A Painless Life – a Curse or a Blessing?
Can the study of a medical condition causing the inability to feel pain help us advance pain management research?
Season 3, Episode 14 of the medical drama series House, playfully named “Insensitive”, tackles the case of a teenager with a genetic inability to feel pain. As the medical team attempts to help Hannah after a nasty fall on ice she suffers second degree burns on her hand, jumps from a balcony railing breaking several bones and suffering a concussion, and finally has a huge tapeworm removed from her abdomen – all without anaesthesia or any pain. Hannah’s story may be fictional, but it reflects the reality of a few hundred people worldwide, who live a pain-free life.
Congenital insensitivity to pain with anhidrosis (CIPA) is an extremely rare and dangerous hereditary disorder where the person’s nervous system is unable to process pain or temperature.2 People with CIPA commonly have a genetic mutation in the NTRK1 gene, meaning they lack the proteins that are responsible for building the pain and temperature-processing nerve cells in the parts of the brain that receive these messages.
Underdeveloped sensory nerves mean that people with this condition can’t regulate their body temperature, which can lead to heat stroke or seizures, lack protective impulses and suffer from joint and bone problems caused by repeated injury. In early years, some may also present with learning difficulties, hyperactivity and cognitive impairment. A genetic test is required to confirm the diagnosis, but CIPA is often diagnosed in early childhood when the child doesn’t show a typical pain response, like wincing during vaccination or crying after a fall.
The disorder was first described in 1953 in an American middle-aged ticket salesman, with more cases popping in medical journals worldwide over the next 70 years. Due to its rarity and complicated mechanism, there is unfortunately no treatment for CIPA.
In theory, the ability to live pain-free is a fascinating superpower, but case studies tell us this is more of a curse rather than a blessing. A 2019 study published in The British Journal of Anaesthesia described the story of Jo Cameron, a former Scottish teacher, whose DNA sequence was found to contain two mutations.3 Together they suppressed pain and anxiety, meaning she experienced broken bones, birth and a hip replacement with little to no reliance on painkillers.5,6 There are a few more stories similar to Jo’s, describing mysterious cuts, bruises, burns, breaks and confused parents and doctors.4 While the names, specific genes and injuries may vary, they all boil down to families that reconciled themselves to endless tests and the realization that they lack a safety net that helps protect themselves from the world.
The inability to feel pain invites us to reflect on the significance pain has in our own lives. It’s a constant of life that connects many critical works of philosophy, literature and religion. Feeling pain is being human. From an evolutionary standpoint, pain plays a fundamental biological function in alerting us to threats to our survival. In the past this would be predatory attacks, environmental hazards or illness. In other words, it lets us adapt our behaviour to keep us safe. Hence, one potential explanation behind the low incidence rate is that without the body’s natural warning system, many CIPA patients never reach adulthood, either due to unrestrained self-destructive behaviour or are driven to suicide to escape a low quality of life.2 Painless does not mean joyful.
Stories from people like Ms. Cameron and others are a reminder of how a medical anomaly can bring about scientific ingenuity. Pain management is a huge market for the biopharma industry, profiting companies billions every year. Amid the devastating drug addiction crisis and the race to find the next big painkiller, researchers are searching for alternatives to addictive opioids that are more effective for severe pain than the humble aspirin. By the studying the pain-free community, scientists are hoping to find a much-needed breakthrough in our understanding of pain management, especially for people on the other end of the pain spectrum – those with chronic pain.
While pain research and chronic sufferers may benefit from the uniqueness of a pain-free disorder, CIPA patients themselves are unlikely to reap the benefits. The low incidence rate and lack of scientific advancement means that there is no financial motivation for designing gene therapy to correct the mutation and return the feeling of pain. But medical experts remain hopeful that these studies may produce a new diagnostic test that allows early detection of CIPA and new strategies for management of the disorder.1
While studying pain management is an important branch of research, improving quality of life in CIPA patients should be also given priority. For now, we hope that those with CIPA may also one day understand pain as more than just an abstract idea. Perhaps relate to the feeling of hitting your elbow on the edge of your desk, scraping your knee after falling off a bike or scalding the roof of your mouth on a hot cup of tea in the morning.
Sources:
1 Cox, D. (2022) The curse of the people who never feel pain, BBC News. Available at: https://www.bbc.com/future/article/20170426-the-people-who-never-feel-any-pain (Accessed: 11 March 2024).
2 Daneshjou, K., Jafarieh, H. and Raaeskarami, S.-R. (2012) Congenital insensitivity to pain and anhydrosis (CIPA) syndrome; a report of 4 cases, Iranian journal of pediatrics. Availableat:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3564101/#:~:text=Background,and%20damages%20to%20oral%20structures. (Accessed: 11 March 2024).
3 Habib, A.M. et al. (2019) ‘Microdeletion in a faah pseudogene identified in a patient with high anandamide concentrations and pain insensitivity’, British Journal of Anaesthesia, 123(2). doi:10.1016/j.bja.2019.02.019.
4 Heckert, J. (2012) The hazards of growing up painlessly, The New York Times. Available at: https://www.nytimes.com/2012/11/18/magazine/ashlyn-blocker-feels-no-pain.html (Accessed: 11 March 2024).
5 Murphy, H. (2019) At 71, she’s never felt pain or anxiety. now scientists know why., The New York Times. Available at: https://www.nytimes.com/2019/03/28/health/woman-pain-anxiety.html (Accessed: 11 March 2024).
6 Sample, I. (2019) Scientists find genetic mutation that makes woman feel no pain, The Guardian. Available at: https://www.theguardian.com/science/2019/mar/28/scientists-find-genetic-mutation-that-makes-woman-feel-no-pain (Accessed: 11 March 2024).