It was found that both pre- and postoperative plasma beta-endorphin levels correlated positively with postoperative pain severity.24 In a similar study comparing plasma beta-endorphin levels between open- and laparoscopic cholecystectomies, an invasive and minimally invasive procedure respectively, Le Blanc et al. concluded that endorphins are most likely excreted in response to postoperative pain.25 Earlier studies have also found a negative correlation between intra-operative plasma beta-endorphin concentration and postoperative pain severity.13,26

Non-opioid medications affect plasma beta-endorphin levels through unknown mechanisms. In a study of osteoarthritis of the knee, both acetaminophen and rofecoxib (a COX-2 inhibitor) were administered to patients with symptomatic osteoarthritis. Rofecoxib produced significantly better analgesia than acetaminophen, reducing pain intensity by 56% and 29%, respectively. However, plasma beta-endorphin levels were unaffected in the rofecoxib group but declined significantly in the acetaminophen group,27 suggesting either rofecoxib supports beta-endorphin synthesis, durability or both or acetaminophen inhibits it. Additionally, Parsa et al. demonstrated decreased postoperative pain severity and opioid requirements following preoperative administration of celecoxib plus gabapentin.28 In the future, more research may reveal the dynamics between beta-endorphins and other non-opioid medications to provide more effective analgesia without the risks associated with opioid medications.

In review, beta-endorphins are proteins that are primarily synthesized by the pituitary gland in response to physiologic stressors such as pain. They function through various mechanisms in both the central and peripheral nervous system to relieve pain when bound to their mu-opioid receptors. Opioid medications function by mimicking natural endorphins, competing for receptor binding. In the acute setting, exogenous opiates inhibit the production of endogenous opiates while in the chronic setting, exogenous opiates inhibit the production of both endogenous opiates and mu-opioid receptors. Risks associated with chronic opiate use include opioid induced hyperalgesia, tolerance and addiction. In the future, we hope to understand the dynamics between beta-endorphins and non-opioid pain medications to offer patients maximal pain management with minimal associated risk.

The authors have no financial interest in the medications reported in this article.

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Hormones of happiness

Hormones are biologically highly active substances that are formed and released into the internal environment of the body by endocrine glands, or endocrine glands. They regulate the functions of organs remote from their place of excretion.

The term "hormone" in Greek means "stimulating to action", although not all hormones have a stimulating effect.

At the moments when the brain recognizes phenomena favorable for our survival, special neurochemical substances are synthesized and released - “happiness hormones”. Each of which leads a person to certain positive sensations. The brain activates their synthesis when it feels the need to satisfy survival needs, which may be the need for food, security, social support, etc. However, the level of “happy hormones” drops sharply after a short-term release until the next need and a pleasant occasion. That is why our mood changes, we feel the ebb and flow of energy and motivation. nine0003

The main hormones that make our world brighter and more pleasant:

  • Dopamine
  • Serotonin
  • Endorphins
  • Oxytocin

Dopamine is a hormone that is synthesized in the brain, adrenal glands, kidneys and intestines. In the adrenal glands, it is the precursor of adrenaline and noradrenaline, the main stress substances in the body. The release of dopamine leads to an increase in blood pressure, an increase in the frequency and strength of heart contractions, and an increase in blood oxygen saturation. Dopamine increases fluid filtration and blood flow in the kidneys, promotes faster excretion of sodium in the urine. The release of this hormone also occurs in shock situations, when a person experiences severe pain or fear. Dopamine helps to adapt to difficult conditions and does not allow you to die from fear or unbearable pain. nine0003

Dopamine is also referred to as a neurotransmitter - with its help, a nerve impulse is transmitted between two neurons. Dopamine, as a neurotransmitter, plays a primary role in the following processes:

  • Formation of motivation
  • Getting pleasure
  • Curiosity, desire to seek answers to questions and learn something new
  • Cognitive enhancement
  • Formation of affection
  • Unleashing creativity

