Nerve growth factor, interoception, and sympathetic neuron: lesson from congenital insensitivity to pain with anhidrosis

Auton Neurosci. 2009 May 11;147(1-2):3-8. doi: 10.1016/j.autneu.2009.01.008. Epub 2009 Feb 8.

Abstract

Nerve growth factor (NGF) is a well-known neurotrophic factor essential for the survival and maintenance of sensory and sympathetic neurons. Congenital insensitivity to pain with anhidrosis (CIPA) is a genetic disorder due to loss-of-function mutations in the NTRK1 (also known as TRKA) gene encoding TrkA, a receptor tyrosine kinase for NGF. Patients with CIPA provide us a rare opportunity to explore the developmental and physiological function of the NGF-dependent neurons in behavior, cognitive, and mental activities that are not available in animal studies. Here, I discuss the significance of findings that patients with CIPA lack NGF-dependent neurons, including interoceptive polymodal receptors, sympathetic postganglionic neurons, and probably several types of neurons in the brain. They also exhibit characteristic emotional behavior or problems. Together, the NGF-TrkA system is essential for the establishment of a neural network for interoception and homeostasis that may underlie 'gut feelings'. Thus, NGF-dependent neurons play a crucial role in emotional experiences and decision-making processes. Prospective studies focused on these neurons might provide further insights into the neural basis of human emotion and feeling.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Affect / physiology
  • Animals
  • Autonomic Nervous System Diseases / genetics
  • Autonomic Nervous System Diseases / metabolism
  • Autonomic Nervous System Diseases / physiopathology*
  • Emotions / physiology
  • Hereditary Sensory and Autonomic Neuropathies / genetics
  • Hereditary Sensory and Autonomic Neuropathies / metabolism
  • Hereditary Sensory and Autonomic Neuropathies / physiopathology*
  • Humans
  • Mood Disorders / genetics
  • Mood Disorders / metabolism
  • Mood Disorders / physiopathology*
  • Mutation / genetics
  • Nerve Growth Factor / metabolism*
  • Nociceptors / metabolism
  • Receptor, trkA / genetics
  • Visceral Afferents / metabolism
  • Visceral Afferents / physiopathology*

Substances

  • Nerve Growth Factor
  • Receptor, trkA