The Molecular Nature of Pain

The human body, like any other higher-order biological system, is less of a single entity and more like a symphony composed of a huge number of moving parts. Each one of us is made up of trillions of cells, and each cell, in turn, is made up of trillions of molecules. Accordingly, everything our bodies do on a daily basis from circulating blood to absorbing nutrients boils down to some molecular mechanism of action in the end. Whether we know what these molecules are or how they are acting, of course, is another matter, but recent scientific advances have brought us a long way in these efforts. So what do we understand about the molecular nature of pain? Is there a single “pain molecule” responsible for every painful sensation we feel? It turns out that the process is slightly more complicated than that, but we still understand a great deal about the basics. In this article, we’ll take a brief look at pain and pain medication on the molecular level.

The technological term for pain detection is nociception, a process carried out by pain receptors called nociceptors. Nociceptors are a type of nerve fiber that detect intense stimuli of three types – mechanical (such as a tear), thermal (burning or freezing), and chemical (acids or bases) – and transmit a signal to the brain by way of the spinal cord. These nociceptors are further divided into classes based on the types of pain they conduct and at which speed: thresholds for heat or mechanical stress vary by class, as do the rate at which they transmit the signal to your brain. How localized the pain is to one area also affects the type of nociception. In other words, the signal that makes you draw your hand back from a red-hot burner is different from the one that tells you that you have a cut on your hand. Similarly, the signal that tells you that your chest is covered in sunburn from a day at the beach is different (and slower) than if a fleck of boiling grease hits you.

As these pain sensations are transmitted through nerves, slowing or otherwise reducing that transmission is an obvious target for pain medications. This is where opioids such as morphine or oxycodone come in. There are three well-known opioid receptors (DOP, MOP, and KOP, for Delta/Mu/Kappa OPioid) that are distributed throughout the nervous system, specifically residing in the cell membranes of neurons as transmembrane proteins. When opioid molecules bind to these receptors, they initiate a cascade of biological signals within the cell that ultimately reduce the transmission of nociceptive signals to the brain. Unfortunately, since these receptors are also in other parts of the body such as the digestive system and heart, they may have off-target effects such as nausea, slower heart rate, or respiratory depression.

What about other means of reducing pain? Inflammation is a common side effect of tissue injuries and source of pain when inflamed tissue affects nerve endings, but involves completely distinct pathways and molecules than simple nociception. For this reason, targeting inflammatory processes independently of nociception is a similarly worthy undertaking for pain research – and it has already been done in the form of NSAIDS (Non-Steroidal Anti-Inflammatory Drugs) such as Ibuprofen/Motrin. When tissue is damaged, the molecules in the cell membranes surrounding the damage may be scattered or leak into the bloodstream. One of these molecules, arachidonic acid, is metabolized by enzymes into a variety of signaling molecules known as prostaglandins. These prostaglandins go on to initiate the key events of inflammation that we recognize: redness, heat, swelling, and pain. By inhibiting the enzymes responsible for producing prostaglandins, we are able to significantly reduce tissue inflammation.

This has only been a brief safari into the jungle of molecular biology, but as with all things, knowledge is power – and having an idea of the molecular nature of common physiological processes can be quite helpful when determining new courses of treatment or research. Talking to your doctor or other similar professionals may also help determine the best plan of action. In the end, whether it is simply because you want to know more about your body or because you are experiencing certain symptoms, it never hurts to look into the science behind it.

References:

Basbaum, Allan I. et al. “Cellular and Molecular Mechanisms of Pain.” Cell 139.2 (2009): 267–284. PMC. Web. 11 July 2018.

Pathan, Hasan, and John Williams. “Basic Opioid Pharmacology: An Update.” British Journal of Pain 6.1 (2012): 11–16. PMC. Web. 11 July 2018.

Ricciotti, Emanuela, and Garret A. FitzGerald. “Prostaglandins and Inflammation.” Arteriosclerosis, thrombosis, and vascular biology 31.5 (2011): 986–1000. PMC. Web. 11 July 2018.

Jonathan Arthur