Congenital insensitivity to pain

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. The paper suggests "congenital nociceptor deficiency" as a possible alternative term. There are 5 types of HSAN that are classified as CIP disorders. As of 2025, the HSAN disorders are still classified using a system developed by Dyck P. J. in 1984. == Signs and symptoms ==

For people with this disorder, cognition and sensation are otherwise normal; for instance, patients can still feel discriminative touch (though not always temperature), and there are generally no detectable physical abnormalities. 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. These are also known as the HSAN disorders. • Nociceptors develop but do not respond to tissue signals, meaning that the patient can perceive the stimulus, but lacks an appropriate response. == Causes ==

CIP is caused by extremely rare genetic disorders. 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. ==Treatment==

As of 2020, there is no agreed-upon method in the medical community for treating CIP. This result revealed that opioid antagonists like naloxone and naltrexone may be effective in treating CIP in the future. Additionally, the genes that cause CIP provide promising targets for novel analgesics. == Epidemiology ==

A 2020 estimate places the incidence of CIP as one person in a million, based on the observation that under thirty cases are known in the United Kingdom. == See also ==