Dopamine ensures survival by telling the body what exactly to spend energy on. If something worthwhile, in your opinion, is in your field of vision, a certain bonus, a trophy, dopamine is released. It encourages action, makes you do everything possible to achieve the goal. For an athlete, such a trophy can be the finish line on the horizon, seeing it, he feels a surge of strength and motivation. That feeling that dopamine evokes is the pleasure of impending success. Primates experience such sensations when they see a fruit on a tree. For a modern person, the extraction of food has not been an extremely difficult task for a long time, and a basket with berries certainly causes pleasant sensations, but they are rather short-lived. Therefore, the brain “saves” dopamine for such purposes, it does not see the point in expending a large amount of energy to get food. Another thing is professional or social activity. Seeking and receiving rewards from society is a sufficient incentive to release dopamine. However, the lifespan of this hormone is not long, so every time you have to strive for a new reward, look for a new stimulus in order to reactivate the synthesis of dopamine. nine0003

Dopamine is released in large quantities during intimacy, and together with oxytocin, it helps to form feelings of attachment, including mother to child. The influence of dopamine on cognitive functions and the learning process has also been established. The hormone helps to memorize new information more easily and stimulates the desire to search for information, thereby facilitating and speeding up the learning process.

Just like dopamine, serotonin is a hormone and a neurotransmitter. Only about 5% of serotonin is synthesized in the brain, and most of it, about 80-90% - in the intestines. Serotonin regulates intestinal motility and uterine contractions during childbirth. The amino acid tryptophan is essential for the formation of serotonin. This amino acid cannot be synthesized in the body, that is, it is indispensable and enters the body only with food. Tryptophan is rich in dairy products, dates, figs, plums, dark chocolate, soy, and tomatoes. The conversion of tryptophan to serotonin provides vitamin D, so sun exposure also helps us become happier.

The field of activity and effects of serotonin is extremely large. It affects almost every system in the body. Serotonin, as the "hormone of happiness," gives us a sense of self-importance. Yes, yes, it stands out, including when we feel respect for our person from others, in connection with which the body begins to feel comfortable and confident. Also, serotonin helps us regulate anxiety and anxiety, reduce depressive background. When there is enough serotonin, we feel emotionally stable, calm, happy. But this is the result of only about 5% of the serotonin that works in our brain. The rest of serotonin is responsible for the following processes:

  • Regulation of sleep and wakefulness
  • Bowel regulation
  • Blood coagulation
  • Contraction of the uterus and fallopian tubes during childbirth
  • Reduced pain threshold
  • Libido and reproductive control

Endorphins - is a group of endogenous opioid peptides. They are formed mainly in the brain from beta-lipotropin, which is produced by the pituitary gland. In addition to the brain, endorphins can be produced in the adrenal glands, pancreas, intestines, dental pulp, and taste buds. nine0003

"Euphoria" - this is how we call the state that endorphins give us. However, endorphin synthesis is not initiated by good news, but, first of all, by physical pain. Endorphin "masks" the pain for a while to give us the opportunity to survive, to be saved. For example, after a severe injury, such as a broken bone or burn, during combat, in athletes in competition. Endorphin helps us get out of stress without a breakdown, maintain common sense, assess the situation, draw conclusions about what actions are currently necessary to save life. Euphoria is accompanied by feelings of joy and delight. But the pain cannot be “masked” for a long time, since it serves as a signal that says “not everything is in order in the body”, therefore the effect of endorphins is not long-lasting. A person also feels a surge of endorphin when laughing or crying. Have you noticed that lovers often laugh together? And, probably, they fall in love at this moment even more, because joint laughter activates the secretion of endorphins. nine0003

Other functions of endorphins:

  • Stimulation of healing processes
  • Control of the activity of the endocrine glands
  • Normalization of blood pressure.

