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Nerve growth factor (<jats:styled-content style=\"fixed-case\">NGF<\/jats:styled-content>) is a well\u2010known neurotrophic factor essential for the survival and maintenance of <jats:styled-content style=\"fixed-case\">NGF<\/jats:styled-content>\u2010dependent neurons, including primary afferent neurons with thin fibers and sympathetic postganglionic neurons, during development. <jats:styled-content style=\"fixed-case\">NGF<\/jats:styled-content> is also considered to be an inflammatory mediator associated with pain, itch and inflammation in adults. <jats:styled-content style=\"fixed-case\">CIPA<\/jats:styled-content> results from loss\u2010of\u2010function mutations in the <jats:italic><jats:styled-content style=\"fixed-case\">NTRK1<\/jats:styled-content><\/jats:italic> gene\u2010encoding <jats:styled-content style=\"fixed-case\">TrkA<\/jats:styled-content> (tropomyosin\u2010related kinase A), a receptor tyrosine kinase for <jats:styled-content style=\"fixed-case\">NGF<\/jats:styled-content>. Defects in <jats:styled-content style=\"fixed-case\">NGF\u2010TrkA<\/jats:styled-content> signal transduction lead to the failure of survival of various <jats:styled-content style=\"fixed-case\">NGF<\/jats:styled-content>\u2010dependent neurons. As a result, patients with <jats:styled-content style=\"fixed-case\">CIPA<\/jats:styled-content> lack <jats:styled-content style=\"fixed-case\">NGF<\/jats:styled-content>\u2010dependent neurons. Recent studies have revealed that mutations in the <jats:italic>NGFB<\/jats:italic> gene\u2010encoding NGF protein also cause congenital insensitivity to pain. Using the pathophysiology of CIPA as a foundation, this review investigates the ways in which NGF\u2010dependent 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\u2010TrkA 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.<\/jats:p>","DOI":"10.1111\/j.1399-0004.2012.01943.x","type":"journal-article","created":{"date-parts":[[2012,8,13]],"date-time":"2012-08-13T08:40:46Z","timestamp":1344847246000},"page":"341-350","source":"Crossref","is-referenced-by-count":73,"title":["Nerve growth factor and the physiology of\u00a0pain: lessons from congenital insensitivity to pain with anhidrosis"],"prefix":"10.1111","volume":"82","author":[{"given":"Y","family":"Indo","sequence":"first","affiliation":[{"name":"Department of Pediatrics Kumamoto University Hospital  Kumamoto 860\u20108556 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