# Identification of the specific low-threshold primary afferents that elicit aversive behavior after neuropathic injury in mice

> **NIH NIH F31** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 · $37,080

## Abstract

Project Summary/Abstract
Up to 10% of the global population is affected by neuropathic pain caused by lesions or disease to the
somatosensory nervous system. A common symptom of neuropathic pain is dynamic mechanical allodynia, a
condition in which light brushing of the skin is perceived as extremely painful. Many patients that suffer from
mechanical allodynia do not respond to current treatments. In neuropathic patients, it is well-established that the
activation of myelinated low-threshold primary afferents is required for mechanical allodynia. However, there
is significant diversity in these afferents and the specific primary afferent subtypes involved in driving allodynia
are unknown. It has also been shown that lamina 1 spinal projection neurons, which receive input from primary
afferents and project to the brain, become sensitized to mechanical stimuli after neuropathic injury and are
thought to be involved in mediating allodynia. Therefore, I hypothesize that the activation of specific low-
threshold mechanoreceptive primary afferent subtypes provide greater input to lamina 1 spinal
projection neurons and cause aversion in mice after neuropathic injury. In Aim 1, in naïve and neuropathic
mice, I propose to use a spinal cord-nerve-skin ex-vivo preparation to activate specific subtypes of low-threshold
primary afferent using optogenetics while recording from back-labeled lamina 1 spinal projection neurons. In
these initial studies, I will examine three different low-threshold afferent subtypes that respond well to light
brushing of the skin, including Aδ low-threshold afferents, Aβ rapidly adapting afferents with lanceolate endings,
and Aβ afferents with circumferential endings. As a potential electrophysiological basis for allodynia, the results
will determine which subtypes of low-threshold primary afferents give greater input to lamina 1 spinal projection
neurons after neuropathic injury. In Aim 2, in a behavioral model, I will employ an LED-lit place aversion
experiment to activate specific low-threshold afferents using optogenetics in naïve and neuropathic mice. Here,
the results will determine which low-threshold primary afferents contribute to aversive behavior after neuropathic
injury. In conclusion, it has been shown that blocking all low-threshold primary afferents alleviates mechanical
allodynia in patients, but the specific subtypes of afferents involved in allodynia are not known. This knowledge
may lead to therapeutics that block allodynia at its source while maintaining the majority of cutaneous sensory
afferents.

## Key facts

- **NIH application ID:** 10178131
- **Project number:** 5F31NS111793-03
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Joseph J Salsovic
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $37,080
- **Award type:** 5
- **Project period:** 2019-05-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10178131

## Citation

> US National Institutes of Health, RePORTER application 10178131, Identification of the specific low-threshold primary afferents that elicit aversive behavior after neuropathic injury in mice (5F31NS111793-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10178131. Licensed CC0.

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