Congenital insensitivity to pain (CIP), also known as congenital analgesia, is an inability for a person to feel physical pain due to various rare genetic conditions. CIP is caused by genetic mutations that affect the development or function of nociceptors, the sensory neurons responsible for recognizing tissue damage. Common symptoms include damage to the oral cavity, repeated bone fractures, and sometimes the inability to sweat. Some forms of CIP are also correlated with intellectual disabilities, learning disabilities, or attention deficit hyperactivity disorder (ADHD). Hereditary sensory autonomic neuropathies (HSAN) fall under the umbrella of CIP. Methods of treatment are still being explored. The epidemiology of CIP is unclear, given the relatively low number of reported cases.

Classification

The term congenital analgesia, also known as CIP, was first coined in the 1970s or 1980s. CIP is an umbrella term that describes a collection of rare genetic disorders that affect nerve tissue in either the peripheral or autonomic nervous systems. A 2019 paper argues that "congenital insensitivity to pain" is a misnomer, and theorizes that patients might still feel other (non-nociceptive) forms of pain, even if they are unable to accurately classify such sensations. Congenital insensitivity to pain with anhidrosis (CIPA) is a kind of CIP categorized by patients' inability to sweat (also known as HSAN-IV). The inability to regulate internal temperature can lead to unexplained persistent fevers. Children with this condition often sustain self-inflicted damage, both in and around the oral cavity (such as having bitten off the tip of their tongue) or fractures to bones. Many young children also present with persistent ear infections and damaged fingertips due to biting. Particular strains of CIP put individuals at a higher risk for developing Staphylococcus aureus infections. There are three mutations in SCN9A: W897X, located in the P-loop of domain 2; I767X, located in the S2 segment of domain 2; and S459X, located in the linker region between domains 1 and 2. This results in a truncated non-functional protein.

The PRDM12 gene is normally switched on during the development of pain-sensing nerve cells. People with homozygous mutations of the PRDM12 gene experience congenital insensitivity to pain (CIP).

Another gene implicated in human pain insensitivity is ZFHX2, which encodes zinc finger homeobox 2. A 2018 study analyzed six members of a family with inherited pain insensitivity and identified a "novel point mutation in ZFHX2, encoding a putative transcription factor expressed in small diameter sensory neurons" as the cause. This result revealed that opioid antagonists like naloxone and naltrexone may be effective in treating CIP in the future.

See also

References

  • "The Hazards of Growing Up Painlessly" by Justin Heckert, The New York Times Magazine, November 15, 2012. Profile of Ashlyn Blocker, 13, who has congenital insensitivity to pain.