# Peripheral BDNF drives primary afferent hyperexcitability and pain hypersensitivity

> **NIH NIH R21** · EMORY UNIVERSITY · 2020 · $425,189

## Abstract

Project Summary/Abstract
Brain-derived neurotrophic factor (BDNF) is implicated in numerous cellular actions that are both
adaptive and maladaptive in nature. For nearly two decades, it has been proposed that BDNF
signaling through its high affinity receptor TrkB, plays a role in inflammatory and nerve injury-
induced neuropathic pain. However, whether BDNF-TrkB signaling is also critically involved in the
development or maintenance of chronic neuropathic pain after spinal cord injury (SCI) remains
unsolved. We hypothesize that cutaneous BDNF promotes primary afferent hyperexcitability and
thus pain after SCI, thereby arguing that peripheral, but not central, BDNF signaling is more critical
to the expression of SCI-induced pain.
In SA1, behavioral studies will compare the effect of peripheral BDNF signaling on formalin-
induced inflammatory pain, and neuropathic pain after peripheral nerve and spinal cord injury.
Experiments will be undertaken in mice with a mutated TrkB receptor (TrkBF616A mice) that allows
selective and reversible blockade of BDNF signaling, and mice in which BDNF is selectively
knocked out in primary afferents (BDNF-cKO mice) - derived from crossing BDNFFl/Fl mice with
Advillin-Cre mice. In SA2, an ex-vivo skin-nerve electrophysiology preparation will be used to
examine the effect of increased BDNF in the skin on neural activity evoked by stimulation of
primary afferents innervating the trunk skin, in these transgenic strains. We will also undertake
cellular assessment to examine changes in the expression of BDNF, TrkB and several key
downstream signaling proteins in the skin after inflammatory and neuropathic pain.
This novel exploratory study will be the first to identify the important and specific role peripheral
BDNF signaling, including cutaneous derived BDNF, plays in primary afferent hyperexcitability
and pain, including neuropathic pain after SCI. The results obtained here will provide new insight
into the peripheral neurophysiological mechanisms that underlie maladaptive sensory processing
and pain after SCI.

## Key facts

- **NIH application ID:** 9958062
- **Project number:** 1R21NS116665-01
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Sandra M. Garraway
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $425,189
- **Award type:** 1
- **Project period:** 2020-04-01 → 2022-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9958062

## Citation

> US National Institutes of Health, RePORTER application 9958062, Peripheral BDNF drives primary afferent hyperexcitability and pain hypersensitivity (1R21NS116665-01). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/9958062. Licensed CC0.

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