The disease behind the sleeper hit Mard Ko Dard Nahi Hota
Also known as congenital analgesia, congenital insensitivity to pain is a rare genetic disorder that inhibits the body to feel pain.
The 2019 Hindi film, Mard Ko Dard Nahi Hota, has in its centre a protagonist who shows no reaction to pain as he is afflicted with a rare medical condition called congenital insensitivity to pain (CIP). While the movie takes a comical turn and takes the audience through a series of adventures, the condition can lead to catastrophic situations in real life.
Also known as congenital analgesia, CIP is a rare genetic disorder that inhibits the body to feel pain. People with CIP have been documented putting their hands in boiling water, impaling themselves with rods, walking on hot coal and stepping on nails without registering any pain. They can, however, still tell the difference between hot and cold, dull and hard, and perceive changes in pressure.
The inability to sense pain comes with a host of issues: young children chew off their tongues when they start teething, fractures are common, joints become arthritic and there is a high likelihood of burn injuries. This is because the body modulates its movements and mannerisms in response to pain, and without the feedback mechanism the body can’t understand the strain it is putting itself through.
Those suffering from CIP are likely to be wheelchair-bound and there is a high risk of suicide as well. Internal injuries are also a worry - Steven Pete, a person afflicted with CIP, told the BBC that he is most concerned about things like appendicitis and every time he has stomach issues or a fever, he goes straight to the doctor.
It is an incredibly rare dysfunction; only 20 cases are mentioned in the literature but researchers assume that there more undocumented cases out there. It is considered a form of peripheral neuropathy since it affects the peripheral nervous system. Cells involved with sensing touch, smell and pain are unable to transmit messages across to the brain. A large number of those with CIP also have no sense of smell (anosmia).
What causes CIP?
The gene SCN9A has been linked to congenital insensitivity to pain. It provides the instructions for building a part of a sodium channel called NAV1.7. The sodium channels transmit pain signals to the spinal cord and brain. The genetic mutation of SCN9A renders these sodium channels ineffective in transmitting signals, thus the ability to feel pain. A similar pathway influences smell, which explains why those with CIP also have anosmia.
The PRDM12 gene, which plays a key role in formulating chromatin, also appears in a mutated form in those with CIP. A study showed that the mutation in 11 unrelated families with CIP blocked off the gene. Chromatin plays a major role in the formation of nerve cells, so this may explain the symptoms of the disorder.
Living with CIP
Gene therapy is not yet advanced enough to reverse the effects of the mutations in those afflicted with CIP. Symptom management is the treatment available at the moment. But with increasing awareness, various institutes are working with CIP families to formulate solutions and come to a deeper understanding of pain.
A new frontier in pain management
Following the breakthrough with SCN9A, pharmacological companies across the world have been in a race to develop a new generation of drugs dealing with chronic pain. Opioids are used to combat debilitating pain, but the opioid crisis and side effects associated with them have raised alarm bells.
Studies are underway to target NAV1.7 channels but it will be a while before they come to the market. The mechanisms involved are convoluted and affect various parts of the body. The hope is that this rare disease will help us overcome the pain of various kinds and lead better lives. The newfound impetus in research should also offer a ray of light for those suffering from CIP.
For more on this topic, please read our article on Peripheral Neuropathy.
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