A World Without Pain
Two parents bringing a newly born baby into the world will likely warrant some crying as the baby takes their first breath. It's even expected they cry, likely due to the discomfort of opening their newly formed lungs for the first time or feeling too hot wrapped in all the blankets. But for one couple, their baby just seemed like the happiest baby in the world. Neither hunger nor wetting provoked any sort of response for this baby, and after few weeks, not even a painfully looking bloodshot eye showed a sign of discomfort.1 To some, this might start to raise concern and further testing was done. It turned out that their baby girl had a condition known as congenital insensitivity to pain with anhidrosis (CIPA) that fewer than 100 children in America have, resulting in insensitivity to pain and temperature.1 This baby’s lack of crying associated with pain and discomfort produced no type of behaviour that might alert the parents of her discomfort, and because of these deficiencies in sensation, CIPA often manifests complications that can be more lethal than the disease itself.2 We now know pain plays its role in helping us avoid self-damaging behaviours by encouraging self-protecting ones.3 Pain also alerts us to injury, and the unpleasantness associated with it allows us to learn to avoid facing imminent harm in the first place. Leading psychologists agree that there is no other substitute for unpleasant sensations to encourage life-saving behaviours similarly, meaning pain has to be unpleasant to serve its function.2 For these reasons, CIPA can easily manifest undesirable complications for patients and their families, but with a proper understanding of the disease, it can be a manageable condition that individuals can learn to cope with.
We can start to understand the pathology of CIPA by first looking at the normal physiology of our sensory organs. The nervous system builds our overall perception of the world by integrating information from all senses and modalities of the human body, where each modality detects a unique feature of a sensation.4 For example, in evolutionary history, touch diverged into distinct modalities that let us distinguish between things like fine touch and crude touch, texture and vibration, or hot and cold.5 Without the evolution of that neural pathway into all these distinct modalities, we likely wouldn't be able to work with our hands as efficiently as we do today. Fine touch, among other higher order modalities of touch, have evolved more recently and as such, contain unique parts that distinguish them from the more primordial modalities such as pain and temperature that evolved earlier in evolutionary history.5 The neurons that detect pain and temperature share certain similarities like the use of the protein nerve growth factor (NGF) for neuron survival and maintenance, likely because they evolved around the same time.3 The gene that produces the NGF protein, NTRK1, can sometimes be altered to the point where insufficient NGF protein is produced, and as a result, children don’t develop these sensory neurons.3 Patients with CIPA still retain all other modalities of touch, including vibration, proprioception, and basic touch. But without neurons that require NGF, patients are incapable of sensing pain and temperature as well as sweating because the neurons that innervate sweat glands also rely on NGF, ultimately giving rise to CIPA.
At birth, several signs of CIPA can become evident that would warrant further neurological testing. Firstly, excessive biting of the tongue, lips, and fingers to the point of bleeding may occur at an early age once the infant begins teething.3 Any signs of delays in intellectual milestones or the absence of sweating may also indicate the need for further testing.3 A neurological exam would then be conducted to observe certain withdrawal behaviours when painful stimuli are applied to the skin, and if no such responses are reported, then genetic testing is done to search for the presence of an NTRK1 gene variant, which would confirm the diagnosis of CIPA.3
It might be difficult to imagine what not being able to feel pain might feel like. The symptoms themselves are not lethal; so many children might misinterpret this as an opportunity to appear indestructible like their favourite superheroes. But this mentality may falsely lead patients with CIPA into thinking they are incapable of getting hurt, when in fact, many patients die most often because they were hurt internally or externally but incapable of knowing it.2 Patients can inadvertently harm their body in ways similar to everyone else but are unlikely to let injuries heal or stay bedridden if they don’t feel something is wrong. When you can’t feel pain, you lack a key part of self-awareness that demands constant vigilance and attention from friends and family of the individual.
Currently, treatments are only palliative and fail to resolve the underlying cause of disease by only treating the complications that may arise. Complications often arise due to poorly healed wounds, bones, or organs that left unattended to could easily lead to death.2 Another concern for physicians dealing with CIPA patients is frostbite in addition to hyperthermia because body temperature is poorly regulated due to the nerves that activate sweat glands requiring the NGF protein.3 Without sweating to help regulate body temperature by expelling heat in the form of water, it becomes especially difficult for patients with CIPA to regulate their body temperature, therefore making room temperature another important consideration for supporting friends and family. A potential therapy to prevent injury from patients biting themselves is dental management. The degree of intervention with this approach varies depending on the age and severity of the condition, but can be as minor as mouth guards while sleeping or as severe as complete dental removal.2 This can be rather invasive and unnecessary for most patients, making environmental consideration the predominant form of palliative treatment because as of yet, no curative treatments are available.
For many years now, leading researchers in the field are still trying to devise better ways to screen for CIPA earlier and treat it before the underlying pathology can take place. Until then, proper consideration of a patient’s deficit in self-awareness can help manage the overall condition. Attending to the complications that arise and managing the environment of patients with CIPA can prove to be sufficient for individuals to live out their lives without the ability to feel pain and temperature.2 This way, parents raising a child with CIPA can still raise them to live a life where their condition doesn’t hinder them.
1. Daily Mail Reporter. Ashlyn Blocker defies odds to live with rare genetic disorder CIPA that kills most before age of three | Daily Mail Online. July 6, 2012. http://www.dailymail.co.uk/news/article-2169530/Ashlyn-Blocker-defies-odds-live-rare-genetic-disorder-CIPA-kills-age-three.html.
2. Schalka MMS, Corrêa MSNP, Ciamponi AL. Congenital insensitivity-to-pain with anhidrosis (CIPA): A case report with 4-year follow-up. Oral Surgery, Oral Med Oral Pathol Oral Radiol Endodontology. 2006;101(6):769-773. doi:10.1016/j.tripleo.2005.07.030.
3. Indo Y. Nerve growth factor and the physiology of pain: lessons from congenital insensitivity to pain with anhidrosis. Clin Genet. 2012;82(4):341-350. doi:10.1111/j.1399-0004.2012.01943.x.
4. Bigley GK. Sensation. Butterworths; 1990. http://www.ncbi.nlm.nih.gov/pubmed/21250231.
5. Kaas JH. Evolution of somatosensory and motor cortex in primates. Anat Rec. 2004;281A(1):1148-1156. doi:10.1002/ar.a.20120.
Cite This Article:
Hamadeh Z., Chan G., Palczewski K., Lewis K., Ho J. A World Without Pain. Illustrated by C. Scavuzzo. Rare Disease Review. April 2018. DOI:10.13140/RG.2.2.17164.21121.