It interferes with sleep, mobility, nutrition, thought, sexual activity, emotional well-being, creativity, and self-actualization. Congenital insensitivity to pain is a rare disorder, first described in by Dearborn as Congenital pure analgesia. Congenital insensitivity to pain and anhydrosis CIPA is a very rare and extremely dangerous condition. People with CIPA cannot feel pain [ 1 ]. Pain-sensing nerves in these patients are not properly connected in parts of brain that receive the pain messages.
CIPA is extremely dangerous, and in most cases the patient doesn't live over age of Although some of them can live a fairly normal life, they must constantly check for cuts, bruises, self-mutilations, and other possible unfelt injuries.
Self-mutilation is an almost invariable feature of this disorder, most often involving the teeth, lips, tongue, ears, eyes, nose, and fingers[ 2 — 4 ].
The odds of being born with this condition are about 1 in million. People with CIPA also cannot feel extreme temperatures, or sweat, both creating even more necessary care [ 5 — 7 ]. However, in a patient with CIPA, the gene encoding the Neurotrophic Tyrosine-Kinase receptor NTRK1 gene , is mutated in a way that interferes and halts the autophosphorylation process, therefore stopping signals of pain and temperature from being sent to the brain[ 8 ].
Case 1: A 12 year old boy presented with chronic osteomyelitis. He was the fifth child of a consanguineous Iranian couple. In his birth history he had low Apgar score. There was no familial or hereditary disease in the family. Pregnancy was normal. He had several hospitalizations because of fever, seizure, heel sores and osteomyelitis Fig. He had no reaction to pain and could not feel pain or heat. Brain CT scan and lumbar puncture findings were normal.
He is mentally retarded. Finger tip osteolysis right and painless heel sore left in a 12 year old boy with CIPA syndrome. We did our best to control the infection by administering appropriate antibiotics and by the debridement of necrotic tissues to avoid limb amputation and to keep his quality of life as good as possible.
He had also massive osteolysis in his mandible in which attemts were made for appropriate dental procedures. Obvious, self-mutilation, especially in his finger tips was observed.
Radiographies also revealed osteolysis in his digit rum Fig. The other sites such as lung, heart, abdomen and eyes were normal in physical examination. Case 2: A 13 year old girl was referred to our department because of purulent discharge from a deep sore in the talus and calcaneus of her right foot with history of recurrent osteomyelitis from the first months of life.
She suffered from the absence of normal reaction to painful stimuli or heat. She occasionally had hyperthermia, and convulsions, high fever with abnormal electroencephalogram EEG and received anticonvulsant drugs. There was no family history of special or hereditary diseases.
She was the second child of related first cousins parents. The patient had first experienced osteomyelitis when she was 3 years old in her buttocks and lumbar sites. Her last hospitalization was because of a resistant infection which did not respond to different antibiotics during the 3 preceding months. Because of a harmful deformity in her heel and ineffective antibiotics, after an orthopedic consult, an amputation was performed Fig.
Three weeks after the amputation, however, she came back with massive cellulitis in the site of surgery which progressed to the knee but she didn't feel any pain. Our case had also significant mandibular lysis and dental laisions. She was mentally retarded. Osteolysis on her fingertips was seen, but there was no sign of ocular disturbance Fig. They currently have three products in clinical trials in partnership with Teva and Genentech, one in phase two trials for shingles pain, and two more in the first phase of safety studies.
So you have to design something which only hits that one particular channel and only works on the tissues you want it to work in. It requires a lot of caution.
In the meantime, new pathways behind pain continue to emerge from studying CIP. One of the most exciting is a gene called PRDM12 which appears to work as a master switch, turning on and off a series of genes relating to pain neurons. But while the world of painkiller research is benefiting from the uniqueness of those with this extraordinary disorder, for CIP sufferers themselves, the prospect of a future life with pain and all its advantages remains slim.
Further study of CIP could yield painkillers that target only the genes that cause pain itself Credit: iStock. Pimstone points out that by taking part in studies, these individuals are seen by medical professionals, and in many cases for the first time, begin to receive specialist advice.
Through these studies, a diagnostic could also become available which can detect CIP early on. But Betz says he lives in hope. Perhaps one day they could use the understanding we gave them, to help us too. If you liked this story, sign up for the weekly bbc. The curse of the people who never feel pain.
Share using Email. Growing up, she burnt the skin off the palm of her hands on a pressure washer that her father had left running, and once ran around on a broken ankle for two whole days before her parents noticed the injury. She was once swarmed and bitten by hundreds of fire ants, has dipped her hands into boiling water, and injured herself in countless other ways, without ever feeling a thing. Ashlyn is one of a tiny number of people with congenital insensitivity to pain. The condition is so rare, in fact, that the doctor who diagnosed her in told her parents that she may be the only one in the world who has it.
Now, Woods and his colleagues have discovered yet more mutations that cause congenital insensitivity to pain. They studied 11 families form around the world, and identified within them individuals, all of whom suffer from either congenital pain insensitivity or hereditary sensory and autonomic neuropathy, another rare condition that also causes loss of pain sensation by damaging the nerves that carry pain signals up the spinal cord and then into the brain.
Using state-of-the-art DNA sequencing techniques, the researchers analysed and compared their genomes, and identified no less than 10 different mutations that cause congenital insensitivity to pain, all within a gene called PRDM12 , located on the long arm of chromosome 9.
Individuals carrying two defective copies of this gene produce a non-functional PRDM12 protein, and as a result of this have been unable to feel any kind of physical pain, or to distinguish between painfully hot and cold temperatures, from birth.
Most of them have experienced numerous, painless injuries. As chromatin plays a particularly significant role in the formation of nerve cells, the findings could explain why pain-sensing neurons do not form properly in patients suffering from congenital insensitivity to pain, they said. Babies who are born with CIP often damage themselves unintentionally by chewing their tongues, cheeks or hands.
In later life, sufferers have to take precautions against bruising and being burned by hot objects — although sufferers can often distinguish between warm and cold they do not feel the painful stimulus of heat.
A handful of genes have been implicated in contributing to the risk of inheriting the condition. By understanding the causes of the lack of sensitivity to pain in such patients, scientists hope to better understand the nature of pain and how to combat it in patients who suffer from long-term, chronic pain.
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