Of endorphins

Litde is known about metaboHc inactivation of ( -endorphin and the dynorphins. NEP, and to a lesser extent APN, are only weaMy active against P-endorphin (183). Enzymes are known which degrade P-endorphin in vitro under nonphysiological conditions (202) or which inactivate P-endorphin by N-acetjlation (203). Alack of specific degradative enzymes for these peptides may account for their relatively long half-life in vivo though this has not been definitively estabUshed. 

Olive MF, Koenig HN, Nannini MA et al (2001) Stimulation of endorphin neurotransmission in the nucleus accumbens by ethanol, cocaine, and amphetamine. J Neurosci 21 1-5... 

Dronabinol (tetrahydrocannabinol), the active principle from cannabis and synthetic cannabinoids, nabilone and levonantradol are effective in treating nausea and vomiting in cancer chemotherapy. The mode of action is unclear but appears to involve cannabinoid CBi receptors. Cannabinoids have been shown to reduce acetylcholine release in the cortex and hippocampus, and have been suggested to inhibit medullary activity by a cortical action. Inhibition of prostaglandin synthesis and release of endorphins may also be involved in the antiemetic effect. A review of trials of dronabinol, nabilone or levonantradol concluded that while the cannabinoids were superior to placebo or dopamine receptor antagonists in controlling emesis... 

When Montgomery and I published our article, we thought we had disproven another theory of placebo effects - the theory that placebo effects are produced by the release of endorphins in the brain. In 1978 researchers at the University of California in San Francisco discovered that when placebos reduce pain, they may stimulate the release of endorphins.18 Endorphins, the existence of which had only been discovered a few years earlier, are opioids that are produced naturally by the brain. Just like the opiates that are derived from opium - morphine and codeine, for example - endorphins reduce the sensation of pain. The University of California researchers reasoned that if placebos can mimic the effects of opiate drugs, maybe they do so by stimulating the release of the brain s endogenous opioids. 

How does physical exercise alleviate depression One possibility is that it increases the release of endorphins that produce a sense of well-being, sometimes referred to as the runner s high . Another possibility is that it is a placebo effect. But even if it is a placebo effect, consider the differences between exercise and antidepressants in side effects. Side effects of antidepressants include sexual dysfunction, nausea, vomiting, insomnia, drowsiness, seizures, diarrhoea and headaches. Side effects of physical exercise include enhanced libido, better sleep, decreased body fat, improved muscle tone, greater life expectancy, increased strength and endurance and improved cholesterol levels. So if both antidepressants and exercise work by means of the placebo effect, which placebo would you prefer ... 

Signals from pain receptors are transmitted to the brain where they are processed in the thalamus and then passed on to the sensory cortex where the sensation of pain originates. Receptors for endorphins (and for the opiates) are abundant in these regions and it is likely that a natural role of endorphins is to interfere with the transmission of impulses through these regions. The opiates appear to do the same, acting not so much to alter the pain threshold but altering the patient s attitude to pain. 

So, there s actually a biological basis to the euphoric sensation associated with high-level physical activity, such as the runner s high described by long-distance runners and exercise gurus The euphoria is caused by the body s release of endorphins and enkephalins produced by prolonged exercise or stress on the body. 

Endorphins likely came first, and then humans made the discovery of how opium contains compounds that mimic the effect of endorphins. Thus, opioids have endorphin activity. Why this is so is something you should be sure to discuss with your instructor. 

Methadone and opiates were first used for pain relief, and are still chiefly used in that area of medicine. It is important to remember that methadone and other opiates do not exert their pain control by altering a person s sensitivity to pain. Rather, methadone and other opiates interfere with the transmission of pain impulses from the nervous system to the brain. They accomplish this by a variety of methods. First, they decrease the transmission of nerve signals that conduct pain messages from various parts of the body to the spine. Secondly, they prevent production of neurochemicals that transfer this pain information to the spine. Finally, they mimic the actions of endorphins, which are the body s own pain-controlling chemicals. While methadone and other opiates work quite well to control pain, they do not affect touch, vision, or hearing. 

Trypsin cleaves peptides at the carboxyl side of Lys and Arg. The only fragment that does not end in Lys is the dipeptide. Therefore, it must come at the C-terminus of endorphin, and the C-terminal amino acid is Gin. 

Endorphins were discovered when scientists found sites where molecules such as morphine bind to nerve cells and reasoned that the body must use these sites to bind chemical compounds. Experiments showed that the compounds were small peptides, and the actions of endorphins were determined by a number of researchers. 

The discovery of endorphins also raises interesting questions. Why have the human brain and the poppy evolved chemicals with similar effects when they are so unlike each other Is this fact a mere coincidence or does it suggest a deep relationship between people and plants that underlies the age-old inclination to experiment with vegetable drugs And what does it say about the "nat-... 

For example, in certain cultures specific rites and rituals may involve a pain that is readily accepted by the people within that particular society. Scientists believe that people in these cultures experience that pain to a far lesser degree than others from different cultures would if they underwent the same experience. In such cases, the ability to focus on other aspects of the ritual, such as its social or religious ramifications, may act as a psychological sedative that helps the individual better tolerate the pain or, perhaps, feel no pain at all. The expectation of pain also determines how much pain is felt. Two people, for example, may go to the dentist the person who has greater anxiety about the experience is likely to feel a greater amount of pain. Tension and emotional states may also cause biochemical changes that lower the amount of endorphins (naturally occurring opiates) produced by the brain. 

Transcutaneous electrical nerve stimulation (TENS) helps some sufferers it may act by promoting the release of endorphins. Ketamine (see p. 353) or lidocaine (Ugnocaine) (by i.v. infusion) are used in special circumstances. Pain due to nerve compression may be reUeved by a corticosteroid injected loccally. 

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