1. No Pain No Gain: Congenital Insensitivity
to Pain and Anhidrosis
Lynna Nguyen | Survey Center | SORCE U-Prep | November 20, 2014
Introduction
While enduring waves of extreme pain or
constant pain it is easy to forget how
important pain is as a diagnostic tool.
Experiencing no pain is the obvious desire
of those suffering any agony. However,
what is the price that must be paid when the
body’s most basic distress signal is shut off?
Congenital insensitivity to pain with
anhidrosis (CIPA) is a rare autosomal
recessive disorder that causes those affected
to not feel pain [1].
Affecting 1 in every 125 million people,
CIPA is rare but those living with the
condition suffer from the inability to sweat,
the inability to feel extreme temperatures,
and show cognitive impairment alongside
the consequences of feeling no pain. The
average lifespan of someone diagnosed with
CIPA is 25 years old [1,2].
CIPA is caused by a mutation in the NTRK1
gene. Tropomyosin-related kinase A, the
product of NTRK1, functions as the receptor
of nerve growth factor. Normal nerve
growth factor-tropomysin-related kinase A
signal transduction is essential for the
survival and maintenance of primary
afferent neurons [2]. Without proper
development and differentiation of these
neurons, complete neuropathy of the
autonomic nervous system occurs [3].
The following report will consist of an in
depth look at various case studies to
hopefully showcase the severity of this
condition and what a life without pain
entails.
Reported Case Descriptions
The first four patients are pediatric patients
from Iran seen at Iman Khomeini hospital
(fig. 1). Only one patient needed
amputation, but later returned with severe
cellulitis from the amputation. The other
three were given antibiotics to treat their
osteomyelitis. However, treatment of the
self-mutilation was also necessary with 3 out
of the 4 patients showing osteolysis in their
dental and facial structures.
However not all cases of CIPA come from
consanguineous parents. A few exceptions
exist. The next case surrounds a 10-year-old
boy born to nonconsanguineous parents of
Turkish descent. He was admitted to
Maasstad Hospital Burn Center in
Rotterdam, The Netherlands after he and his
parents noticed severe blisters on his
buttocks. He had been sitting on a central
heating system for hours playing video
games and did not sense any pain or heat.
Upon further examination doctors found he
also had several scars on his lips and tongue,
possibly from biting and drinking hot
beverages without detecting heat [4].
Treatment Options
Treating CIPA entails treating the symptoms
of a life without pain. There is no way to
repair extreme neuropathy of the autonomic
nervous system, therefore the only way to
treat CIPA is to treat the superficial and
deep wounds that manifest when the body
has no way of signaling for aid.

2. Patient 1 Patient 2 Patient 3 Patient 4
Age, Sex 12 year old boy 13 year old girl 8 year old girl 7 year old girl
Osteomyelitis Chronic Chronic Chronic
Chronic with
gangrene
Mental
Retardation
Yes Yes Yes No
Self-mutilation Mostly fingertips No
Hands and
fingers
Inconclusive
Immune tests,
viral markers
Normal Normal Normal Normal
Fig.1: The four pediatric patients of Iran treated at Iman Khomeini Hospital. All four patients are children of first
cousins.
Infections are treated with antibiotics.
Deeper tissue and bone infections are treated
with surgery to remove necrotic tissue
followed by antibiotics to clear away any
remaining infection. If the previous two
methods show no sign of improvement
amputation is the next option [1].
For the most part death among CIPA
patients are due conditions that are treatable,
such as heat attack, but go undetected due to
the insensitivity to heat [1]. Without routine
visits to the doctor unnecessary deaths will
continue to occur.
Conclusions
From the information in the case studies it is
clear that deep bone and tissue infections are
the most common side effect of CIPA that
cause patients to seek care. When in the
hospital’s care it apparent that self-
mutilation is also a common side effect of
CIPA, often coupled with mental
retardation, which increases the risk and
severity of the self-mutilation.
Furthermore, physiological tests are found to
be ineffective when attempting to diagnose
CIPA due to immune tests and viral markers
being normal or negative for pathogens. Due
to these conclusions it is important to note
that diagnosis of CIPA requires physician
awareness and familiarity with the signs of
CIPA. Without the knowledge, inaccurate
assessments of child abuse or other ailments
endanger the patients life as they spend
more time thinking their experiences are
normal instead of knowing they need to, or
have someone help to, routinely check for
damage to the body: cuts, scratches,
discoloration of the skin, etc. Awareness is
key.
Future Development
There is still very much to be discovered and
learned about CIPA. The lack of knowledge
may be due to the fact that it is a very
preventable condition. Those affected by
this ailment are mostly progeny of
consanguineous parents, thus regions where
inbreeding is not common practice do not
have many reported cases of CIPA. Simply
being preventable makes research on CIPA
low priority. On the other hand, scientific
progress is not always about finding cures,
eradicating illness, and technological
innovation. Progress can be interpreted
many ways depending on point of view.
1. From a diagnostic stance,educating
physicians and increasing awareness of
the condition will decrease the number
of misdiagnoses of child abuse.

