The Contribution of Schwann cell TRPA1 to familial episodic pain syndrome

Familial episodic pain syndrome (FEPS) is a rare genetic disorder that affects the peripheral nervous system, i.e. the nerves, characterized by intense, diffuse, and episodic pain, which occurs mainly in the upper body and limbs. It can affect several members of the same family and is triggered by numerous events, such as fatigue, cold, fasting, weather changes, and physical stress. The TRPA1 protein found in the membrane of the sensory neurons controls the transmission of painful sensations. It allows to perceive the spicy sensation, sometimes painful, of wasabi, which has recently been the subject of news worldwide because it belongs to the family of proteins that led David Julius to win the 2021 Nobel Prize for Medicine. In 2010, studying a Colombian family with FEPS, it was shown that a gene mutation of TRPA1 was the cause of the syndrome. In the last 5 years, we have studied the role of TRPA1 in pain in a particular cell, which surrounds the nerves, the Schwann cell. Studies have shown that TRPA1 expressed in Schwann cells activates nerve inflammation in various animal pain models, such as cancer, alcoholism, and trauma. In this project, we propose to study Schwann cells and develop transgenic mice that express the TRPA1 protein with the mutation responsible for FEPS, to study the cellular and molecular mechanisms that produce pain attacks. Our proposal is to identify the targets for drugs that, by blocking the activity of TRPA1 in Schwann cells, can treat the pain exacerbation affecting FEPS patients.