Congenital pain insensitivity (CPI) is an autosomal recessive disorder characterized by the inability to discern physical pain although the ability to feel a stimulus is intact [1]. This rare ailment is considered to be a part of the hereditary sensory and autonomic neuropathies (HSAN) [2]. CPI is a genetically heterogeneous disease caused by mutations in the SCN9A [3], NTRK1 [4], and NGFB genes [5]. If left undetected and unaddressed, this condition can affect the patient's overall health and result in serious outcomes.

The clinical presentation reflects which gene is affected. Generally, the cases demonstrate a lack of pain perception with burns, bone fractures, joint dislocations, and other injuries [6]. Moreover, they engage in self-mutilation by biting on their tongue, lips, and digits [7] [8] resulting in laceration and ulceration of oral mucosa and scarring of the cheeks [9] [10]. Additionally, affected individuals may exhibit mental retardation and developmental delays with varying degrees. Also common are behavioral issues and emotional lability. Furthermore, patients may be prone to developing neurotrophic keratitis, corneal ulcerations and scarring, and even infection.

Depending on the mutated gene and the resultant clinical phenotype, anosmia [2] or anhidrosis [4] [10] are prominent features. The latter predisposes to recurrent febrile episodes [10].

Complications

Painless injuries induce severe consequences such as recurrent disease and repeated fractures. Specifically, sufferers are susceptible to developing osteomyelitis, acroosteolysis, and Charcot joints. Additionally, they may develop oral ulcers and other lesions, which further lead to infections, oral bleeding, and malnutrition [10]. If not treated, poor outcomes such as failure to thrive are likely [10].

Physical exam

The neurologic exam in subjects with CPI reveals normal touch, vibration, and position senses. Remarkable overall findings include joint deformities, disfiguring injuries, oral and eye abnormalities.

• Crying

  When Isaac was small, he stuck his whole hand into his mother’s mug of hot coffee and didn’t cry. Then he put his hand on a hot stove burner and received third-degree burns and still did not cry. [nytimes.com]

  If she takes a hard fall, Ashlyn won’t cry. Ashlyn is among a tiny number of people in the world known to have congenital insensitivity to pain with anhidrosis, or CIPA — a rare genetic disorder that makes her unable to feel pain. [nbcnews.com]

  Although absence of tears (alacrima) with emotional crying is one of the cardinal features of the disorder, this sign may not be immediately recognized since lack of overflow tears is normal until about seven months of age. [ojrd.biomedcentral.com]

• Limb Pain

  HOWEVER, the counterargument to this might be people who are born without a limb but report phantom limb pain. For these people, however, they have learnt pain through intact nociceptive capacity elsewhere, so it is a bit different. [bodyinmind.org]

  Phantom limb pain (Flor 2002). F. Brachial plexus avulsion (Wynn Parry 1980). G. Central post-stroke pain (Bowsher 1996; Gonzales and Casey 2003). H. [shiga-med.ac.jp]

• Camping

  Which is how Camp Painless But Hopeful got started. Tara called a place called Camp Twin Lakes in Winder, Ga., four hours from Patterson, and asked about holding a weekend retreat there for kids who feel no pain. The staff agreed. [nytimes.com]

• Vomiting

  It is present at birth and symptoms include floppiness, severe feeding difficulties (vomiting, constipation), pneumonia (that occurs because of an inability to swallow and cough), lack of taste, inability to produce tears, unstable temperature and blood [contact.org.uk]

  These cause feeding difficulties, vomiting and recurrent aspiration pneumonia leading to chronic lung disease. [indianjpain.org]

  Thus laryngeal mask may induce vomiting and reduce the efficiency of vaccum suction in oropharyngeal. That is probably why LMA have high risk of aspiration for CIPA patients. [omicsonline.org]

  These sorrel formulations may cause nausea or vomiting when taken with the prescription drugs metronidazole (Flagyl®) or disulfiram (Antabuse®). Avoid if pregnant or breastfeeding. [livingnaturally.com]

  Gastrointestinal dysmotility is infrequent; vomiting is not a feature of the disease and cyclical crises do not occur [ 1, 3 ]. Insensitivity to hypoxia and hypercapnia has not been noted. [ojrd.biomedcentral.com]

