House M.D. and The Girl Who Felt No Pain: A Look Into CIPA

Season three, episode fourteen of House M.D. introduces the audience to a peculiar girl. She does not appear to mind freezing cold water, flexes her open injury towards an alcohol cleaning pad, and most importantly, violently denies that she has a condition called CIPA.

House realizing his patient has CIPA, House M.D. Season 3, Episode 14

So, what is CIPA?

Congenital Insensitivity to Pain with Anhidrosis is a genetic disorder that renders an individual unable to feel pain, temperature, and unable to sweat. Compared to other genetic disorders, this one may not sound as impactful at first glance. However, this condition is much, much more dangerous. Pain is the body’s way of signaling to the brain that there is something wrong. For instance, we instantly withdraw our hands if we come into accidental contact with a blazing hot liquid or surface, but people with CIPA don’t have that warning flare, potentially leading to catastrophic burn damage. Another aspect is the delayed diagnosis of certain illnesses. CIPA patients are not going to be aware of conditions such as ulcers or appendicitis until it reaches a critical stage, as they will have no indication that they are afflicted.

This disorder is even more deadly for children. The girl in the episode had scarring around her lips and tongue, which were signs of CIPA. Kids with CIPA are prone to unintentional self-harm, since they cannot feel pain. There is nothing stopping them from severely chewing on their tongue, fingers, lips, or other parts of their bodies. They may also pick at open wounds and not let injuries heal properly, leading to possible infection, disfigurement, or even spontaneous amputation.

Worse, the inability to sweat leads to the huge risk of overheating. Sweat is the body’s natural coolant system, so CIPA patients are at extremely elevated risks of heatstroke and dangerous fevers, especially in children.

How exactly does this mutation cause all of the body’s pain receptors to stop functioning? CIPA is the result of a mutation in the gene NTRK1. Normally, this gene codes for a receptor protein called tropomyosin receptor kinase A (TrkA). Normally, TrkA binds to another protein called nerve growth factor beta (NGFβ), triggering a phosphorylation cascade that regulates the survival, growth, and proliferation of nerve cells. In other words, it is essential for the development and survival of several types of neurons, including those responsible for pain sensation and sweat gland signaling.

The mutation of the NTRK1 gene leads to the loss of function of the TrkA protein, changing its shape and preventing it from properly binding to the NGFβ protein. This cripples all neurons that depend on NGFβ to survive, especially primary efferent neurons, the neurons responsible for pain sensation, and cholinergic neurons, the neurons who are mainly responsible for sweat gland activation through the release of acetylcholine, a neurotransmitter that signals to receptors on sweat glands to produce sweat.

How rare is CIPA?

There are only a few hundred documented cases of CIPA worldwide. It cannot be transmitted from individual to individual, as it is a genetic condition. Its inheritance follows the autosomal recessive pattern, which means in order for a newborn to have the condition, both parents must each have a copy of the mutated gene, and even then both copies of the gene have to be inherited (25% chance).

CIPA may initially seem like a real superpower, promising a life without pain or discomfort, but in reality it is a life-threatening condition. The ability to feel pain and temperature are two of the body’s most crucial warning systems, and without them people are rendered unaware to potentially fatal injuries and illnesses if left unchecked.