3. Misdiagnoses prolong the time between
the initial physician encounter and
devising a step-by-step regimen
implemented to manage CIPA.
2. From a researchers’ viewpoint, the
inability to feelpain is a novel and
exciting condition to be revealed. With
further research to fully understand
CIPA,maybe there can be hope of a
new form of pain management. If there
was a way to temporarily knockout
NTRK1 and cause patients to
temporarily feel no pain during
recovery, it would decrease dependency
on narcotics and analgesics for pain
management and allow patients to
return to normal every day function
sooner without the drawbacks of
current pain medication. However,the
inherent drawback with this hope is that
CIPA is congenital, meaning it is
present at birth, therefore knocking out
NTRK1 after birth may have no affect
since this gene is mostly active in
development of neurons. Although, it is
possible that with increased knowledge
of this condition may lead to discovery
of a different gene or process that
regulates neuron signaling that may be
tampered with to temporarily relieve
the burden of pain.
No matter what the future may or may not
bring, it is crucial to note that pain plays a
significant role in diagnostics and
maintenance of over all health. While it is
tempting to want to live a life without pain,
there are more drawbacks than benefits with
this life. Pain provokes the body and signals
when urgent care is necessary, possibly life-
saving care. There is no way to diagnose
internal damage or seek care for internal
damage without pain as an indicator. It goes
to show that with no pain comes no gains
towards maintaining a healthy body and
having a normal quality of life.
Acknowledgements
I would like to thank Leon Chan and Megan
Miller for being so understanding and
flexible with the setbacks that occurred
during the development of this project.
However few, I would like to thank the
researchers that made it possible for me to
create a homogenous superficial
understanding of a wild condition that seems
too extreme to be true. Very few articles on
PubMed and Google in general came up so
the appreciation for the literature on CIPA is
that much greater. But most of all I would
like to thank the patients I have the pleasure
of speaking to every day at the Survey
Center for inspiring me to look into possible
remedies for pain and researching what life
would be like for them if they were granted
their wishes to live on the opposite end of
the pain spectrum and truly feel no pain.
References
[1] Daneshjou K, Jafarieh H, Raaeskarami
SR. Congenital Insensitivity to Pain and
Anhydrosis (CIPA) Syndrome; A Report of
4 Cases. Iran J Pediatr. 2012 Sep;22(3):412-
6. PMID: 23400697.
[2] Liu S, Wu N, Liu J, Ming X, Chen J,
Pavelec D, Su X, Qiu G, Tian Y, Giampietro
P, Wu Z. Novel NTRK1 Frameshift
Mutation in Congenital Insensitivity to Pain
With Anhidrosis. J Child Neurol. 2014 Oct
14. PMID: 25316729.
[3] Sasnur AH, Sasnur PA, Ghaus-Ul RS.
Congenital insensitivity to pain and
anhidrosis. Indian J Orthop. 2011
May;45(3):269-71. doi: 10.4103/0019-
5413.80047. PMID: 21559108.
[4] van den Bosch GE, Baartmans MG, Vos
P, Dokter J, White T, Tibboel D. Pain
insensitivity syndrome misinterpreted as
inflicted burns. Pediatrics. 2014

4. May;133(5):e1381-7. doi:
10.1542/peds.2013-2015. Epub 2014 Apr
14. PMID: 24733875.