1. Introduction

This video clip is a segment from Anderson Cooper 360 on CNN about Congenital insensitivity to pain with anhidrosis (CIPA), also referred to as hereditary sensory and autonomic neuropathy type 4 (HSAN-IV). It is considered the most severe out of all HSAN types. CIPA is a rare hereditary neurological disorder where the patient is unable to feel pain, temperature and unable to sweat (anhidrosis). In the video clip, it discusses the experience of a four year old child, Roberto, diagnosed with this disorder. From the moment of birth, Roberto was unable to feel pain. He was unable to comprehend the self-inflicted injuries done to his body. As a toddler he teethed on his fingers, tongue and lips; shedding blood and unaware of the damage done. The inability to feel pain is a danger to the patient itself as pain acts as a warning sign to stop the body from causing further damage.

CIPA was chosen as our topic of research because it is a rare disorder. Since a majority of rare disorders are not well known and have limited information, we thought it was an intriguing topic to research. Furthermore, by choosing this topic we thought it will also raise awareness of this disorder. In society, the concept of pain has been regarded as something people thought was better without; the idea of having a pain-free life may seemed ideal, but for those with CIPA it is vital for their survival. We thought it was appropriate to enlighten others of the importance of pain, as it is the body’s natural defense mechanism to prevent further damage to the body.

2. Neuroscientific Context

2.1 Background

Congenital insensitivity to pain (CIPA), also called hereditary sensory and autonomic neuropathy (HSAN), is a rare neurological disorder of the nervous system with no cure. It is an autosomal recessive disorder - a genetic mutation in an autosome (a non-sex chromosome) that only occurs when either both parents are affected or are carriers of the recessive genes which are then passed on homozygously to the child (Kaneshiro, 2012). It is commonly accompanied by hyperactivity and anhidrosis. CIPA results in the patient’s inability to sense extreme coldness, heat, or pain and even nerve related sensations such as hunger and the need to urinate (Nagasako et al., 2003). The lack of pain patients experience often leads to self-mutilation, bone fractures and eye
Figure 1. The 5 types of HSAN
Figure 1. The 5 types of HSAN

related problems (infection due to excessive rubbing/scratching) . CIPA is often seen as a condition exhibited in children as the life expectancy of patients with CIPA is very low. Most infants don’t pass 3 years and those that do, commonly do not make it past 25 years. The reason for death is due to the wear and tear done to their bodies as well as hyperthermia (Mardy et al., 2001).

There are five types of HSAN, all of which typically feature reduction in function of peripheral sensory nerves. Type 1 (HSAN-I) is the most common type, characterized by a loss of sensation in lower extremities, sweating abnormalities, ulcerations and bone deterioration (Auer-Grumbach, 2008). Type 2 (HSAN-II) ulcerations of fingers and feet, affected pain sensation, reflexes reduced, neuropathic joint degeneration and loss of myelinated fibres. Type 3 (HSAN-III) features include, hypotonia, hypothermia, poor coordination and temperature regulation with indifference to pain. Type 4 (HSAN-IV) commonly characterized by congenital insensitivity to pain with anhidrosis with reduced or absent small unmyelinated nerve fibres. Type 5 (HSAN-V) consists of congenital insensitivity to pain with partial anhidrosis (Axelrod et al., 2007).

2.2 Physiological Mechanisms

The perception of pain is usually evoked at pressures and temperatures extreme enough to cause potential tissue damage and also by toxic molecules and inflammatory mediators. These high threshold stimuli are detected by specialised peripheral sensory neurons known as nociceptors which are abundant in the Peripheral Pain Pathway. When extremes in temperature and pressure are detected by the nociceptors, the stimuli is transduced into electrical signals which are then fired through axons as action potentials to the Central Pain Pathway (Dubin & Patapoutian, 2010).

