# Astrocytes mediate priming of spinal nociceptive circuits

> **NIH NIH F31** · UNIVERSITY OF CINCINNATI · 2024 · $42,183

## Abstract

PROJECT SUMMARY/ABSTRACT
9% of children born in the United States are admitted to the neonatal intensive care unit where many experience
invasive surgical procedures as part of their medical care. The resulting tissue damage leads to ‘priming’ of the
nociceptive pathway, causing increased pain perception in response to noxious stimuli later in life. Long-term
potentiation (LTP) of sensory synapses onto projection neurons (PN) in the spinal superficial dorsal horn (SDH)
likely contributes to the sensitization of spinal pain circuits by amplifying ascending nociceptive transmission to
the brain. While primary afferent-to-PN synapses typically follow ‘Hebbian’ spike timing dependent plasticity
(STDP), in which presynaptic firing just prior to postsynaptic firing induces LTP, neonatal incision widens the
window of stimulation that induces potentiation, facilitating the amplification of pain transmission. It is becoming
increasingly clear that astrocytes are critical modulators of synaptic transmission, capable of altering the subunit
composition of postsynaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) type glutamate
receptors. However, nothing is known about how astrocyte-synapse communication is involved in the priming of
nociceptive circuits, posing a critical gap in knowledge as insight into astrocytic regulation of plasticity in spinal
PNs will advance our understanding of the molecular basis of STDP, and potentially reveal novel therapeutic
targets to attenuate long-term amplification of nociceptive transmission. The long-term goal is to facilitate
development of chronic pain treatments by advancing our understanding of central nociceptive circuit
development. The short-term goal of this application is to elucidate the role of astrocytes in STDP of sensory
synapses onto SDH PNs involved in the priming of pain pathways after early life injury. Prior studies demonstrate
that neonatal incision persistently increases CP AMPAR expression and relaxes the rules of STDP in PNs.
Recent evidence that astrocytes dynamically inflect plasticity and selectively modulate AMPAR subunit clustering
via secreted factors support the concept that astrocytes are critical for the synaptic changes occurring as a result
of neonatal priming. The central hypothesis is that astrocytes reacting to neonatal surgical incision secrete
factors that recruit Ca2+ permeable (CP) AMPAR, thus fostering an environment permissive to non-Hebbian
LTP at primary afferent-to-PN synapses. This hypothesis will be tested via two aims. Aim 1 will identify the role
of astrocytes in reorganizing postsynaptic glutamate receptor expression after neonatal injury, while Aim 2 will
determine the degree to which astrocytes facilitate LTP in the SDH after early life injury. The proposed research
will identify novel mechanisms by which spinal astrocytes modify glutamate receptor expression and contribute
to the development of persistent changes in activity-dependent potentiation of s...

## Key facts

- **NIH application ID:** 10820761
- **Project number:** 1F31NS135754-01
- **Recipient organization:** UNIVERSITY OF CINCINNATI
- **Principal Investigator:** Judy Joonhi Yoo
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $42,183
- **Award type:** 1
- **Project period:** 2024-01-11 → 2026-01-10

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10820761

## Citation

> US National Institutes of Health, RePORTER application 10820761, Astrocytes mediate priming of spinal nociceptive circuits (1F31NS135754-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10820761. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*