How Genetics Affects Pain Tolerance

It is said that nobody experiences pain the same way. To some, a light punch in the shoulder can feel like almost nothing. To others, such a punch may sting for the rest of the day. For this reason, pain is very difficult to quantify, as there is no objective method for measuring pain (and for that matter, pain tolerance). This is why, when a doctor is assessing the amount of pain their patient is in, they will often ask the patient to rate their pain on a scale of 1 to 10, or use a similar scale which allows the patient to subjectively rank their discomfort. But one must wonder: why is it that some people can tolerate more pain than others? The answer may lie in their genetics.

The fundamental purpose of pain is to let your body know when something is wrong. It helps prevent you from seriously injuring your body, or further damaging any injured body part. The sensation of pain is caused by a series of neural pathways located throughout the peripheral nervous system, designed to detect damage to nearby tissue and send signals to the brain in response to such damage. Most forms of pain are detected by neurons located throughout the skin, muscle, and viscera of the body. These neurons have specialized nerve receptors designed to translate a variety of “noxious stimuli” (i.e. pain) into electrical signals, which are then sent to the brain. While most of these receptors are polymodal (meaning they can detect most forms of pain), some are designed only to detect one “type” of pain. For instance, there are nerve receptors designed chiefly to detect pain caused by heat, pain caused by cold, pain caused by tissue damage, etc. Once these nerve receptors have been stimulated, the damage will be transmitted to the brain via the spine through a series of ion channels. Unlike other senses, such as vision or hearing, pain does not have a specific region in the brain that is meant to process it. Rather, pain is processed via a “pain matrix,” a complex network of neural pathways located throughout the brain. These different biological process all combine to generate the sensation of pain.

Because pain is a very complicated sensation, with many different parts of the body ultimately contributing to the sensation, transmission, and processing of the pain, there are naturally many different genes whose presence (or lack thereof) can significantly alter the way one experiences pain. The primary parts of the body responsible for pain detection include nerve receptors which detect pain, the neural pathways which transmit pain, and the neurons within the pain matrix which process the discomfort. Thus, the genes responsible for the formation and maintenance of these parts of the body will be the genes which have the greatest effect on one’s pain tolerance. For example, the gene TRPV4 plays a significant role in the sensation of mechanical pain (pain felt from a force striking the body). A mutation that prevents this gene from being expressed would thus cause someone to feel significantly less mechanical pain than someone without the mutation. Because of the complexity involved in generating pain, there are over 50 different genes which affect pain tolerance, the mutation of any of which can result in a significant reduction in pain sensation.

There are many other factors which affect one’s pain tolerance. For instance, studies have shown that women tend to feel less pain than men, due to their higher levels of estrogen (which acts as a natural painkiller in the body). Psychology may also factor into how one processes pain. In one study, where all participants stuck their hands in an ice bucket until the pain overwhelmed them, one group was asked to imagine fantasies of a sexual nature while doing so, while another was asked to imagine fantasies of a neutral nature, and another was given no instructions. It was found that the positive emotions generated from the sexual fantasies resulted in a significantly higher tolerance to pain than those who did not experience such emotions. This supports the idea that one’s emotional state can affect the way they feel pain.

Ultimately, pain is a complex sensation. The number of different factors which can affect pain tolerance, genetic or otherwise, is too large to list in this article. Regardless, we are always looking for new, better ways to reduce pain, both chronic and acute. The only way we can do this is to understand the mechanisms through which pain emerges. Only then can we truly begin to treat our patients.                                                                                                                         


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“Why Does Pain Tolerance Differ Among People?” The Role of Sisterhood in the Goblin Market | Serendip Studio,

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George Galanis