Figure 2. The neuronal pathways involved
Figure 2. The neuronal pathways involved

There are two major central pathways for pain and temperature sensation: the spinothalamic tract, which is the major ascending pathway, and the trigerminal pain and temperature system, which carries the sensory information from the face to the brain. In the spinothalamic tract, the signals that are sent through the central axons travel to the spinal cord via the dorsal roots. Upon reaching the dorsal horn, axons in Lissauer's tract ascend and descend for one or two spinal segments before penetrating the grey matter and branching off to neurons in divisions of the spinal grey matter. The axons then ascend in the anterolateral quadrant of the spinal cord to the brainstem and thalamus where the information is sent to the primary somatosensory cortex. The primary somatosensory cortex receives this somatosensory input from the thalamus and encodes information related to the discriminative aspects of pain (DaSilva et al., 2002). When pain is discriminated, the hypothalamus can relay a response through the descending pathway (Purves et al., 2001). For example, if acute pain is detected on your finger, the signals of this stimulus will be sent to the motor cortex to facilitate muscle contractions to remove your finger from the object causing this pain.

Figure 3. Dermatome of the Trigerminal Nerves

The trigerminal pain and temperature system facilitates such a response in a similar fashion through the trigerminal nerves. However, instead of traveling through the spinal cord, noxious stimuli detected is carried to the thalamus by the ophthalmic nerve (V1), maxillary nerve (V2) or the ​mandibular nerve (V3) depending on the location on the face.

However, people with CIPA do not detect pain with the Peripheral Nervous System due to mutations in the tyrosine kinase receptor gene (TRKA), a gene that codes for receptor tyrosine kinase (RTK). These receptors facilitate the production of Nerve Growth Factors (NGF) which are proteins vital in the formation and maturation of peripheral sympathetic and sensory neurons, such as nociceptive nerve cells (Mardy et al., 2001). The NGF has a high affinity for RTK; its binding to RTK promotes the survival and maintenance of sensory and sympathetic neurons during embryogenesis (the formation and development of an embryo). Due to the mutation in TRKA, RTK is no longer encoded and subsequently, the NGF proteins cannot bind to the pain receptors to keep them functioning. The nociceptors become defective so painful stimuli cannot be detected and signaled to the spinothalamic tract or the trigerminal pain and temperature system. A study conducted on mice showed that those lacking the gene responsible for NGF receptor, RTK, exhibited a phenotype similar to that of a patient with CIPA. Recent research has also found new NGF-responsive cells, including lymphocytes and cellular elements of the endocrine system (Parvari et al., 2003; Sztriha et al., 2001).

2.3 Causes

Causes of Congenital insensitivity to pain and anhidrosis (CIPA) can vary from case to case, however the cause can commonly be attributed to neuropathy (defective nociception) and genetic mutations of vital receptors. The human TRKA gene, located on chromosome 1q21–q22, can cause CIPA because of the frameshift, splice-site or nonsense mutations in the NRTK1 gene. As mentioned above, this mutation prevents the normal encoding of RTK receptors responsible for producing proteins that nociceptors are dependent upon. This lack of functionality creates the absence of pain and temperature detection.

Patients who suffer from CIPA have shown a lack of primary sensory neurons in Lissauer’s tract the ganglia and the dorsal roots. Patients also lack cells such as small ganglion in the dorsal ganglia. In addition to lacking these structures, small myelinated fibers and nonmyelinated fibres of the dorsal ganglia are absent. The dorsal ganglia and root are important in the relaying of sensory afferent nerves. The absence of these structures form the basis of the insensitivity to pain and anhidrosis is caused by a similar lack of innervation, though of eccrine sweat glands by the sympathetic nerves (Parvari et al., 2003). Although individuals with CIPA appear to have normal sweat glands, they have an inability to produce sweat. The lack of sweating associated with anhidrosis is due to the inability of the skin to sense temperature changes in the internal and external environment.

2.4 Treatment

Unfortunately there is no cure to CIPA or HSAN. However, treatment is most commonly in the form of early education of relatives and the patient in later years. Since children with CIPA or HSAN are prone to painless injuries, extreme care and medical supervision is required from a very young age. 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. A common habit of babies with HSAN
Figure 4. A common habit of babies with HSAN

Maintaining a regular eating schedule is also sometimes challenging, for those that suffer from CIPA do not feel hunger pains and children must often be forced to eat meals at regular intervals and IV may be needed in severe cases. Protective eye wear is also commonly worn to prevent infection or inflammation due to excessive rubbing and scratching of the cornea. The biggest threat to those that suffer from CIPA is the anhidrosis that is associated with the disorder. Since the patients are not able to regulate their body temperature normally through sweating, hyperthermia can ensue and lead to febrile seizures and, in extreme cases, death. Keeping the body temperature within safe margins is vital and must be carefully monitored.

