Journal
PAIN
Volume 153, Issue 10, Pages 2133-2139Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1016/j.pain.2012.07.012
Keywords
Neurotrophin; Pain; Sprouting; Sensory neuron; Cutaneous
Categories
Funding
- Medical Research Council of Great Britain
- Canadian Institutes of Health Research (CIHR)
- Ontario Research Fund - Research Excellence Program
- Krembil Foundation
- Canada Research Chair (tier 1) in Neuroplasticity and Pain and is an International Research Scholar for the Howard Hughes Medical institute
- MRC [G0901269] Funding Source: UKRI
- Medical Research Council [G0901269] Funding Source: researchfish
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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 naive 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. (C) 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
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