Studies on the interoception and autonomic neurons based on the molecular pathophysiology of congenital insensitivity to pain with anhidrosis

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Congenital insensitivity to pain with anhidrosis(CIPA) is a genetic disorder due to loss-of-function mutations in the NTRK1(TRKA) gene encoding TrkA, a receptor tyrosine kinase for NGF. Patients with CIPA lack NGF-dependent neurons, including polymodal receptors and sympathetic postganglionic neurons. Polymodal receptors play essential roles in interoception and report the physiological status of various tissues in the body to the brain. In response to interoception, the brain maintains homeostasis in the body via various neural mechanisms. Sympathetic neurons are indispensable for these mechanisms. Molecular pathophysiology of CIPA indicates that NGF-dependent neurons are essential for the establishment of neural networks for interoception and homeostasis, playing crucial roles in the brain-body interactions.