Oxytocin is a peptide hormone from the nuclei of the hypothalamus, which accumulates in the posterior lobe of the pituitary gland of the brain, and from there it is released into the blood. The hormone of hugs, touches and motherhood - oxytocin is associated with perhaps the most pleasant processes. Oxytocin accompanies the entire cycle of reproductive function. The hormone is released during orgasm, promotes the rapid movement of sperm and stimulates muscle contractions, helping the sperm to reach the egg. Oxytocin is also released during childbirth, it promotes contractions of the uterus and cervix. In the future, oxytocin plays an important role during lactation. The birth of a child causes a significant surge of oxytocin in both mother and child. What is especially revealing is the effect of oxytocin in animals: the hormone makes the newborn instinctively cling to the mother, although the baby is not aware of the danger of losing her. nine0003

Oxytocin is released through touch and trust. More precisely, the release occurs immediately before physical contact, it is believed that the stimulus is the expectation of a pleasant contact, and not the contact itself. The feeling that you can count on someone, trust someone or someone trusts you, as well as a sense of security in group relationships - all this is the result of oxytocin.

Alcohol can inhibit the production of oxytocin, as well as the lack of close contact, hugs and communication. nine0003

Hormones of happiness: what are endorphins and how to produce them? mood and beat stress.

Endorphins are responsible for resistance to stress in our body, they also give an analgesic effect and are involved in the regulation of excitation and inhibition. Sometimes they are also called hormones of joy. “Endorphins are a group of chemical compounds that are naturally produced in our body in the neurons of the brain,” says Leonid Arkadyevich Elkin, a surgeon and integral medicine doctor. - For example, in the first phase of stress, when the issue of life has not yet been resolved, a part of the endorphin system works, which activates the function of thinking. After resolving the issue of “life and death”, there comes a moment of inhibition, and the body goes into saving mode. Therefore, the feeling of fear or pain is dulled after unpleasant events. In the medical world, endorphins are often compared to opioid-class painkillers, only endorphins are safe.” nine0003

Why are endorphins so important? "They improve healing processes, accelerate regeneration, promote the formation of thinking - stimulate the formation of associations, fantasies," adds Elkin. Endorphins fight depression, reduce stress and anxiety, boost self-esteem, and aid weight loss. Thanks to endorphins, it is possible to reduce the feeling of pain during childbirth. It is endorphins that make us feel at our best after sex, a good workout or a delicious dinner, and when they are lacking, we want to lie on the couch and look at the ceiling. Impulsive behavior, chronic headaches, anxiety, addictions, and trouble sleeping are some of the few signs of a lack of endorphins. nine0003

“As a neurotransmitter, dopamine is responsible for the formation of motivation, feelings of pleasure, feelings of life and emotional reactions. The release of dopamine is facilitated by the achievement of goals, the feeling of love, tactile sensations, favorite food, rest, physical activity, explains Elkin. Dopamine does not always stimulate the production of positive emotions. First of all, it helps the body adapt in stressful situations - for example, dopamine is released during injuries and pain syndrome. The production of dopamine is inhibited by the intake of alcohol, narcotic drugs, the use of a large amount of fatty and sweet foods. So keep an eye on your diet and give preference to healthy food. There is one important nuance: some drugs that are used in cardiology and psychiatry are involved in the exchange of dopamine, so you should be careful about taking medications. nine0003

Serotonin improves memory, speeds up movement, lowers the pain threshold, ensures proper sleep, participates in reproductive function and controls libido, regulates the functioning of the pelvic organs in women. “The release of serotonin is facilitated by the amino acid tryptophan, glucose and magnesium. Sunlight is also important for the release of serotonin, and therefore vitamin D, which regulates the conversion of tryptophan to serotonin. Caffeine inhibits the production of serotonin, because it worsens appetite, and alcohol, ”says Elkin. A “soothing” glass of wine in the evening may, on the contrary, not relieve tension, but reduce the amount of “happiness hormones” in the blood. Let him be replaced by tea with chamomile or a cup of decaf with bergamot.

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