Congenital insensitivity to pain: Difference between revisions
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There are some cases where the condition is caused by increased production of [[endorphin]]s in the [[Human brain|brain]],{{Citation needed|date=August 2010}} in which case [[naloxone]] may be used as treatment. This treatment does not always work.<ref>{{cite journal | author = Manfredi M, Bini G, Cruccu G, Accornero N, Berardelli A, Medolago L | title = Congenital absence of pain | journal = Arch Neurol | volume = 38 | issue = 8 | pages = 507–11 | year = 1981 | pmid = 6166287 | doi=10.1001/archneur.1981.00510080069010}}</ref> |
There are some cases where the condition is caused by increased production of [[endorphin]]s in the [[Human brain|brain]],{{Citation needed|date=August 2010}} in which case [[naloxone]] may be used as treatment. This treatment does not always work.<ref>{{cite journal | author = Manfredi M, Bini G, Cruccu G, Accornero N, Berardelli A, Medolago L | title = Congenital absence of pain | journal = Arch Neurol | volume = 38 | issue = 8 | pages = 507–11 | year = 1981 | pmid = 6166287 | doi=10.1001/archneur.1981.00510080069010}}</ref> |
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In all cases, this disorder can be in the [[voltage-gated sodium channel]] [[SCN9A]] (Na<sub>v</sub>1.7). 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. Na<sub>v</sub>1.7 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 potential]]s in such neurons, it is expected that a loss of function mutation in SCN9A will lead to abolished nociceptive pain propagation.<ref name=Cox_2006>{{cite journal |author=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 |title=An SCN9A channelopathy causes congenital inability to experience pain |journal=Nature |volume=444 |issue=7121 |pages=894–8 |year=2006 |pmid=17167479 |doi=10.1038/nature05413}}</ref> |
In all cases, this disorder can be in the [[voltage-gated sodium channel]] [[SCN9A]] (Na<sub>v</sub>1.7). 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. Na<sub>v</sub>1.7 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 potential]]s in such neurons, it is expected that a loss of function mutation in SCN9A will lead to abolished nociceptive pain propagation.<ref name=Cox_2006>{{cite journal |author=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 |title=An SCN9A channelopathy causes congenital inability to experience pain |journal=Nature |volume=444 |issue=7121 |pages=894–8 |year=2006 |pmid=17167479 |doi=10.1038/nature05413}}</ref> |
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[[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).<ref>{{cite journal|last1=Chen|first1=YC|last2=Auer-Grumbach|first2=M|last3=Matsukawa|first3=S|last4=Zitzelsberger|first4=M|last5=Themistocleous|first5=AC|last6=Strom|first6=TM|last7=Samara|first7=C|last8=Moore|first8=AW|last9=Cho|first9=LT|last10=Young|first10=GT|last11=Weiss|first11=C|last12=Schabhüttl|first12=M|last13=Stucka|first13=R|last14=Schmid|first14=AB|last15=Parman|first15=Y|last16=Graul-Neumann|first16=L|last17=Heinritz|first17=W|last18=Passarge|first18=E|last19=Watson|first19=RM|last20=Hertz|first20=JM|last21=Moog|first21=U|last22=Baumgartner|first22=M|last23=Valente|first23=EM|last24=Pereira|first24=D|last25=Restrepo|first25=CM|last26=Katona|first26=I|last27=Dusl|first27=M|last28=Stendel|first28=C|last29=Wieland|first29=T|last30=Stafford|first30=F|last31=Reimann|first31=F|last32=von Au|first32=K|last33=Finke|first33=C|last34=Willems|first34=PJ|last35=Nahorski|first35=MS|last36=Shaikh|first36=SS|last37=Carvalho|first37=OP|last38=Nicholas|first38=AK|last39=Karbani|first39=G|last40=McAleer|first40=MA|last41=Cilio|first41=MR|last42=McHugh|first42=JC|last43=Murphy|first43=SM|last44=Irvine|first44=AD|last45=Jensen|first45=UB|last46=Windhager|first46=R|last47=Weis|first47=J|last48=Bergmann|first48=C|last49=Rautenstrauss|first49=B|last50=Baets|first50=J|last51=De Jonghe|first51=P|last52=Reilly|first52=MM|last53=Kropatsch|first53=R|last54=Kurth|first54=I|last55=Chrast|first55=R|last56=Michiue|first56=T|last57=Bennett|first57=DL|last58=Woods|first58=CG|last59=Senderek|first59=J|title=Transcriptional regulator PRDM12 is essential for human pain perception.|journal=Nature genetics|date=July 2015|volume=47|issue=7|pages=803-8|pmid=26005867|accessdate=31 July 2015}}</ref> <ref name="Uncomfortably numb: The people who feel no pain">{{cite web|last1=Costandi|first1=Mo|title=Uncomfortably numb: The people who feel no pain|url=http://www.theguardian.com/science/neurophilosophy/2015/may/25/the-people-who-feel-no-pain|website=the guardian|publisher=the guardian|accessdate=31 July 2015}}</ref> |
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Developmental disorders such as [[autism]] and related autistic-spectrum disorders such as [[pervasive developmental disorder]] and Asperger's Syndrome 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. |
Developmental disorders such as [[autism]] and related autistic-spectrum disorders such as [[pervasive developmental disorder]] and Asperger's Syndrome 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. |
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Revision as of 03:34, 31 July 2015
| Congenital insensitivity to pain | |
|---|---|
| Specialty | Neurology  |
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 etiology. Despite sounding beneficial, it is actually an extremely dangerous condition.
Presentation
For patients with this disorder, cognition and sensation are otherwise normal; for instance, patients can still feel discriminative touch (though not always temperature[1]), and there are no detectable physical abnormalities.
