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.

journal_name

Pain

journal_title

Pain

authors

Beggs S,Alvares D,Moss A,Currie G,Middleton J,Salter MW,Fitzgerald M

doi

10.1016/j.pain.2012.07.012

subject

Has Abstract

pub_date

2012-10-01 00:00:00

pages

2133-2139

issue

10

eissn

0304-3959

issn

1872-6623

pii

00006396-201210000-00022

journal_volume

153

pub_type

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