NGF-dependent neurons and neurobiology of emotions and feelings: Lessons from congenital insensitivity to pain with anhidrosis

•Congenital insensitivity to pain with anhidrosis (CIPA) is a rare genetic disorder.•People with CIPA lack NGF-dependent neurons in otherwise intact systems.•They provide clues as to the functions of NGF-dependent neurons serve in humans.•NGF-dependent neurons play pivotal roles in interoception, homeostasis and stress response.•These neurons are also essential for neurobiology of our ‘emotions and feelings’. NGF is a well-studied neurotrophic factor, and TrkA is a receptor tyrosine kinase for NGF. The NGF–TrkA system supports the survival and maintenance of NGF-dependent neurons during development. Congenital insensitivity to pain with anhidrosis (CIPA) is an autosomal recessive genetic disorder due to loss-of-function mutations in the NTRK1 gene encoding TrkA. Individuals with CIPA lack NGF-dependent neurons, including NGF-dependent primary afferents and sympathetic postganglionic neurons, in otherwise intact systems. Thus, the pathophysiology of CIPA can provide intriguing findings to elucidate the unique functions that NGF-dependent neurons serve in humans, which might be difficult to evaluate in animal studies. Preceding studies have shown that the NGF-TrkA system plays critical roles in pain, itching and inflammation. This review focuses on the clinical and neurobiological aspects of CIPA and explains that NGF-dependent neurons in the peripheral nervous system play pivotal roles in interoception and homeostasis of our body, as well as in the stress response. Furthermore, these NGF-dependent neurons are likely requisite for neurobiological processes of ‘emotions and feelings’ in our species.