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Congenital insensitivity to pain with anhidrosis (CIPA) is an autosomal recessive genetic disorder caused by loss\u2010of\u2010function mutations in<jats:italic>NTRK1<\/jats:italic>, the gene encoding a receptor tyrosine kinase for NGF, TrkA. Mutations in<jats:italic>NTRK1<\/jats:italic>cause the selective loss of NGF\u2010dependent neurons in otherwise intact systems. NGF\u2010dependent primary afferents are thinly myelinated A\u03b4 or unmyelinated C\u2010fibers that are dependent on the NGF\u2013TrkA system during development. In CIPA, the lack of pain and the presence of anhidrosis (inability to sweat) are due to the absence of both NGF\u2010dependent primary afferents and sympathetic postganglionic neurons, respectively. These peripheral neurons form an interface between the nervous system and the \u2018body\u2010proper\u2019 and play essential roles in the interoception and sympathetic regulation of various tissues or organs. Patients with CIPA also show mental retardation and characteristic behaviors and are probably neuron\u2010deficient within the brain. However, the functions of NGF\u2010dependent neurons in the brain are controversial, both in animal and in human studies. This review focuses on various brain regions that express TrkA<jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content>, based on data from the<jats:italic>Allen Human Brain Atlas<\/jats:italic>, and discusses putative neuronal networks related to these brain regions in humans. A better understanding the distribution of NGF\u2010dependent neurons in the brain will provide a framework for further studies to investigate pain, interoception and emotional responses. Furthermore, strategies targeting the molecular mechanisms through which the NGF\u2013TrkA system functions may provide hope for the development of novel analgesics.<\/jats:p>","DOI":"10.1111\/ejn.12448","type":"journal-article","created":{"date-parts":[[2014,2,4]],"date-time":"2014-02-04T15:25:29Z","timestamp":1391527529000},"page":"375-391","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Neurobiology of pain, interoception and emotional response: lessons from nerve growth factor\u2010dependent neurons"],"prefix":"10.1111","volume":"39","author":[{"given":"Yasuhiro","family":"Indo","sequence":"first","affiliation":[{"name":"Department of Pediatrics Kumamoto University Hospital Honjo 1\u20101\u20101, Chuou\u2010ku Kumamoto 860\u20108556 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,2,4]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"crossref","DOI":"10.1093\/oso\/9780198505013.001.0001","volume-title":"The Amygdala: A Functional Analysis","author":"Aggleton J.P.","year":"2000"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2005-3032"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.09.028"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.20095"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/123.3.601"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.1997.6443"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.npp.1301294"},{"key":"e_1_2_9_9_1","unstructured":"Bowden D.M.(2002)NeuroNames. 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