title: A role for NT-3 in the hyperinnervation of neonatally wounded skin.
abstract: Neurotrophin-3 (NT-3) is a target-derived neurotrophic factor that regulates sensory neuronal survival and growth. Here we report that NT-3 plays a critical permissive role in cutaneous sensory nerve sprouting that contributes to pain and sensitivity following skin wounding in young animals. Sensory terminal sprouting in neonatally wounded dermis and epidermis is accompanied by increased NT-3 transcription, NT-3 protein levels, and NT-3 protein release 3-7 days post skin injury in newborn rats and mice. Functional blockade of NT-3 activity with specific antibodies greatly reduces sensory neurite outgrowth induced by wounded skin, but not by naïve skin, in dorsal root ganglion/skin co-cultures. The requirement for NT-3 for sensory terminal sprouting in vivo is confirmed by the absence of wound-induced hyperinnervation in heterozygous transgenic mice (NT-3(+/-)lacZ). We conclude that upregulation of NT-3 in neonatally wounded skin is a critical factor mediating the sensory nerve sprouting that underlies hypersensitivity and pain following skin injury.
authors.affiliation: Programme in Neurosciences & Mental Health, The Hospital for Sick Children, Toronto, ON, Canada Faculty of Dentistry, University of Toronto, Toronto, ON, Canada Department of Neuroscience, Physiology & Pharmacology, University College London, London, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Beggs
authors.forename: Debie
authors.initials: D
authors.lastname: Alvares
authors.forename: Andrew
authors.initials: A
authors.lastname: Moss
authors.forename: Gillian
authors.initials: G
authors.lastname: Currie
authors.forename: Jacqueta
authors.initials: J
authors.lastname: Middleton
authors.forename: Michael W
authors.initials: MW
authors.lastname: Salter
authors.forename: Maria
authors.initials: M
authors.lastname: Fitzgerald
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D051379:Mice; D008810:Mice, Inbred C57BL; D009416:Nerve Regeneration / Q000502:physiology*; D020933:Neurotrophin 3 / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000293:injuries / Q000294:innervation / Q000378:metabolism; D014950:Wounds, Penetrating / Q000378:metabolism*
chemical_list: D020933:Neurotrophin 3