Ever wondered why stabbing back pain keeps one person from functioning and another with the same issue seems only minimally distressed? Or why two soldiers with the exact same wound has one recovering in months and the other suffering from excruciating pain for years?
Why the difference?
Why does pain hurt some more than others?
It now appears to be related to a single molecule under the control of a gene that acts like a dimmer switch. When it’s on the high or bright setting this gene excites sensory nerves and causes them to produce high levels of a chemical called BH4. The more BH4 in the system the more pain is felt. Lower settings block BH4, which results in lower pain levels.
“This is the first evidence of a genetic connection to the risk of developing chronic pain,” notes Clifford Woolf, Richard J. Kitz Professor of Anaesthesia Research at Harvard Medical School. “People who do not have a pain-protective variety of the gene, called GCH1, which controls production of BH4, feel the most pain. Those who inherit one copy from their parents, about 25-30 percent of us, receive enviable protection. Those who are born with two such gene forms, one each from their father and mother, are the luckiest. They comprise about 2-3 percent of the population.”
But chronic pain is a complex trait, influenced by personal experiences, genetic, biological, psychosocial and environmental stressors. It often involves more than one part of the body. For example, fibromyalgia affects any and all areas, neck can coincide with low back and migraine pain. These chronic overlapping pain conditions (COPCs) are thought to be due to interactions between multiple genes and may be associated with the development of hypersensitivity to painful stimuli.
After studying twins it was estimated that 22-55% of what we perceive as pain is genetically modulated. So affecting those pathways could significantly alter how we perceive pain.
Other exciting findings show gene- SCN9A- encodes the complex molecule NA y1.7. This is a sodium activated channel and a building block in how the nervous system works, predominantly found near peripheral nociceptors in the spinal cord, acting as a relay station. When activated sodium ions flood into a neuron it causes the cell to discharge a nerve impulse that then transmits and encodes pain signals between the cord and brain. Targeted treatments here could give substantial relief without altering brain function.
A mutation in the DRD1 gene was 33% more prevalent in those who felt pain at higher levels than others. A higher pain tolerance was also seen in individuals with variations in the P2X7 gene which is closely linked to the body’s immune responses and inflammation.
TRPV1, is a sensory neuron receptor that captures adverse stimuli such as heat and burning sensations produced in the body by chili peppers. It also releases neuropeptides that lead to inflammation and swelling within a nerve. Researchers have found a potential pain insensitivity mutation in the gene that encodes that protein. The key is turning off the pain without preventing life saving stimuli from getting through e.g. removing your hand from a hot stove.
This new research offers amazing information on why people feel pain differently. What I might call a “7” could be a “3” or tolerable to you. Especially since it’s estimated 25% of the country suffers from some form of chronic pain issues. Add to that the cost and collateral impact chronic pain causes, finding safer ways to modulate pain has to be a priority.
We are clearly effected by our genes and even our gender.
- Studies found women have a greater number of nerves in any given body part.
- Circulating estrogen levels may be the reason women report more pain than men.
- Women have a poorer response to pain medications, yet the majority of all research has involved men.
Whatever the source, scientists are scrambling to find ways to switch it off. The more we understand about pain and it’s impact, the more opportunities we’ll find to do just that. In the meantime we need to be better at understanding how pain affects each individual. Minimizing or diminishing someone’s agony is disrespectful and inappropriate. Helping those on the high end of the scale understand the pain may be exacerbated by issues no longer current or by their genetics can be emotionally freeing. Chronic pain involves far too may etiologies to be denigrated and relegated to only those deemed physically or emotionally weak, then ignored.
That makes finding a caring, understanding provider more important than ever. Not one that just hands out pain pills. Especially with what we know about their devastating effects, but those who encourage using all the pain relief options available. Exciting new treatments are coming, until then we don’t have to be at the mercy of our genes.
-https://idp.nature.com/authorize?response_type=cookie&client_id=grover&redirect_uri=https%3A%2F%2Fwww.nature.com%2Farticles%2Fd41586-018-04560-z
-https://www.news-medical.net/news/20230303/Gene-mutation-capable-of-regulating-pain-discovered.aspx
-https://news.harvard.edu/gazette/story/2006/11/sensitivity-to-pain-explained/
-https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4590159/