Congenital insensitivity to pain
Congenital insensitivity to pain (CIP), also known as congenital analgesia, is one or more rare conditions in which a person cannot feel (and has never felt) physical pain. The conditions described here are separate from the HSAN group of disorders, which have more specific signs and cause. Because feeling physical pain is vital for survival, CIP is an extremely dangerous condition. It is common for people with the condition to die in childhood due to injuries or illnesses going unnoticed. Burn injuries are among the more common injuries.
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.
Because children with the disorder cannot feel pain, they may not respond to problems, thus being at a higher risk of more severe diseases. Children with this condition often sustain oral cavity damage both in and around the oral cavity (such as having bitten off the tip of their tongue) or fractures to bones. Unnoticed infections and corneal damage due to foreign objects in the eye are also seen.
- Insensitivity to pain means that the painful stimulus is not even perceived: a patient cannot describe the intensity or type of pain.
- Indifference to pain means that the patient can perceive the stimulus, but lacks an appropriate response: they do not flinch or withdraw when exposed to pain.
It may be that the condition is caused by increased production of endorphins in the brain. In this case, naloxone may be a treatment, but it does not always work. In all cases, this disorder can be in the voltage-gated sodium channel SCN9A (Nav1.7). Patients with such mutations are congenitally insensitive to pain and lack other neuropathies. 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. Nav1.7 channels are expressed at high levels in nociceptive neurons of the dorsal root ganglia. As these channels are likely involved in the formation and propagation of action potentials in such neurons, it is expected that a loss of function mutation in SCN9A leads to abolished nociceptive pain propagation.
Homozygous microdeletion in the FAAH-OUT pseudogene of the fatty acid amide hydrolase chromosomal region that is expressed in the brain and dorsal root ganglia was identified as the cause of congenital analgesia in a single individual (as of 2019). The individual experienced lifelong insensitivity to pain and was oblivious to cuts and burns, did not experience pain during childbirth, did not experience pain from degeneration of a hip that required hip replacement surgery, and did not require analgesics for postoperative pain. Furthermore, the individual exhibited expedited wound healing and reduced scarring, could not sense heat from chili peppers, did not experience depression, fear, and anxiety and lacked a normal fear response to erratic and aggressive behaviour. However, the individual also experienced slight memory impairment (was prone to losing the trail of thought while speaking, and experienced some forgetfulness), and could not experience thrill ("adrenaline rush").
Developmental disabilities such as autism can include varying degrees of pain insensitivity as a sign. However, since these disorders are characterized by dysfunction of the sensory system in general, this specific condition is not in itself an indicator of any of these conditions.
The opioid antagonist naloxone allowed a woman with congenital insensitivity to pain to experience it for the first time. Similar effects were observed in Nav1.7 null mice treated with naloxone. As such, opioid antagonists like naloxone and naltrexone may be effective in treating the condition.
- Hereditary sensory and autonomic neuropathy
- Pain asymbolia
- Linton S (2005). Understanding Pain for Better Clinical Practice: A Psychological Perspective. Elsevier Health Sciences. p. 14. ISBN 978-0444515919. Retrieved April 13, 2017.
- Hellier JL (2016). The Five Senses and Beyond: The Encyclopedia of Perception. ABC-CLIO. pp. 118–119. ISBN 978-1440834172. Retrieved April 13, 2017.
- Online Mendelian Inheritance in Man (OMIM) Insensitivity to Pain, Congenital, with Anhidrosis; CIPA -256800
- Brodsky MC (2016). Pediatric Neuro-Ophthalmology. Springer. p. 741. ISBN 978-1493933846. Retrieved April 13, 2017.
- Manfredi M, Bini G, Cruccu G, Accornero N, Berardelli A, Medolago L (August 1981). "Congenital absence of pain". Archives of Neurology. 38 (8): 507–11. doi:10.1001/archneur.1981.00510080069010. PMID 6166287.
- Bennett DL, Clark AJ, Huang J, Waxman SG, Dib-Hajj SD (April 2019). "The Role of Voltage-Gated Sodium Channels in Pain Signaling". Physiological Reviews. 99 (2): 1079–1151. doi:10.1152/physrev.00052.2017. PMID 30672368.
- Cox JJ, Reimann F, Nicholas AK, Thornton G, Roberts E, Springell K, et al. (December 2006). "An SCN9A channelopathy causes congenital inability to experience pain". Nature. 444 (7121): 894–8. Bibcode:2006Natur.444..894C. doi:10.1038/nature05413. PMID 17167479.
- McDermott LA, Weir GA, Themistocleous AC, Segerdahl AR, Blesneac I, Baskozos G, Clark AJ, Millar V, Peck LJ, Ebner D, Tracey I, Serra J, Bennett DL (March 2019). "V1.7 in Human Nociception". Neuron. 101 (5): 905–919.e8. doi:10.1016/j.neuron.2019.01.047. PMC 6424805. PMID 30795902.
- Chen YC, Auer-Grumbach M, Matsukawa S, Zitzelsberger M, Themistocleous AC, Strom TM, et al. (July 2015). "Transcriptional regulator PRDM12 is essential for human pain perception". Nature Genetics. 47 (7): 803–8. doi:10.1038/ng.3308. PMID 26005867.
- Costandi M (2015-05-25). "Uncomfortably numb: The people who feel no pain". the guardian. the guardian. Retrieved 31 July 2015.
- Murphy H (2019-03-28). "At 71, She's Never Felt Pain or Anxiety. Now Scientists Know Why". The New York Times. ISSN 0362-4331. Retrieved 2019-03-30.
- Habib AM, Okorokov AL, Hill MN, Bras JT, Lee MC, Li S, Gossage SJ, van Drimmelen M, Morena M, Houlden H, Ramirez JD, Bennett DL, Srivastava D, Cox JJ (March 2019). "Microdeletion in a FAAH pseudogene identified in a patient with high anandamide concentrationsand pain insensitivity". British Journal of Anaesthesia. doi:10.1016/j.bja.2019.02.019. PMID 30929760.
- Wolraich M (2008). Developmental-behavioral Pediatrics: Evidence and Practice. Elsevier Health Sciences. p. 399. ISBN 9780323040259.
- Minett MS, Pereira V, Sikandar S, Matsuyama A, Lolignier S, Kanellopoulos AH, Mancini F, Iannetti GD, Bogdanov YD, Santana-Varela S, Millet Q, Baskozos G, MacAllister R, Cox JJ, Zhao J, Wood JN (December 2015). "Endogenous opioids contribute to insensitivity to pain in humans and mice lacking sodium channel Nav1.7". Nature Communications. 6 (1): 8967. doi:10.1038/ncomms9967. PMC 4686868. PMID 26634308.
- Minde JK (April 2006). "Norrbottnian congenital insensitivity to pain". Acta Orthopaedica. Supplementum. 77 (321): 2–32. PMID 16768023.
- The Hazards of Growing Up Painlessly By JUSTIN HECKERT, New York Times, November 15, 2012. Profile of Ashlyn Blocker, 13, who has congenital insensitivity to pain.