# Examining the roles A-delta LTMRs and BDNF signaling play in neuropathic pain after SCI

> **NIH NIH R01** · EMORY UNIVERSITY · 2021 · $386,582

## Abstract

Project Summary/Abstract
We propose that afferent plasticity at their peripheral and central terminals plays a critical role in chronic
neuropathic pain, expressed as allodynia, after SCI. A-LTMRs, a group of small diameter myelinated afferents
that innervate the hairy skin, have recently been shown to signal directionality of touch. They can be identified
by their expression of the BDNF receptor, TrkB. A-LTMRs require BDNF-TrkB signaling for normal
mechanosensory functions. BDNF and TrkB are implicated in many adaptive and maladaptive processes,
including pain. However, it is not clear what role they play in neuropathic pain after SCI.
We hypothesize that maintained maladaptive peripheral plasticity involving BDNF-TrkB signaling produces
hyperexcitability of A-LTMRs, in turn lead to at-level pain after SCI. In fact, we propose that SCI transforms
A-LTMRs into allodynia-encoding nociceptors in dermatomes adjacent to the injury and that this
transformation is in part due to the immense spatial and temporal plasticity SCI imposes on BDNF-TrkB
signaling. The proposed study consisting of 3 specific aims will be done in transgenic mice which will enable us
to selectively target TrkB-expressing A-LTMRs, in intact subjects and after T10 moderate to severe contusion
SCI.
In SA 1, electrophysiological studies using the ex-vivo skin-nerve, in-vitro adult mouse model and spinal slices
with attached dorsal roots in TrkB::ChR2 mice will assess SCI effects on A-LTMRs recruitment, firing and
synaptic responses. We will also examine SCI-induced expansion A-LTMRs’ receptive field, as a potential
outcome of peripheral afferent sprouting (SA 2). SA 2 will examine anatomical and neurochemical plasticity of
A-LTMRs, and changes in BDNF and TrkB expression in the spinal cord, skin and DRG. SA 3 will employ
behavioral tests to investigate A-LTMRs’ role in the development of at-level mechanical allodynia after SCI
using modified place escape/aversion paradigms, and measures of audible and ultrasonic vocalizations
following mechanical and optical stimulation. We will also incorporate novel ultrasensitive movement detection
sensors for continuous monitoring of respiratory rates, which is a measurable index of sympathetic arousal that
may also be indicative of pain.
This innovative and clinically-relevant study will be the first to identify A-LTMR plasticity as a neural
mechanism of at-level mechanical allodynia after SCI and that peripheral plasticity mediates the transformation
of cutaneous touch afferent into nociceptors. The results obtained from this study will increase our knowledge
of the neurophysiological mechanisms that underlie maladaptive sensory processing and pain after SCI.

## Key facts

- **NIH application ID:** 10200158
- **Project number:** 5R01NS102850-04
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Sandra M. Garraway
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $386,582
- **Award type:** 5
- **Project period:** 2018-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10200158

## Citation

> US National Institutes of Health, RePORTER application 10200158, Examining the roles A-delta LTMRs and BDNF signaling play in neuropathic pain after SCI (5R01NS102850-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10200158. Licensed CC0.

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