Paroxysmal intense pain (Paroxysmal extreme pain disorder) - Gen SCN9A.

Paroxysmal intense pain is a disorder characterized by skin redness, heat, and episodes of intense pain in various parts of the body. In affected individuals, episodes of pain usually last from seconds to minutes, but in some cases can last for hours. These episodes can begin in childhood. In general, at the beginning of life, pain is concentrated at the bottom of the body, particularly around the rectum, and generally is caused by a bowel movement. Some children may have constipation, which is believed to be due to fear of provoking an attack of pain. In young children, episodes of pain may also be accompanied by convulsions, slow heart rate or apnea.

As the age of these individuals progresses, pain attacks begin to affect the head and face, especially the eyes and jaw. Triggers these attacks of pain include changes in temperature (like a cold wind), emotional distress, spicy foods food and cold drinks consumption. This disease is considered a form of peripheral neuropathy, affecting the peripheral nervous system, connecting the brain and spinal cord to the muscles and the cells that detect sensation like touch, smell , and pain.

This process is due to mutations in the SCN9A gene, located on the long arm of chromosome 2 (2q24). This gene encodes the alpha subunit of a sodium channel Nav1.7 called. Sodium channels transport sodium ions into cells and play a key role in the ability of a cell to generate and transmit electrical signals. These channels are in nerve cells called nociceptors that transmit pain signals to the spinal cord and brain. The nociceptors are part of the peripheral nervous system, connecting the brain and spinal cord cells that detect sensation like touch, smell , and pain. Nociceptors are mainly involved in the transmission of pain signals. Nociceptors centers, known as the cell bodies are found in the dorsal root ganglion. Axons transmit information back to the dorsal root ganglion, which is then sent to the brain. Nav1.7 sodium channels are also found in olfactory sensory neurons.

They have identified approximately 10 mutations in the SCN9A gene, giving rise to intense breakthrough pain. These mutations change the amino acid alpha subunit of the sodium channel Nav1.7. As a result, the sodium channel is not completely closed when idle, allowing sodium ions to flow abnormally in nociceptors. This increase in sodium ions improves the transmission of pain signals, leading to attacks of pain exhibited by people with paroxysmal pain intenso.Se know why these attacks cause pain other features of the disease such as seizures and changes in breathing.

This disease is inherited in an autosomal dominant, which means that a copy of the altered gene in each cell is sufficient for alteration is expressed. In most cases, an affected person has a parent with the disease.

Tests in IVAMI: in IVAMI perform detection of mutations associated with severe paroxysmal pain, by complete PCR amplification of the exons of the SCN9A gene, and subsequent sequencing.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).