title: [Nerve growth factor and the physiology of pain: the relationships among interoception, sympathetic neurons and the emotional response indicated by the molecular pathophysiology of congenital insensitivity to pain with anhidrosis].
abstract: Nerve growth factor (NGF) is a neurotrophic factor essential for the survival and maintenance of neurons. Congenital insensitivity to pain with anhidrosis (CIPA) is caused by loss-of-function mutations in NTRK1, which encodes a receptor tyrosine kinase, TrkA, for NGF. Mutations in NTRK1 cause the selective loss of NGF-dependent neurons, including both NGF-dependent primary afferents and sympathetic postganglionic neurons, in otherwise intact systems. The NGF-dependent primary afferents are thinly myelinated AΔ or unmyelinated C-fibers that are dependent on the NGF-TrkA system during development. NGF-dependent primary afferents are not only nociceptive neurons that transmit pain and temperature sensation, but also are polymodal receptors that play essential roles for interoception by monitoring various changes in the physiological status of all tissues in the body. In addition, they contribute to various inflammatory processes in acute, chronic and allergic inflammation. Together with sympathetic postganglionic neurons, they maintain the homeostasis of the body and emotional responses via interactions with the brain, immune and endocrine systems. Pain is closely related to emotions that accompany physical responses induced by systemic activation of the sympathetic nervous system. In contrast to a negative image of emotions in daily life, Antonio Damasio proposed the 'Somatic Marker Hypothesis', wherein emotions play critical roles in the decision-making and reasoning processes. According to this hypothesis, reciprocal communication between the brain and the body-proper are essential for emotional responses. Using the pathophysiology of CIPA as a foundation, this article suggests that NGF-dependent neurons constitute a part of the neuronal network required for homeostasis and emotional responses, and indicates that this network plays important roles in mediating the reciprocal communication between the brain and the body-proper.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Indo
mesh_terms: D004644:Emotions; D006801:Humans; D007007:Hypohidrosis / Q000209:etiology*; D065812:Interoception; D020932:Nerve Growth Factor / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D010146:Pain / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology*
chemical_list: D020932:Nerve Growth Factor