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. Unnoticed infections and corneal damage due to foreign objects in the eye are also seen. Because the child cannot feel pain, they may not respond to problems, thus being at a higher risk of more severe diseases.
Causes
There are some cases where the condition is caused by increased production of endorphins in the brain,[citation needed] in which case naloxone may be used as treatment. This treatment does not always work.[2] 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 will lead to abolished nociceptive pain propagation.[3]
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).[4] [5]
Developmental disorders such as autism and related autistic-spectrum disorders such as pervasive developmental disorder and Asperger's Syndrome 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.
Types of congenital pain indifference
There are generally two types of non-response exhibited.
- 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 will not flinch or withdraw when exposed to pain.[citation needed]
Incidence
It 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.[6]
Media depictions in fiction
In Stieg Larsson's Millennium series, former boxer Paolo Roberto discovers that Ronald Niedermann was born with congenital analgesia and is therefore, as he describes, "invulnerable" physically. ("He just keeps on going!") Even so, Roberto goes on to say that his inability to perceive pain is a severe danger because Niedermann has no way of understanding when his body is being put in mortal danger by way of punches, blows, burns, or even gunshots. It is suggested that human awareness of painful stimuli is an evolutionary necessity to avoid injury and death.
The Grey's Anatomy episode "Sometimes a Fantasy" features a young girl named Megan Clover who suffers from congenital analgesia, believing herself to be a superhero.
The House episode "Insensitive" features a young girl named Hannah Morganthal who has CIPA and attempts to fake pain to hide it.
The movie Bereavement features a boy named Martin Bristol who suffers congenital analgesia and who is kidnapped by a crazed man and taught the ways of murder.
One episode of N.C.I.S. featured a torturer who was "unable to feel pain himself" played by William Morgan Sheppard.
In season 1, episode 5 of the NBC show The Blacklist (TV Series) titled, "The Courier (No. 85)", the primary antagonist of the episode cannot feel pain and hides objects inside of his body.
In the 2011 slasher film Wrong Turn 4: Bloody Beginnings, the characters Three Finger, One Eye, and Saw Tooth are said to have the disorder by the head of the sanatorium they are in, in the portion of the film set in 1974, with it being theorized that the condition was caused by inbreeding. Due to their inability to properly register pain, the three were depicted as being prone to self-harm in their youth, mutilating, severing, and eating some of their own body parts. The disorder is also referenced throughout the series, especially the first film, Wrong Turn. The opening credits depict a medical journal talking about "resistance to pain" among other birth defects, and the entire series shows the antagonists ignoring non-crippling injuries.
In the play Almost, Maine by John Cariani, the vignette "This Hurts" is about a man with congenital analgesia, or "Hereditary Sensory Neuropathy Type 4", who is clocked in the head with an ironing board, and in the end feels the pain of love.
In the mystery novel The Freak Show Case by Brian D. Eyre and Lezlie K. King, the detective's client and prime suspect has congenital analgesia and believes he cannot feel pain. He learns quickly that not all pain is physical and that emotional pain can be extremely real and extremely motivating.[7]
The video game Dark Sector's protagonist, as shown in previews, has this disease and, as such, while others infected went mad from the pain, he remains sane and rational.
In an episode of Grimm titled "Game Ogre" (season 1, episode 8), an escaped murderer is believed to have this condition, but in reality, he is an ogre, whose race naturally doesn't feel pain.
Episode 31 of series 14 of Holby City sees fictional doctor Elliot Hope perform an operation on a patient with this disease.
In the fourth season episode of The X-Files titled "Home" the members of the Peacock family all exhibit insensitivity to pain. It is implied this is due to generations of inbreeding.
In an episode of Science Fiction Theater titled "The Strange People from Pecos", a little girl is shown as feeling no physical pain. For this and other reasons, she and her family are suspected of being aliens.
The protagonist of the The Corpse Reader by Antonio Garrido uses his condition to win bets when in trouble.
In DRAMAtical Murder, Noiz might have this condition, but his condition is depicted as a general inability to feel any sensation (except on his tongue) at all, rather than just pain.
In Rogue Legacy, if an heir with CIP is selected, the player will be unable to see his health bar.
Criminal Minds season 7 episode 4, "Painless"
Perception "Painless" 2014
Ticci-Toby, a fictional killer connected to the Slenderman Mythos, suffers from congenital analgesia and Tourette syndrome.
Otoha, the protagonist and title character of the anime Karas has the condition. It serves him well in his mortal life as a yakuza hit man. It is implied that he has the condition due to his father also being his brother (Otoha being the result of an incestuous relationship between his father/brother and their mother).
Nathan Wuornos, a character from the TV show Haven, has this disorder.
In episode nine of Welcome to Night Vale, it is mentioned that 53% of Night Vale's residents are "born without pain-sensing nerves."
See also
References
- ^ Online Mendelian Inheritance in Man (OMIM): Insensitivity to Pain, Congenital, with Anhidrosis; CIPA - 256800
- ^ 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.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ 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.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ 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. PMID 26005867.
{{cite journal}}:|access-date=requires|url=(help) - ^ Costandi, Mo. "Uncomfortably numb: The people who feel no pain". the guardian. the guardian. Retrieved 31 July 2015.
- ^ Minde J (2006). "Norrbottnian congenital insensitivity to pain". Acta orthopaedica. Supplementum. 77 (321): 2–32. PMID 16768023.
- ^ Eyre, Brian D. and King, Lezlie K. The Freak Show Case: A Pegasus Investigations Mystery. Swinging Cats and Blinking Hats Press, 2011, ISBN 978-0-615-51554-0.
External links
- 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.
- www.thefactsofpainlesspeople.com