• Nausea

  Thus the concept has been proposed that the crisis may represent a type of autonomic seizure and that nausea may be the aura [ 52 ]. [ojrd.biomedcentral.com]

  These sorrel formulations may cause nausea or vomiting when taken with the prescription drugs metronidazole (Flagyl®) or disulfiram (Antabuse®). Avoid if pregnant or breastfeeding. [livingnaturally.com]

• Dental Caries

  Recommended Surveillance for Individuals Congenital Insensitivity to Pain Manifestation Evaluation Frequency/Comment Dental caries/tooth damage Dental care Regular examinations (at least every 6 months) Early injuries Evaluation by parents & caregivers [ncbi.nlm.nih.gov]

  Recurrent fever may lead to xerostomia and increased incidence of dental caries, oral infections such as candidiasis. [indianjpain.org]

• Hypersalivation

  There is a generalized increase in secretions resulting in excessive diaphoresis, gastrorrhea, bronchorrhea and hypersalivation with copious drooling. [ojrd.biomedcentral.com]

• Alopecia

  The patient did not have the manifestations of alopecia and visual disturbances. Physical examination didn’t display muscle hypotonia and power decline. Basic laboratory testing was normal. This child had no history of surgery or other fractures. [omicsonline.org]

• Neuropathic Arthropathy

  Repeated trauma to joints results in progressive inflammation, damage, and deformity of the affected joints (Charcot joint or neuropathic arthropathy). The large, weight-bearing joints are especially prone to this complication. [rarediseases.org]

• Self-Mutilation

  Moreover, they engage in self-mutilation by biting on their tongue, lips, and digits resulting in laceration and ulceration of oral mucosa and scarring of the cheeks. [symptoma.com]

  Close attention of children with CIPA is necessary to prevent injuries, burns, fractures, corneal ulceration, and self-mutilation. [e-ijd.org]

  Self-mutilating behavior due to a lack of pain perception is frequently seen in these patients using their teeth. [1] No specific therapy is available. [pediatricneurosciences.com]

  Self-mutilation, typically manifesting as biting of the lips and tongue, has also been observed in these patients. [indianjpain.org]

• Self-Mutilation

  Moreover, they engage in self-mutilation by biting on their tongue, lips, and digits resulting in laceration and ulceration of oral mucosa and scarring of the cheeks. [symptoma.com]

  Close attention of children with CIPA is necessary to prevent injuries, burns, fractures, corneal ulceration, and self-mutilation. [e-ijd.org]

  Self-mutilating behavior due to a lack of pain perception is frequently seen in these patients using their teeth. [1] No specific therapy is available. [pediatricneurosciences.com]

  Self-mutilation, typically manifesting as biting of the lips and tongue, has also been observed in these patients. [indianjpain.org]

• Indifference to Pain

  Other names for congenital insensitivity to pain include: asymbolia for pain channelopathy-associated insensitivity to pain CIP congenital analgesia congenital insensitivity to pain congenital pain indifference indifference to pain, congenital, autosomal [thinkgenetic.com]

  […] analgesia congenital indifference to pain congenital pain indifference indifference to pain, congenital, autosomal recessive pain insensitivity, congenital Dabby R. [ghr.nlm.nih.gov]

  A syndrome characterized by indifference to PAIN despite the ability to distinguish noxious from nonnoxious stimuli. Absent corneal reflexes and INTELLECTUAL DISABILITY may be associated. [connects.catalyst.harvard.edu]

  There is indifference to pain, but this is usually far less of a problem than the autonomic dysfunction. Intelligence is usually normal, but emotions can be unstable. [contact.org.uk]

  In those with congenital indifference to pain, though, painful stimuli are perceived; but there is an absence of the affective response to pain, rather than a lack of signal transmission. [indianjpain.org]

• Stroke

  Central post-stroke pain (Bowsher 1996; Gonzales and Casey 2003). H. [shiga-med.ac.jp]

  Use cautiously with asthma or a history of ulcers or stroke. Avoid if pregnant. Children should not take doses larger than what is commonly found in foods. [livingnaturally.com]

Infants and young children with an impaired response to pain and repeated harmful behaviors should be evaluated for this medical entity. The workup will include the patient's history and presentation, a complete physical exam (including a focus on neurologic, oral, and eye tests), and specialized studies.

