written by: bjlbyron•edited by: lrohner•updated: 10/24/2010
Can you imagine what it is like to not be able to feel any pain whatsoever? Those who are inflicted with congenital pain insensitivity can, as they do not experience pain at all. Read on to learn about this unusual condition and what is known about its underlying genetic cause.
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What Is Congenital Pain Insensitivity?
Congenital pain insensitivity (CPI) is also commonly referred to as congenital pain insensitivity with anhidrosis, is an autosomal recessive genetic disorder that is characterized by anhidrosis (lack of the ability to produce sweat), recurring fever, self-multilating behavior, mental defects and the inability to sense noxious stimuli. Examples of noxious stimuli include pinching of the skin, burning of the skin and exposure of the skin to a harmful irritant such as bleach.
Although recurring fever, mental defects and self-multilating behavior are clearly undesirable symptoms, the inability to sweat or experience noxious stimuli may seem advantageous to some. However, this is simply not the case. Those who cannot sweat have trouble keeping their body cool, which explains the tendency of those who are affected by CPI to suffer recurring fever symptoms. Further, the inability to experience pain is problematic because pain alerts the brain that the body is suffering from an insult or injury that needs to be remedied, such as removing one's hand from a hot iron or having a broken bone treated, for example. People who cannot feel pain are prone to suffering a bodily injury or making one worse.
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What Is The Underlying Genetic Cause Of Congenital Pain Insensitivity?
In the 1990s, a multi-national team of molecular geneticists discovered mutations in the gene known as NTRK1, also commonly referred to as TRKA, and proved that mutations in the NTRK1 gene are what causes CPI. The NTRK1 gene has been shown to encode the protein neurotrophic tyrosine kinase receptor type I. A normal, mutation-free copy of the NTRK1 gene encodes a normal copy of neurotrophic tyrosine kinase receptor type I, whereas mutant copies of the NTRK1 gene encode either no or defective copies of the neurotrophic tyrosine kinase receptor type I protein.
In healthy individuals, neurotrophic tyrosine kinase receptor type I helps support the survival of sympathetic ganglion neurons and nociceptive sensory neurons in dorsal root ganglia. Functioning sympathetic ganglion neurons are needed for, among other things, stimulating sweat glands to produce sweat, whereas nociceptive sensory neurons are involved in the sensing of noxious stimuli, such as those described above. Those who have two defective copies of the NTRK1 gene cannot synthesize functional neurotrophic tyrosine kinase receptor type I protein. Their sympathetic ganglion neurons and nociceptive sensory neurons in dorsal root ganglia therefore are prone to dying, which explains why they experience the symptoms that are described above.
There is no known cure for CPI. Typically, some symptoms, such as recurring fever and inability to sweat, for example, can be directly treated, but others, such as inability to sense noxious stimuli, for example, are not currently treatable. It is hoped, however, that better treatments courses will be developed as more is learned about CPI and the NTRK1 gene.
K. Huehne et al., Novel missense, insertion and deletion mutations in the neurotrophic tyrosine kinase receptor 1 type gene (NTRK1) associated with congenital insensitivity to pain and anhidrosis, Neuromuscular Disorders 18:159-166 (2008).
S. Mardy et al., Congenital Insensitivity to Pain with Anhidrosis: Novel Mutations in the TRKA (NTRK1) Gene Encoding A High-Affinity Receptor for Nerve Growth Factor, American Journal of Human Genetics 64:1570-1579 (1999). http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1377900/pdf/10330344.pdf