Revision as of 21:37, 16 March 2009
Individual differences |
Methods | Statistics | Clinical | Educational | Industrial | Professional items | World psychology |
Biological: Behavioural genetics · Evolutionary psychology · Neuroanatomy · Neurochemistry · Neuroendocrinology · Neuroscience · Psychoneuroimmunology · Physiological Psychology · Psychopharmacology (Index, Outline)
Endorphins are endogenous opioid biochemical compounds. They are peptides produced by the pituitary gland and the hypothalamus in vertebrates, and they resemble the opiates in their abilities to produce analgesia and a sense of well-being. In other words, they might work as "natural pain killers."
These 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 εγκέφαλος, "cerebrum"). Around the same time in the calf brain, Rabi Simantov and Solomon H. Snyder of the United States found what they later termed "endorphin", an abbreviation of "endogenous morphine", which literally means "morphine produced naturally in the body". In fact, morphine itself is not a peptide, and although it is produced by some plants (the opium poppy) it is not produced by animals.
There are at least three different families of opioid peptides. The endorphins are products of a gene that encodes a large precursor peptide called pro-opiomalanocortin (POMC); POMC is expressed in the pituitary gland and in the arcuate nucleus of the hypothalamus. The best-known endorphins are α-, β- and γ-endorphin, of which β-endorphin appears to be most implicated in pain relief.
The amino acid residue sequence (primary structure) of β-endorphin is: Tyr-Gly-Gly-Phe-Met-Thr-Ser-Glu-Lys-Ser-Gln-Thr-Pro-Leu-Val-Thr-Leu-Phe-Lys-Asn-Ala-Ile-Ile-Lys-Asn-Ala-Tyr-Lys-Lys-Gly-GluOH (Fries, 2002).
Other opioid peptides are the enkephalins and the dynorphins. The term enkephalin mainly refers to two peptides, [Met]-enkephalin and [Leu]-enkephalin, which are both products of the proenkephalin gene. [Met]-enkephalin is Tyr-Gly-Gly-Phe-Met. [Leu]-enkephalin has Leu in place of Met. Dynorphin is the product of a third opioid gene, called prodynorphin.
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 POMC which is the precursor hormone for adrenocorticotrophic hormone (ACTH), so it will be released whenever ACTH is released. The behevioral 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.
Beta-endorphin has the highest affinity for the Mu1-opioid receptor, slightly lower affinity for the Mu2 and Delta-opioid receptors and low affinity for the Kappa1-opioid receptors. Mu receptors are the main receptor through which morphine acts. Classically, Mu 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 an 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 chili peppers) also has been shown to stimulate endorphin release. Topical capsaicin has been used as a treatment for certain types of chronic pain. [How to reference and link to summary or text]
The placebo effect has been linked to endorphins. In one study, a volunteer received pain by a compression cuff on his arm. In the first trial, no drug was administered and the patient showed signs of pain including facial grimace, increased blood pressure, and sweating. During the next trial, the physican informed the volunteer that he would be injected with morphine and that he would feel no pain. The morphine was injected, the pain compression repeated, and this time the volunteer showed and reported no pain. The morphine and compression was repeated several times. Then, the volunteer was unknowingly injected with a saline placebo, but still reported no sign of pain, though the last time he was unmedicated the signs of pain were obvious. In a last test, the patients’ ‘morphine’ was actually an injection of naloxone, an opioid antagonist. Even though the volunteer believed the shot was morphine and expected relief, the endorphins’ effect was blocked by the naloxone injection and the volunteer displayed the same signs of pain as the first unmedicated trial. (Groopman 169)
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 if it is difficult to breathe. This also corresponds with the time that muscles use up their stored energy and begin functioning without oxygen. Workouts that are most likely to produce endorphins include running, swimming, cross-country skiing, bicycling, aerobics, or playing a sport such as basketball, soccer, or even 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. (Klosterman) (Altman) There is some recent evidence that endogenous cannabinoids are responsible for "runner's high", rather than endorphins. (Endocannabinoids and exercise, by A Dietrich and W F McDaniel, May 4, 2004 bjsportsmed.com)
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. However, skeptics say that not all studies point to that conclusion, and that in a trial of chronic pain patients, endorphins did not produce long-lasting relief. (Margolis 140-141).
The good feeling achieved during sex has also been attributed by some to the release of endorphins. [How to reference and link to summary or text]
- Altman, Nathaniel. “Endorphins Q & A.” 2002. <http://www.healingsprings.com/Endorphins.htm>.
- Fries, DS (2002). Opioid Analgesics. In Williams DA, Lemke TL. Foye's Principles of Medicinal Chemistry (5 ed.). Philadelphia: Lippincott Williams & Wilkins. ISBN 0-683-30737-1.
- Goldberg, Jeff (1988). Anatomy of a Scientific Discovery. Bantam Books, 1988. ISBN 0553346318; ISBN 0553176161 (British edition); ISBN 0553052616 (hardcover).
- Groopman, Jerome. The Anatomy of Hope. New York: Random House, 2004. 169-173.
- Klosterman, Lorrie. “Endorphins: The Gift You Give Yourself.” Chronogram. Nov 2005. <http://www.chronogram.com/issue/2005/11/wholeliving/index.php>.
- Margolis, Simeon. The Johns Hopkins Medical Handbook. New York, NY: Redley, 1995. 140-141.
- Simantov, R. & Snyder, H. (1976). Morphine-like peptides in mammalian brain: Isolation, structure elucidation, and interactions with the opiate receptor. Proceedings of the National Academy of Sciences (USA), 73: 2515, 1976.
- Smith, Trenton & Tasnadi, Attila (2003). A Theory of Natural Addiction <http://repositories.cdlib.org/cgi/viewcontent.cgi?article=1002&context=international>
Analgesics (N02A, N02B)
Buprenorphine, Butorphanol, Codeine, Dextropropoxyphene, Diamorphine, Dihydrocodeine, Fentanyl, Hydrocodone, Hydromorphone, Ketobemidone, Levorphanol, Methadone, Morphine, Nicomorphine, Opium, Oxycodone, Oxymorphone, Pethidine, Tramadol, Tapentadol
|Salicylic acid and derivatives|
|This page uses Creative Commons Licensed content from Wikipedia (view authors).|