Nerve Growth Factor and the Physiology of Pain: Lessons from Congenital Insensitivity to Pain with Anhidrosis

Autor: Indo, Yasuhiro
Jazyk: angličtina
Rok vydání: 2012
Předmět:
Zdroj: Clinical Genetics. 82(4):341-350
ISSN: 0009-9163
Popis: Congenital insensitivity to pain with anhidrosis (CIPA) is an autosomal recessivegenetic 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 thesurvival and maintenance of NGF-dependent neurons, including primary afferentneurons with thin fibers and sympathetic postganglionic neurons, during development.NGF is also considered to be an inflammatory mediator associated with pain, itch andinflammation 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 inNGF-TrkA signal transduction lead to the failure of survival of various NGF-dependentneurons. As a result, patients with CIPA lack NGF-dependent neurons. Recent studieshave revealed that mutations in the NGFB gene-encoding NGF protein also causecongenital insensitivity to pain.Using the pathophysiology of CIPA as a foundation, this review investigates the waysin which NGF-dependent neurons contribute to interoception, homeostasis andemotional responses and, together with the brain, immune and endocrine systems, playcrucial roles in pain, itch and inflammation.The NGF-TrkA system is essential for the establishment of neural networks forinteroception, homeostasis and emotional responses. These networks mediate reciprocalcommunication between the brain and the body in humans.
Databáze: OpenAIRE
Externí odkaz: