BDNF is essentially required for the early postnatal survival of nociceptors

abstract Article history:Received for publication 11 February 2009Revised 13 December 2009Accepted 5 January 2010Available online 11 January 2010Keywords:Neurotrophic factorNeurotrophinPeripheral nervous systemDorsal root gangliaSensory neuronSkin innervationNeuronal survivalBdnf knockout mice Neurotrophins promote the survival of specific types of neurons during development and ensure propermaintenance and function of mature responsive neurons. Significant effects of BDNF (Brain-DerivedNeurotrophic Factor) on pain physiology have been reported but the contribution of this neurotrophin to thedevelopment of nociceptors has not been investigated. We present evidence that BDNF is required for thesurvival of a significant fraction of peptidergic and non-peptidergic nociceptors in dorsal root ganglia (DRG)postnatally. Bdnf homozygous mutant mice lose approximately half of all nociceptive neurons during thefirst 2 weeks of life and adult heterozygotes exhibit hypoalgesia and a loss of 25% of all nociceptive neurons.Our in vitro analyses indicate that BDNF-dependent nociceptive neurons also respond to NGF and GDNF.Expression analyses at perinatal times indicate that BDNF is predominantly produced within sensory gangliaand is more abundant than skin-derived NGF or GDNF. Function-blocking studies with BDNF specificantibodies in vitro or cultures of BDNF-deficient sensory neurons suggest that BDNF acts in an autocrine/paracrine way to promote the early postnatal survival of nociceptors that are also responsive to NGF andGDNF. Altogether, the data demonstrate an essential requirement for BDNF in the early postnatal survival ofnociceptive neurons.© 2010 Elsevier Inc. All rights reserved.