The author reports no conflict of interest.
Nerve growth factor and the physiology of pain: lessons from congenital insensitivity to pain with anhidrosis
Version of Record online: 13 AUG 2012
© 2012 John Wiley & Sons A/S
Volume 82, Issue 4, pages 341–350, October 2012
How to Cite
Nerve growth factor and the physiology of pain: lessons from congenital insensitivity to pain with anhidrosis..
- Issue online: 11 SEP 2012
- Version of Record online: 13 AUG 2012
- Manuscript Revised: 23 JUL 2012
- Manuscript Accepted: 23 JUL 2012
- Manuscript Received: 30 MAY 2012
- Japan Society for the Promotion of Science (JSPS) (KAKENHI)
- Ministry of Health, Labour and Welfare: Health and Labour Science Research Grants (Research on Intractable Diseases)
- NGF-dependent primary afferent neurons;
- NTRK1 gene;
- polymodal receptors;
- receptor tyrosine kinase for NGF;
- sympathetic neurons;
- TrkA receptor
Congenital insensitivity to pain with anhidrosis (CIPA) is an autosomal recessive genetic disorder characterized by insensitivity to pain, anhidrosis (the inability to sweat) and mental retardation. Nerve growth factor (NGF) is a well-known neurotrophic factor essential for the survival and maintenance of NGF-dependent neurons, including primary afferent neurons with thin fibers and sympathetic postganglionic neurons, during development. NGF is also considered to be an inflammatory mediator associated with pain, itch and inflammation in adults. CIPA results from loss-of-function mutations in the NTRK1 gene-encoding TrkA (tropomyosin-related kinase A), a receptor tyrosine kinase for NGF. Defects in NGF-TrkA signal transduction lead to the failure of survival of various NGF-dependent neurons. As a result, patients with CIPA lack NGF-dependent neurons. Recent studies have revealed that mutations in the NGFB gene-encoding NGF protein also cause congenital insensitivity to pain. Using the pathophysiology of CIPA as a foundation, this review investigates the ways in which NGF-dependent neurons contribute to interoception, homeostasis and emotional responses and, together with the brain, immune and endocrine systems, play crucial roles in pain, itch and inflammation. The NGF-TrkA system is essential for the establishment of neural networks for interoception, homeostasis and emotional responses. These networks mediate reciprocal communication between the brain and the body in humans.