Captioning By: Cameron Young On mile 14 of his run, Holden is extremely tired and sore. He’s been running for almost two hours now, but is pushing to complete a marathon. All of the sudden, his pain feels like it’s been lifted, and a calm has settled around him He’s experiencing what’s known as a “runner’s high,” which is made possible, in part, by the opioid receptor. The opioid receptor exists specifically to numb pain in the body. When in pain, the body releases its own chemicals that attach themselves to the opioid receptor, which then blocks the pain signal. This trait was developed by evolution, as numbing extreme pain in the body would allow humans to escape from dangerous situations, like, in a situation where you break a bone while running from a predator, it’s better (in that instant) to escape from the predator and not die than it is to tend to your broken bone. This is also where the “runner’s high” comes from. When running long distances, the body assumes that you must be running from something very dangerous, and releases the same chemicals to numb whatever soreness you have, releasing the “Happy Chemical” dopamine at the same time. Opioid receptors work through a method known as “Ligand-Binding.” Ligand is just another word for “chemical messenger,” which are (in this case) opiates. When opiates enter the body, they make their way to the brain and bind to the opioid receptors, which are implanted in the membrane of brain cells. When this happens, the receptor protein changes shape in what is
known as a “Conformational Change.” Opiate drugs are able to do this because they mimic the structure of the body’s natural pain relieving chemicals. Specifically, opioids form a T-shape with their carbon rings, and all contain a positively charged nitrogen atom. Chemicals that use this type of mimicry and cause a response are known as “agonists.” There are other types of chemicals, known as “antagonists,” that bind to the receptor but don’t cause a response. This is how the “save you from opioid overdose” drug Narcan works. On the inside of the cell on the membrane, there is a multi-protein structure known as a “G-Protein Complex.” This set of proteins is attached to an opioid receptor, and when the conformational change occurs, the complex breaks off of the receptor, and then breaks apart. The broken G-Protein Complex travels along the cell membrane to another protein also embedded in the cell membrane and stops it from sending the pain signal through the brain cell. Another part of the G-Protein Complex goes and signals the cell to begin sending out dopamine. Inside the cell, there’s a protein called “arrestin.” After the G-protein breaks off, an arrestin protein will come and bind to the opioid receptor. The binding of the arrestin promotes the creation of a little compartment that surrounds the receptor and pull it into the cell. The environment inside of this little compartment becomes more acidic, forcing the receptor to change shape. The opioid no longer fits into the receptor, and thus, it is released. Two possible steps occur after this. Either the receptor is returned to the cell membrane to be used again, or the receptor is broken down. The arrestin protein is responsible for building tolerance to opioids. This entire system is built to handle the body’s naturally produced opioid chemicals, and it does it’s job well. The problem of addiction occurs when using opioids that aren’t produced by the body. These opioid agonists bind much tighter to the receptor than the naturally occurring chemicals, so the cellular response of dopamine production and pain relief is increased a huge amount. This large release of dopamine causes the brain to experience a sense of euphoria that no runner’s high could ever compete with. After experiencing this euphoria even just once, many people become addicts, trying to experience that high once again. While for now, Holden is happy to be running, his body is working overtime to escape whatever dangerous predator must be chasing him. The same biological machinery that allowed our ancestors to survive predator attacks is now being used by addicts trying to get their fix.