# Synaptic Function within Mature Central Pain Networks after Neonatal Injury

> **NIH NIH R01** · UNIVERSITY OF CINCINNATI · 2022 · $362,882

## Abstract

Despite growing evidence that tissue damage during a critical period of early life can exacerbate pain
severity following subsequent injury, the cellular and molecular mechanisms by which neonatal trauma can
‘prime’ developing nociceptive pathways remain unclear. Furthermore, while inhibitory interneurons in the adult
spinal dorsal horn (DH) are known to be comprised of multiple subpopulations which regulate distinct aspects
of sensory processing, the classes of inhibitory interneurons that are important for shaping pain sensitivity in
the neonate have yet to be identified. Finally, the degree to which neonatal injury primes developing pain
circuits by disrupting the maturation of specific subpopulations of inhibitory DH neurons necessary for
feedforward inhibition of ascending spinal projection neurons has yet to be elucidated. The long-term goal is to
facilitate the design of age-appropriate strategies to treat chronic pain by advancing our understanding of the
developmental neurobiology of central nociceptive networks. The objective of this application is to elucidate
the consequences of early tissue injury for the maturation of identified inhibitory synaptic circuits within the
spinal DH. The central hypothesis is that neonatal tissue damage disrupts the development of primary afferent
drive to dynorphin-expressing (DYN) interneurons mediating feedforward inhibition of ascending projection
neurons, which contributes to the priming of spinal nociceptive circuits to subsequent injury. The rationale of
the proposed research is that by yielding novel insight into the postnatal development of distinct spinal
inhibitory circuits under normal and pathological conditions, these studies will lay a conceptual foundation for
new therapeutic approaches to restrict the output of the spinal pain network in an age-specific manner and
minimize the adverse long-term effects of neonatal injury on the developing CNS. Guided by strong
preliminary data, the central hypothesis will be tested and the overall objective of this application achieved by
pursuing the following specific aims: (1) Determine how early tissue damage shapes primary afferent drive to
inhibitory interneurons in the developing DH; (2) Identify the DH interneurons which mediate feedforward
inhibition of developing spinal projection neurons under normal and pathological conditions; and (3) Identify the
inhibitory interneurons in the developing DH whose ability to suppress pain is compromised by neonatal tissue
injury. These aims will be accomplished by using a multidisciplinary experimental approach that includes in
vitro electrophysiological, optogenetic, chemogenetic, behavioral and immunohistochemical techniques. The
outcome of these investigations will be the first insight into how early tissue damage alters the functional
organization of inhibitory microcircuits in the developing spinal nociceptive network and thereby diminishes
their ability to suppress pain sensation. As a result, the prop...

## Key facts

- **NIH application ID:** 10343830
- **Project number:** 5R01NS080889-09
- **Recipient organization:** UNIVERSITY OF CINCINNATI
- **Principal Investigator:** Mark L Baccei
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $362,882
- **Award type:** 5
- **Project period:** 2013-09-21 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10343830

## Citation

> US National Institutes of Health, RePORTER application 10343830, Synaptic Function within Mature Central Pain Networks after Neonatal Injury (5R01NS080889-09). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10343830. Licensed CC0.

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