# Dorsal horn circuits for mechanical allodynia

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2020 · $516,068

## Abstract

Pain continues to be a major clinical problem due to its high prevalence and lack of adequate treatment
options. The identification of more effective therapies is hampered by a lack of understanding of the neural
circuits and mechanisms that underlie pain. Work outlined in this proposal is focused on delineating the dorsal
horn circuits for mechanical allodynia, a common condition in which touch or movement become painful after
injury. The dorsal horn is a major site for the integration of somatosensory information. It is also where injury-
induced changes in the circuitry give rise to mechanical allodynia. In studies to elucidate the dorsal horn
mechanical allodynia circuits, we have identified populations of dorsal horn excitatory interneurons that
mediate this form of pain. Additionally, we present evidence supporting the concept that the neural circuitry that
mediates mechanical allodynia in the dorsal horn differs depending on the nature of the injury. Thus, the
overarching goal of this project is to delineate the dorsal horn circuits underlying mechanical allodynia in the
context of the type of injury, inflammatory and neuropathic. In Aim 1) we will determine whether the
populations of excitatory interneurons are required for mechanical allodynia produced by models of
inflammatory and neuropathic pain. In Aim 2) we will expand our understanding of the dorsal horn circuitry
related to these excitatory interneuron populations under naïve conditions by identifying the neurons
monosynaptically connected to them. This more detailed picture of the basic dorsal horn circuitry will facilitate
experiments aimed at identifying key changes that underlie mechanical allodynia caused by different types of
injuries. In Aim 3) we will use an in vitro model of mechanical allodynia to test the role of these excitatory
interneuron populations in inflammatory and neuropathic pain models. This will allow us to assess on a
synaptic level the role of these neurons in mechanical allodynia in the context of injury-type. Classes of
afferents and populations of lamina I projection neurons will also be assessed. These novel studies will provide
a critical anatomical framework with which to advance molecular- and synaptic-level studies of the neurons and
mechanisms that underlie mechanical allodynia as well as generate new therapeutic strategies.

## Key facts

- **NIH application ID:** 9977288
- **Project number:** 5R01NS107364-02
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** REBECCA P SEAL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $516,068
- **Award type:** 5
- **Project period:** 2019-06-15 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9977288

## Citation

> US National Institutes of Health, RePORTER application 9977288, Dorsal horn circuits for mechanical allodynia (5R01NS107364-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9977288. Licensed CC0.

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