Congenital insensitivity to pain
Rare genetic disorders causing lifelong inability to feel physical pain.
Congenital insensitivity to pain (CIP), also known as congenital analgesia, is a collection of rare genetic disorders that prevent a person from feeling physical pain. It results from mutations affecting nociceptors, the sensory neurons that detect tissue damage. The term 'congenital insensitivity to pain' was used in medical literature as early as the 1930s, and a 2019 paper suggested the alternative term 'congenital nociceptor deficiency' because patients might still feel other forms of pain. CIP is an umbrella term that includes hereditary sensory autonomic neuropathies (HSAN), with five types classified under a system originally proposed by Dyck in 1975 and later revised.
Quick Facts
- Specialty
- Neurology
- Symptoms
- Inability to perceive pain, self-inflicted damage to the oral cavity or fingertips, repeated bone fractures, persistent ear infections, corneal damage and infection, and sometimes inability to sweat
- Types
- HSANI, HSANII, HSANIII (familial dysautonomia), HSANIV (congenital insensitivity to pain with anhidrosis), and HSANV
- Causes
- Various genetic mutations
- Treatment
- Injury management and prevention
Facts from the source article.
Lore & Background
CIP is caused by mutations in genes such as SCN9A, PRDM12, ZFHX2, and NTRK1. The SCN9A gene encodes the Nav1.7 sodium channel, which is highly expressed in nociceptive neurons; loss-of-function mutations abolish pain signal propagation. Mutations in PRDM12 disrupt development of pain-sensing nerve cells. A 2018 study identified a mutation in ZFHX2 in the Marsili family of Italy, causing Marsili syndrome—a hyposensitivity rather than complete analgesia. Jo Cameron, a notable individual with CIP, has mutations in the FAAH gene and the pseudogene FAAH-OUT, leading to elevated endocannabinoid levels.
Reader's Guide
CIP is significant because it reveals the genetic and molecular basis of pain perception, offering potential targets for novel analgesics. The condition highlights the protective role of pain: without it, individuals suffer repeated fractures, oral self-injury, infections, and joint damage, leading to shortened life expectancy. The Marsili family and Jo Cameron provide unique insights into pain insensitivity. Treatment remains experimental; opioid antagonists like naloxone have temporarily restored pain sensation in one case. The epidemiology is unclear due to low case numbers, but a cluster in Vittangi, Sweden, suggests a founder effect. The condition underscores the complexity of nociception and the need for careful injury management.
Did You Know?
- A 2019 paper argued that 'congenital insensitivity to pain' is a misnomer and proposed 'congenital nociceptor deficiency' as an alternative.
- Marsili syndrome, caused by a ZFHX2 mutation, occurs in only one family in Italy and results in reduced pain sensitivity, not complete analgesia.
- Jo Cameron, who has congenital analgesia, carries mutations in the FAAH gene and the pseudogene FAAH-OUT, leading to high levels of the endocannabinoid anandamide.
- Nearly 40 cases of CIP have been reported in Vittangi, a village in northern Sweden.
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