Analyzing CIPA in Depth and Its Alternative Treatments
A lot of people wish they couldn’t feel pain. Imagine if you never cried and you never felt pain, chances are you would feel invincible. However, how invincible would you really be if you couldn’t experience pain, which tells you when something is wrong? Pain is the body’s reaction to a negative stimulus; it lets us know that something is wrong. Individuals that can’t sense pain can break bones and they would never know anything is wrong. Along with the inability to sense pain, those with congenital insensitivity to pain and anhidrosis also experience the lack of sweat and tears. Sure, they may not cry or sweat, which may sound like a nice thing, but these bodily functions are important to us as humans as it helps us maintain homeostatic balance. A simple fever can kill a person who has this disease, and most die before the age of three due to the inability to tell if they have a fever.
Sensing pain is an ability controlled and maintained by our body’s nervous system.
Our brain has two basic components to it; the central nervous system, which is comprised of the brain and the spinal cord; and the peripheral nervous system, which is made up of the sensory and motor nerves that we find everywhere else in our body. These two systems interact in a way that the sensory nerves receive a stimulus and they transmit an impulse to the spinal cord, which then relays the message to the brain. Once the brain receives the message and its identified, it then sends an impulse back to the motor nerves, and we can then react to this stimulus from the beginning. While this may seem like a complicated process, it takes milliseconds to occur. Our body has specialized receptors that are only activated when we have an injury. These receptors are special pain receptors called nociceptors. These receptors send an immediate response to the brain whenever they are alerted from a possible dangerous stimulus. Now imagine if these nerves and receptors were damaged? We can feel a piece of glass or a rock, but we can’t feel the sensation of pain. This is dangerous because we are unable to detect what is actually harming our body. Situations like this are what people with congenital insensitivity to pain have to deal with on a daily basis.
Congenital Insensitivity to Pain and anhidrosis also referred to as CIPA is a genetic disease in which the afflicted do not experience pain nor are they able to produce tears and sweat. Many of the individuals with this disease end of dying early on, or cause themselves self-inflicted injuries for the duration of their life. CIPA is associated with a family of disorders called HSAN; those with these disorders have complications with recognizing pain and temperature. This disease is very rare and only about 100 cases have ever been reported internationally, with most of these cases residing in Israel, Ecuador, Sweden and Japan. This disease is caused by a genetic mutation, usually found on the first chromosome. In order to get this disease both parents must have the mutation on their chromosome, so they’re able to pass it down, meaning that this disease is autosomal recessive, and not x linked, which relates to the gendered chromosomes.
HSAN, which stands for hereditary sensory and autonomic neuropathy is the family of disorders that CIPA belongs to. About every 1 in 25,000 people are afflicted by HSAN, in which those affected by type IV are much more rare. Type IV is the most rare and the most severe due to the fact that this is the only type that causes the inability to sweat, and it is what we know as CIPA. Type II of HSAN is casually known as CSN, in which the individuals experience all the symptoms of someone with CIPA, however they are able to produce sweat. Before these diseases were properly investigated, most associated them to be a subtype of muscular dystrophy, due to the fact that the symptoms included progressive loss of muscle tissue and touch sensation. With proper genetic testing, we are able to locate the gene that is mutated, which gives us more insight into the disease.
Humans have two pairs of 23 chromosomes, one from each parent. Each chromosome carries hundreds of genes, which are just sections of DNA that code for certain proteins. One cell has around 6.4 billion bps of DNA. There is about 1 mistake per million of bps copied, which means there are about 6400 mistakes per cell. With these statistics it’s very probable that a mutation can occur. A mutation on the first chromosome is the culprit for CIPA. The NTRK1 gene is the gene that is mutated on chromosome one. This receptor gene is part of a nerve growth receptor family in which the receptors have ligands that include neurotrophins. Neurotrophins and their receptors play a major role in regulating development of both the central and peripheral nervous system. This receptor is able to start a chain of auto phosphorylation, which then sends a signal to the brain. When someone has CIPA, this process is stopped and the signals of pain received are unable to relayed to the brain, so they are unable to react. Studies show that those afflicted with CIPA have a decrease in these nerves or a complete absence. CIPA doesn’t have a real uniform pattern; some may be worse off than others, such as the symptom of mental retardation.
Living with CIPA is not easy. Imagine having to be careful with everything you do, and having to rush to the ER if you ever fall, just to make sure nothing is broken. You would live your whole life overly cautious about the way you perform daily activities. As a child, it is difficult for a parent and the doctor to come to the diagnosis of CIPA. However the signs of being insensitive to bad falls, teething, bruises, etc. helps lead parents and doctors into the direction of CIPA. Teething can be a huge indicator of the disease, because those afflicted tend to chew on their tongues and lips and since they don’t feel pain, they will continue to self mutilate them. Another hard task for those with CIPA would be eating. We feel hunger pains that remind us to eat or remind us that we skipped a meal. Those affected by the disease can easily forget to eat and become malnourished because the hunger pains don’t exist. Going to the bathroom or timing when you have to go is also difficult. Without feeling pain it’s hard to tell when they need to use the restroom, as a result children can suffer from incontinence or constipation. The most dangerous part about living with CIPA is not just the insensitivity to pain, but the inability to sweat. Without the ability to sweat those growing up with CIPA can easily overheat, which is why so many die at a young age or experience febrile seizures.
There are not many treatments for this genetic disease, but research has indicated that a medication called naloxone may help with some symptoms. Naloxone is an opioid antagonist drug that was developed by Sankyo in the 60’s. It blocks agonist mediated responses to opiates, and is usually used to reverse the effects of an opiate overdose, such as heroin. It’s only recently been used to experimentally treat CIPA
CIPA does not inherently lead to fatality, but the injuries that go untreated is what typically leads to death. The top causes for death of those with the disease are appendicitis, heat stroke, heart attack, dehydration, blood poisoning, and fever. Most of these can be prevented by drinking a large amount of water and getting constant check ups. However, situations such as appendicitis and heart attack may be a little more difficult to prevent or treat once its already happened. If the appendix has fully perforated, the individual doesn’t have a lot of time before the infection can spread throughout the bloodstream and cause death. It’s hard to catch incidents like this in time due to the fact the person is unable to feel the pain of the appendicitis so they’re unable to get to the doctor on time.
CIPA is a very rare disease that research is barely being conducted on. With more research being continued there is hope for those suffering from CIPA and other diseases from the family HSAN to live a more normal life.