Pharmaceutically, naloxone is used to prevent inactivation of neurons that receive noxious signals, but this does not work for all cases. Recently, prenatal diagnosis has become available as an option for those families affected. Since cases of CIPA and HSAN can vary in symptoms, there is no universal treatment.

3. Analysis

3.1 Target Audience

The media item aired in 2006 on Cable News Network (CNN), a United States channel that provides twenty four hour television news coverage (Yu Sha 2005.), and is broadcasted internationally. CNN appeals to the general public, and age demographic of 25 to 65+(

This particular segment is targeted to stimulate the population’s interests, and inform the public about the current issues of congenital insensitivity to pain (CIPA) with anhidrosis, specifically to 4-year-old Roberto Salazar, and his mother.

This media item is also featured on youtube, uploaded by the user HelpRoberto ( Through this, it appeals to, and becomes available for international and global audiences.

3.2 Purpose and Bias

The segment from ‘Anderson Cooper 360’ was broadcasted to apprise the general public about CIPA with anhidrosis, but characteristically targets mothers, as Roberto Salazar’s mother is featured responding emotionally to her son’s condition. The segment was created to promote the understanding of this condition as well as the influence and hardships it has on the victim’s parents. It focuses on the life of Roberto Salazar, from birth till present, and only compares his condition to others statistically, rather than another in-depth feature.
The user HelpRoberto, uploaded the video onto youtube for an additional campaign to the awareness of the disorder, as well as a plea for anyone who wishes to support Roberto. The user, HelpRoberto, also features other segments on shows such as ‘Strictly Dr. Drew’ on Discovery health, and a Hispanic television show ‘al Rojo Vivo con Maria Celeste’. This establishes the intention of the video on youtube to gain interest and awareness of Roberto's condition.

3.3 Quality of Information and Current Understanding

Felicia Axelrod, M.D., who is featured in the media item, explains hereditary sensory and autonomic neuropathy (HSAN) briefly and the need for the perception and awareness of pain stimuli. She is a Professor of Dysautonomia Treatment and Research as well as Director of Dysautonomia Program, and specialised in the areas of Pediatrics and Neurology ( She adheres to the misconception of the idyllic beliefs of a pain-free world, and explains the necessity for pain recognition to procest ourselves from harm. With her qualifications, and her communications between her patient, Roberto, the audience are endorsed to trust her findings and verdicts of the disorder.

The commentator and journalist, Anderson Cooper, elucidates the HSAN disorder to be a group of 7 rare disorders, and affects the autonomic nervous system that regulates blood pressure and heart rate, explaining that children with these diseases have little to no pain. 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. He indicates that Roberto’s condition is the most severe and is coupled with hyperactivity, where more than half the victims die by the age of 3. And as an experienced journalist, the responders can trust the information they are provided with.

The current scientific understanding today, establishes that there are five types of HSAN, and that the disorder is genetic, but is also autosomal recessive (Mardy S., et al. 2001.). Scientists have also inferred the location to be in the gene encoding the neurotrophic tyrosine kinase receptor (NTRK1 gene) (Shatzky, S.,. et al. 2000.),( Treatment is also rare, and only management and surveillance is recommended.(Axelrod F.B. et al. 2008.)

3.4 Overall Analysis

The information provided by the media item is not detailed with the disease characteristics, but gives a brief overall summary to appeal to the general population, and attracts the attention and sympathy of viewers to the condition of Roberto Salazar, as well as his mother on a personal level.

4. Appendix

The selection of this topic was after searching through many other topics including prosopagnosia and ataxia to name a few. It was difficult to decide on a particular topic as all interested us and we didn’t particular had an area we were extremely passionate in. After searching through media items we stumbled upon video clips on CIPA, which perked all of our interest. All of us had vaguely heard of such a disorder, but we never thought it was such a rare and horrifying condition. It was quite disconcerting witnessing toddlers with CIPA slamming into the corners of tables and picking themselves up with a smile on their face. Despite it being horrifying, we thought it would be intriguing to uncover the causes of such a disorder.

