How CIPA Works

Understanding CIPA

As we saw earlier, CIPA is part of a group of disorders referred to as HSAN, disorders that result in trouble perceiving pain and temperature. CIPA, or HSAN Type IV, is one of the most severe. It's the only HSAN that causes the inability to sweat.

HSAN II, or congenital insensitivity to pain, is a lot like CIPA. People with HSAN II, which is also called congenital sensory neuropathy or CSN, suffer from the same kind of profound sensory loss, but they retain the ability to sweat.

CIPA is an autosomal recessive disorder. This means that for someone to get CIPA, he must receive a copy of the gene from both parents. Each of those parents must have a mutation on an autosomal chromosome, the chromosomes that aren't related to gender. Research indicates that a mutation on the TRKA (NTRK1) gene, which appears to control nerve growth, may be the culprit. There are no reliable statistics on how many people have CIPA at this time, but the condition is quite rare. It does not seem to affect one gender more than another.

So how does not feeling pain work? First, let's learn a little bit more about the nervous system. Your nervous system is made up of your brain, cranial nerves, spinal cord, spinal nerves, and other bodies, like ganglia and sensory receptors. Your nerves are what carry messages from your body to your spine, and your spine carries the messages to your brain. If you cut your finger, receptors in your finger send a message through the nerves to the brain that tells it "Ouch!"

Your peripheral nerves are important to feeling pain. They end in receptors that sense touch, pressure and temperature. Some of them end in nociceptors, which sense pain. Nociceptors send pain messages in electrical impulses along the peripheral nerves, which then travel through the spine and then to the brain. Nociceptor axons are usually unmyelinated, which means that they are slow. Myelin is an insulating sheath that forms around nerves and helps with impulse conduction -- the more myelin, the faster the message. The axons that carry the pain messages from the nociceptors can be either myelinated or unmyelinated, which means that pain messages can travel quickly or slowly. Which path the pain message takes depends on the type of pain -- severe pain travels on the fast path, while lesser pain travels more slowly.

This process doesn't happen for people with CIPA. Studies have found that nerve conduction in people with CIPA appears to be fine, so it's not that the message is getting lost. Some studies have shown a decrease or absence of nerve fibers -- both unmyelinated and myelinated. Without those nerve fibers, the body and brain cannot communicate. Pain messages don't make it to the brain because no one is sending them.

People with CIPA are also missing a nerve supply (innervation) in the epidermis and the eccrine sweat glands. There are two types of sweat glands: eccrine and apocrine. Eccrine sweat glands are all over your body and are used for body temperature regulation. Because there are no nerves in the skin and sweat glands, there is no way for the body and the brain to communicate with one another, resulting in anhidrosis. (You can get a more in-depth in-depth look in How Sweat Works.)

CIPA doesn't have a uniform clinical pattern. For example, most people with CIPA have some form of mental retardation -- but not all. In some patients it's serious, while in others it's very mild.