Primary Afferent-Derived BDNF Contributes Minimally to the Processing of Pain and Itch

eNeuro. 2018 Dec 26;5(6):ENEURO.0402-18.2018. doi: 10.1523/ENEURO.0402-18.2018. eCollection 2018 Nov-Dec.


BDNF is a critical contributor to neuronal growth, development, learning, and memory. Although extensively studied in the brain, BDNF is also expressed by primary afferent sensory neurons in the peripheral nervous system. Unfortunately, anatomical and functional studies of primary afferent-derived BDNF have been limited by the availability of appropriate molecular tools. Here, we used targeted, inducible molecular approaches to characterize the expression pattern of primary afferent BDNF and the extent to which it contributes to a variety of pain and itch behaviors. Using a BDNF-LacZ reporter mouse, we found that BDNF is expressed primarily by myelinated primary afferents and has limited overlap with the major peptidergic and non-peptidergic subclasses of nociceptors and pruritoceptors. We also observed extensive neuronal, but not glial, expression in the spinal cord dorsal horn. In addition, because BDNF null mice are not viable and even Cre-mediated deletion of BDNF from sensory neurons could have developmental consequences, here we deleted BDNF selectively from sensory neurons, in the adult, using an advillin-Cre-ER line crossed to floxed BDNF mice. We found that BDNF deletion in the adult altered few itch or acute and chronic pain behaviors, beyond sexually dimorphic phenotypes in the tail immersion, histamine, and formalin tests. Based on the anatomical distribution of sensory neuron-derived BDNF and its limited contribution to pain and itch processing, we suggest that future studies of primary afferent-derived BDNF should examine behaviors evoked by activation of myelinated primary afferents.

Keywords: BDNF; dorsal root ganglia; itch; neuropathic pain; spinal cord; transgenic knock-out.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Afferent Pathways / metabolism*
  • Animals
  • Antineoplastic Agents, Phytogenic / toxicity
  • Brain-Derived Neurotrophic Factor / genetics
  • Brain-Derived Neurotrophic Factor / metabolism*
  • Calcitonin Gene-Related Peptide / metabolism
  • Calcium-Binding Proteins / metabolism
  • Disease Models, Animal
  • Freund's Adjuvant / toxicity
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology*
  • Genotype
  • Histamine / toxicity
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microfilament Proteins / metabolism
  • Nerve Fibers, Myelinated / metabolism*
  • Nerve Tissue Proteins / metabolism
  • Neurons / drug effects
  • Neurons / metabolism
  • Paclitaxel / toxicity
  • Pain / chemically induced
  • Pain / metabolism*
  • Pain Measurement
  • Pruritus / chemically induced
  • Pruritus / metabolism*


  • Aif1 protein, mouse
  • Antineoplastic Agents, Phytogenic
  • Brain-Derived Neurotrophic Factor
  • Calcium-Binding Proteins
  • Microfilament Proteins
  • Nerve Tissue Proteins
  • Histamine
  • Freund's Adjuvant
  • Calcitonin Gene-Related Peptide
  • Paclitaxel