Pain Sensitivity

A pulled muscle in the back or leg can send some of us to the couch for days whereas others seem to more easily recover. How can we explain differences in pain sensitivity and recovery? Could the answer be in our genes? Scientists have been studying the question for a long time and the answer is: “it’s complicated”. Susceptibility to pain appears to be dictated by interactions between your environment and your genetics.

Fight…. or flight!

Many of the genes found to be associated with pain sensitivity contribute to the production of adrenaline and serotonin [1] Jump to reference section: [1] .

Both adrenaline and serotonin are 'neurotransmitters', which act as messengers in the brain to carry information. Adrenaline is often known as one of the “stress hormones” and is responsible for the famous “fight or flight response”. Increased levels of adrenaline raise the heart rate, elevate blood pressure and boost energy supplies. In other words, adrenaline prepares the brain to react to immediate danger. In patients with chronic pain, some genetic variants have been found on a gene called COMT, which is known to be involved in the regulation of adrenaline. Genetic variation in the site called rs4680 has been associated with different levels of susceptibility to chronic pain. People with two G's in this position are much more tolerant to chronic pain!

Genetic variation in another gene called ADRB2 also influences adrenaline levels and has also been suggested to play a role in pain sensation. One genetic variant near ADRB2 has been associated with chronic pain: rs1042713. Curiously, the adrenaline related genes mentioned in this article may also be associated with sleep dysfunction and anxiety.

Pleasure or pain?

The second neurotransmitter system that seems affected in patients with chronic pain is the serotonin pathway. Serotonin is often prescribed as an anti-depressant and is popularly thought to contribute to feelings of well-being and happiness. This description does not do serotonin justice, as it does far more in our body than regulate emotions and works in complex and intricate ways. In the context of pain for example, serotonin can act as an analgesic (painkiller) or as hyperalgesic (pain enhancer), depending on where it acts in the body. Several genes controlling serotonin production are involved in susceptibility to pain. The HTR2A gene codes for a protein that acts as a 'landing pad' or receptor for serotonin. The serotonin transporter gene SLC6A4 is also involved in pain perception. If you have two C's at rs25531, you are more likely, on average, to be more sensitive to thermal pain (such burns or frost bites).

What does this tell us?

This is only a snapshot of the many genes that are involved in pain sensitivity. It is important not to forget that the perception of pain can also be influenced by psychological factors. A recent study suggested that swearing out loud while immersing your hand in cold water can help relieving the pain [2] Jump to reference section: [2] . Overall, more research is needed to truly understand the biological nature of pain. As our understanding improves, there may be opportunities to develop more personalised treatments to acute and chronic pain.