The media item came from a U.S. news channel called Cable News Network (CNN) which is considered a reliable source as it is aired globally. Although the video is a few years old, it provided a brief overview of CIPA as well as a basic biological explanation of it. The other videos had less scientific information compared to our chosen clip.

The selection of resources for this reported was chosen for its relevance and its reliable origin. We first used Google to search for sites such as Wikipedia and to gather and build a general understanding of HSAN. This preliminary research gave us a foundation to work with and helped to identify the key issues we needed to look for in research articles. Our methods of research became progressively more specific and we moved onto Google Scholar to find recent papers on the topic. This was achieved by making sure that our search results had a time frame (2000 - 2012) criteria. Google Scholar then lead us to many primary and secondary research articles.

The general feedback from the review comments that we gathered indicated we needed to mostly focus on the neuroscientific content section. In particular, the sentence structure, grammar and clarity of the neuroscientific content section. The group members responsible for this edited the parts accordingly by correcting grammatical errors and rewording sentences and their structures to improve clarity - specifically, the last paragraph in the physiology section. Some comments also mentioned the pictures used were too small so we readjusted the position and size of the images for easier viewing. Our referencing was also a concern, so we made sure to include all references this time around as the draft wiki had been submitted with missing references.

5. References

Auer-Grumbach M (2008). Hereditary sensory neuropathy type I. Orphanet Journal of Rare Diseases 3(1): 7.

Axelrod F, Gold-von Simson G (2007). Hereditary sensory and autonomic neuropathies: types II, III, and IV. Orphanet Journal of Rare Diseases 2(1): 39.

Axelrod FB, Simson GG, Oddoux C (2008). Hereditary Sensory and Autonomic Neuropathy IV. GeneReviews (online). ( [Accessed: 08/08/2012]

DaSilva AFM, Becerra L, Makris N, Strassman A, Gonzalez RG, Geatrakis N and Borsook D (2002). Somatotopic Activation in the Human Trigeminal Pain Pathway, The Journal of Neuroscience. 22(18): 8183-8192

Dubin AE and Patapoutian A (2010). Nociceptors: the sensors of the pain pathway. Journal of Clinical Investigation. 120(11):3760

Kaneshiro NK (2012). Autosomal Recessive. [ONLINE] Available at: [Accessed 20 September 12].

Mardy S, Miura Y, Endo F, Matsuda I, Indo Y (2001). Congenital insensitivity to pain with anhidrosis (CIPA): effect of TRKA (NTRK1) missense mutations on autophosphorylation of the receptor tyrosine kinase for nerve growth factor. Human Molecular Genetics. 10(3) 179-188.

Nagasako EM, Oaklander AL, Dworkin RH (2003). Congenital insensitivity to pain: an update. Pain 101(3): 213-219.

Parvari R, Moses S (2003). Congenital Insensitivity to Pain with Anhidrosis (CIPA). In: Editors-in-Chief: Michael JA, Robert BD. Encyclopedia of the Neurological Sciences, edn. New York: Academic Press. pp 764-765.

Purves D, Augustine GJ, Fitzpatrick D, et al. (2001). Central Pain Pathways: The Spinothalamic Tract. Neuroscience. 2nd edition. Sunderland (MA): Sinauer Associates. Available from:

Shatzky S, Moses S, Levy J, Pinsk V, Hershkovitz E, Herzog L, Shorer Z, Luder A and Parvari R (2000). Congenital insensitivity to pain with anhidrosis (CIPA) in Israeli-Bedouins: Genetic heterogeneity, novel mutations in the TRKA/NGF receptor gene, clinical findings, and results of nerve conduction studies. Am. J. Med. Genet. Vol 92(5) Pp. 325-360.

Sztriha L, Lestringant GG, Hertecant J, Frossard PM, Masouyé I (2001). Congenital insensitivity to pain with anhidrosis. Pediatric Neurology 25(1): 63-66.

Yu Sha (2005). CNN changed news - for better and worse. Taipei Times. ( [Accessed:08/08/2012] [Accessed: 07/08/2012] [Accessed: 07/08/2012]