Did you know that pain, although unpleasant, is essential for our survival?
In fact, it’s precisely its unpleasant nature that makes it necessary.
Pain is defined as an unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage. For those unfamiliar with biological sciences, tissue damage refers to harm affecting the body’s tissues. In this blog post, we’ll focus mainly on physical and conventional damage.
Its function is clear: it signals the central nervous system—and the individual—that a part of the body has been injured or is at risk of injury.
That’s why it feels so unpleasant. Its purpose is to prompt the body to avoid pain as much as possible, and when it occurs, to care for the injured area to stop it.
Pain is a very complex topic. It’s not a quantifiable or measurable sensation like temperature or pressure. It has biological, psychological, and social components.
Henry Beecher, an anesthesiologist, demonstrated this in 1956 by comparing similar wounds in groups of civilians and soldiers. The soldiers requested fewer painkillers.
Even though the physiological pain was similar, its meaning was different. For the soldier, being injured meant being in a safe area, out of combat, and bearing the honor of the wound. For the civilian, it implied a waste of time and money with no benefit.
Pain Tolerance Is Genetic
However, in recent decades, it has become clear that the different perception of pain in response to the same injury has more layers than previously thought.
One of those layers, as we now know, is a person’s genetics.
Genes influence the development of the entire organism, including pain sensitivity, its manifestations, and how we respond to it.
Is the sensation of pain genetic?
Studies in siblings have shown that it is. Research comparing pain perception between fraternal and identical twins showed that the latter had more similar responses.
Twin studies have also shown that chronic pain has a heritability ranging from 27% to 59%.
There’s even a term—pain genes—used to describe genes that cause abnormalities in nociception (the conscious perception of pain) when functioning abnormally, or that are only expressed in anatomical areas involved in pain, like the neurons responsible for detecting it.
These genes can be divided into two categories: pain insensitivity genes and pain amplification genes. The former cause genetic diseases in which no pain is felt or there is a high genetic tolerance to pain. In contrast, the latter lead individuals to experience more pain than normal.
Monogenic Pain Insensitivity
- The SCN9A gene is probably the best-known. It encodes a voltage-gated sodium channel that’s especially important in sensory pain neurons for generating and transmitting electrical signals. Mutations in the SCN9A gene can result in individuals with limited or no capacity to feel pain. At least ten different variants are known to cause insensitivity.
- Hereditary Sensory and Autonomic Neuropathies (HSAN). This term refers to a group of disorders caused by rare genetic mutations that affect the peripheral nervous system. Several of these disorders share the inability to feel pain. Although all are monogenic, different genes can cause the same HSAN. In all cases, a single mutated gene is enough to cause the disease.
Fun fact: If you’ve seen the movie Novocaine, the main character’s condition is HSAN IV, Congenital Insensitivity to Pain with Anhidrosis.
- The PRDM12 gene. This gene is essential in the development of neurons involved in pain perception and is considered responsible for HSAN VIII. It was one of the most recently discovered and has the interesting trait of being expressed only in the peripheral nervous system. For this and other reasons, it has been proposed as a therapeutic target in chronic pain patients.
- The ZFHX2 gene. This gene encodes a protein that acts as a transcription factor regulating the expression of other genes. Interestingly, its mutation is dominant. In most pain insensitivity disorders, both copies of the gene must be abnormal—but with ZFHX2, a single copy is enough.
Monogenic Pain Amplification
- The SCN9A gene—remember it? We mentioned it earlier. Now you see why it’s so well-known—it doesn’t just cause pain insensitivity. Depending on the mutation, it can also amplify pain or cause chronic pain. Around 100 different mutations in this large gene are known to affect pain perception.
- The CACNA1A This gene is associated with multiple dominant neurological disorders. Not only does it increase pain perception—it also causes migraines. A real expert at making life miserable.
- The TRPV1 gene. This gene is more widely known because the receptor it encodes is crucial for the sensation of heat and is the reason why capsaicin—a compound found in spicy peppers—causes pain and burning. We now know it also plays a role in pain sensitization.
This gives us a general idea. Many other genes are involved in various ways. For example, the OPRM1 gene plays a role in pain regulation and is the main receptor for opioids. Mutations in this gene can make a person more or less responsive to many painkillers.
Genetic Testing for Pain May Be in Our Near Future
Why is pain genetics so relevant—not just individually, but for society?
Because pain is one of the main reasons people seek medical care today. At any given time, it is estimated that around 20% of the world’s population is suffering from pain, to varying degrees.
That’s one in five people.
And they will respond differently to pain and the treatments used to relieve it.
Not to mention all those affected by chronic pain with a primarily genetic cause.
Knowing the genes involved in the pain response allows us to identify new therapeutic targets and methodologies. Working with pain is one of the largest fields within pharmacogenetics.
Knowing that people can be genetically very different in how they process painful sensations—and in their compatibility with medications used to relieve them—makes personalized medicine essential. The use of pharmacogenetic reports, for example in chronic pain cases, could mean substantial savings of time and money, minimizing side effects.
Imagine performing a genetic test for pain medication—using the right drug at the exact dose.
That’s why we recommend taking every opportunity to learn more about yourself and your genome. tellmeGen’s DNA tests are an easy and accessible way to begin exploring that world.