Diagnostic tests

Biopsy of the skin and nerves can confirm the diagnosis by revealing distinctive findings [11]. Specifically, microscopic analysis of the skin may show the abnormal functioning of nerves innervating eccrine sweat glands while examination of the nerve tissue may demonstrate a diminished quantity of unmyelinated small-diameter fibers. Another exam is characterized by applying pressure with a pen onto the patient's nail bed. Note that an absent withdrawal response is a result of the lack of pain perception [11]. Clinicians may perform the axonal flare test, in which an intradermal histamine injection results in a characteristic skin response. An electromyogram (EMG) will typically yield normal results [1]. Genetic testing is not routinely done since there are many mutations associated with CPI.

Treatment depends on the patient's age and intelligence, as well as the parent's attitude and cooperation. [pediatricneurosciences.com]

[…] and prognosis No specific treatment is available for CIP 1,7. [radiopaedia.org]

Treatment Self treatment : Most simple boils can be treated at home. Ideally, the treatment should begin as soon as a boil is noticed. Early treatment may prevent later complications. [livingnaturally.com]

[…] guard [ Hutton & McKaig 2010 ] Bone fractures Standard treatment Treatment w/an external fixator may lead to potentially serious infectious complications. [ncbi.nlm.nih.gov]

HSAN is described additionally to be a genetic disorder created through mutations with no cure or treatment. Although there is therapy to deal with the symptoms, it does not deal with the disorder, and there is no definitive treatment to each child. [neurosciencefundamentals.unsw.wikispaces.net]

[…] reported the following features 9 : acro-osteolysis within the first year of life (100%) limb fractures with prominent periosteal reaction and exuberant callus (100%) osteomyelitis (50%) brain volume loss with mild ventriculomegaly (50%) Treatment and prognosis [radiopaedia.org]

The prognosis for independent function depends on the degree of disease expression and the ability to control the secondary clinical problems. Prognosis and goals There are a number of hereditary and sensory and autonomic neuropathies (HSAN). [ojrd.biomedcentral.com]

The etiology and pathogenesis of CIP depends on the specific type of HSAN. For example: HSAN2D (channelopathy-associated congenital insensitivity to pain) : patients have homozygous mutations in the SCN9A gene 4,7. [radiopaedia.org]

Common syndromes with unknown etiology (e.g., intercostal neuralgia). B. Painful polyneuropathies (including acute-onset and slow-onset distal symmetrical polyneuropathies) HIV (Schiffito et al. 2002; Luciano et al. 2003). [shiga-med.ac.jp]

[…] insensitivity to pain to experience it for the first time. [14] Similar effects were observed in Na v 1.7 null mice treated with naloxone. [14] As such, opioid antagonists like naloxone and naltrexone may be effective in treating the condition. [14] Epidemiology [en.wikipedia.org]

Epidemiology HSAN IV is extremely rare among most populations with the exception of the Japanese and Israeli-Bedouins. The prevalence is unknown, but it was seen the disorder is more diffused in cultures in which intermarriage is accepted. [flipper.diff.org]

Despite the discovery of these two channels and their modes of action, the pathophysiology of pain perception is incompletely understood. To date, mutations in Nav1.7 (OMIM 603415) have been implicated in three pain-related syndromes in humans. [karger.com]

Endorphins are molecules in your body that when released, prevent nerve cells from releasing more pain signals. [thetartan.org]

Tea tree oil : Tea tree oil is purported to have antiseptic properties, and has been used traditionally to prevent and treat infections. [livingnaturally.com]

In certain extreme cases, the child's baby teeth are extracted to prevent self mutilation of tongue, lips and fingers until they grow their adult teeth. Figure 4. [neurosciencefundamentals.unsw.wikispaces.net]

Common practices can be: • prevention of self-mutilation by smoothing or extracting teeth; • prevention of debilitating orthopedic problems by daily evaluation for early signs of unrecognized injury; • prevention of neurotrophic keratitis with tarsorrhaphy [flipper.diff.org]

The parents need to be educated about simple measures like avoiding excessive wrapping, preventing dehydration, and measures to reduce hyperpyrexia, which reduce lot of preventable deaths. [e-ijd.org]

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