Congenital insensitivity to pain

Congenital insensitivity to pain
Classification and external resources
OMIM 243000 147430
DiseasesDB 31214
MeSH D000699

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.[1] 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.[1] It is common for people with the condition to die in childhood due to injuries or illnesses going unnoticed.[1][2] Burn injuries are one of the more common injuries.[2]

Contents

Signs and symptomsEdit

A patient and doctor discuss congenital insensitivity to pain

For people with this disorder, cognition and sensation are otherwise normal; for instance, patients can still feel discriminative touch (though not always temperature[3]), and there are 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 suffer oral cavity damage both in and around the oral cavity (such as having bitten off the tip of their tongue) or fractures to bones.[2] Unnoticed infections and corneal damage due to foreign objects in the eye are also seen.[2][4]

There are generally two types of non-response exhibited:[1][4]

  • 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.

CausesEdit

It may be that the condition is caused by increased production of endorphins in the brain,[citation needed] in which case naloxone may be a treatment, but does not always work.[5] 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.[6]

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).[7][8]

Developmental disabilities such as autism can include varying degrees of pain insensitivity as a sign.[9] 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.

TreatmentEdit

The opioid antagonist naloxone was recently found to allow a woman with congenital insensitivity to pain to experience it for the first time.[10] Similar effects were observed in Nav1.7 null mice treated with naloxone.[10] As such, opioid antagonists like naloxone and naltrexone may be effective in treating the condition.[10]

EpidemiologyEdit

Congenital insensitivity to pain is found in Vittangi, a village in Kiruna Municipality in northern Sweden, where nearly 40 cases have been reported. A few Americans also have it.[11]

In popular cultureEdit

In the Millennium series by Swedish author Stieg Larsson, the character Ronald Niedermann is presented as suffering from the condition, rendering him an overtly stereotypical henchman, which includes precipitating several plot devices in the series.

The disorder has been portrayed in television shows and video games. In the season 3 episode of House M.D., "Insensitive", they treat a patient with the condition. In the Japanese anime and BL game, DRAMAtical Murder, a supporting character named, Noiz suffers from this disorder. When he was younger, his parents considered him a disgrace because he would play rough with other children because he didn't understand what pain felt like. The only pain he could feel was from his tongue. In season 3 of Perception U.S. TV series episode "Painless", there is a crime involving someone with the condition. In season 3 of Grey's Anatomy (U.S. TV series) episode "Sometimes a fantasy", Dr. Alex Karev was treating a young girl with this condition. In the 2008 video game Dark Sector, protagonist Hayden Tenno suffers from this condition. This becomes a plot point when he is infected by a virus that drives most people insane due to the severe pain it causes in victims, which he is unable to feel.

See alsoEdit

ReferencesEdit

  1. ^ a b c d Steven Linton (2005). Understanding Pain for Better Clinical Practice: A Psychological Perspective. Elsevier Health Sciences. p. 14. ISBN 0444515917. Retrieved April 13, 2017. 
  2. ^ a b c d Jennifer L. Hellier (2016). The Five Senses and Beyond: The Encyclopedia of Perception. ABC-CLIO. pp. 118–119. ISBN 1440834172. Retrieved April 13, 2017. 
  3. ^ Online Mendelian Inheritance in Man (OMIM) Insensitivity to Pain, Congenital, with Anhidrosis; CIPA -256800
  4. ^ a b Michael C. Brodsky (2016). Pediatric Neuro-Ophthalmology. Springer. p. 741. ISBN 1493933841. Retrieved April 13, 2017. 
  5. ^ Manfredi M, Bini G, Cruccu G, Accornero N, Berardelli A, Medolago L (1981). "Congenital absence of pain". Arch Neurol. 38 (8): 507–11. doi:10.1001/archneur.1981.00510080069010. PMID 6166287. 
  6. ^ Cox JJ, Reimann F, Nicholas AK, Thornton G, Roberts E, Springell K, Karbani G, Jafri H, Mannan J, Raashid Y, Al-Gazali L, Hamamy H, Valente EM, Gorman S, Williams R, McHale DP, Wood JN, Gribble FM, Woods CG (2006). "An SCN9A channelopathy causes congenital inability to experience pain". Nature. 444 (7121): 894–8. doi:10.1038/nature05413. PMID 17167479. 
  7. ^ Chen, YC; Auer-Grumbach, M; Matsukawa, S; Zitzelsberger, M; Themistocleous, AC; Strom, TM; Samara, C; Moore, AW; Cho, LT; Young, GT; Weiss, C; Schabhüttl, M; Stucka, R; Schmid, AB; Parman, Y; Graul-Neumann, L; Heinritz, W; Passarge, E; Watson, RM; Hertz, JM; Moog, U; Baumgartner, M; Valente, EM; Pereira, D; Restrepo, CM; Katona, I; Dusl, M; Stendel, C; Wieland, T; Stafford, F; Reimann, F; von Au, K; Finke, C; Willems, PJ; Nahorski, MS; Shaikh, SS; Carvalho, OP; Nicholas, AK; Karbani, G; McAleer, MA; Cilio, MR; McHugh, JC; Murphy, SM; Irvine, AD; Jensen, UB; Windhager, R; Weis, J; Bergmann, C; Rautenstrauss, B; Baets, J; De Jonghe, P; Reilly, MM; Kropatsch, R; Kurth, I; Chrast, R; Michiue, T; Bennett, DL; Woods, CG; Senderek, J (July 2015). "Transcriptional regulator PRDM12 is essential for human pain perception.". Nature Genetics. 47 (7): 803–8. doi:10.1038/ng.3308. PMID 26005867. 
  8. ^ Costandi, Mo. "Uncomfortably numb: The people who feel no pain". the guardian. the guardian. Retrieved 31 July 2015. 
  9. ^ Wolraich, Mark (2008). Developmental-behavioral Pediatrics: Evidence and Practice. Elsevier Health Sciences. p. 399. ISBN 9780323040259. 
  10. ^ a b c Minett, Michael S.; Pereira, Vanessa; Sikandar, Shafaq; Matsuyama, Ayako; Lolignier, Stéphane; Kanellopoulos, Alexandros H.; Mancini, Flavia; Iannetti, Gian D.; Bogdanov, Yury D.; Santana-Varela, Sonia; Millet, Queensta; Baskozos, Giorgios; MacAllister, Raymond; Cox, James J.; Zhao, Jing; Wood, John N. (2015). "Endogenous opioids contribute to insensitivity to pain in humans and mice lacking sodium channel Nav1.7". Nature Communications. 6: 8967. doi:10.1038/ncomms9967. ISSN 2041-1723. PMC 4686868 . PMID 26634308. 
  11. ^ Minde J (2006). "Norrbottnian congenital insensitivity to pain". Acta Orthopaedica Supplementum. 77 (321): 2–32. PMID 16768023. 

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