# Developmental Regulation of Intrinsic Excitability in Spinal Pain Networks

> **NIH NIH R01** · UNIVERSITY OF CINCINNATI · 2020 · $345,625

## Abstract

Project Summary/Abstract
 Despite the high prevalence of pediatric pain, most commonly seen as musculoskeletal pain, little is
known about how the immature CNS processes distinct types of noxious sensory information. In particular, the
mechanisms regulating the ascending flow of nociceptive signals from the spinal cord to the brain during early
life remain unclear. Since lamina I projection neurons represent an essential output of the spinal nociceptive
circuit and are critical for the generation of chronic pain, a better understanding of the ionic conductances
which control the intrinsic membrane excitability of these neurons during early life, and how the firing of this
population shapes the maturation of synaptic inputs from different classes of sensory afferents, represents an
important step towards addressing this issue. The long-term goal is to facilitate the design of evidence-based
approaches to treat pediatric pain by advancing the knowledge of the developmental neurobiology of central
nociceptive networks. The overall objective of this application is to identify the key factors regulating the firing
of ascending projection neurons during early life and to determine the role of this activity in modulating primary
afferent synapses onto these cells. The central hypothesis is that classic inward-rectifying K+ (Kir2) and
NALCN Na+ leak channels jointly regulate action potential discharge in neonatal projection neurons and
thereby influence the postnatal development of functionally distinct synaptic inputs from cutaneous and muscle
sensory afferents. The rationale of the proposed research is that understanding the intrinsic and synaptic
mechanisms that dictate the excitability of immature projection neurons (PNs) is the first step towards
controlling the signaling “gain” of developing spinal nociceptive circuits, which would facilitate the design of
novel strategies to alleviate pediatric pain. 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) Identify
the ion channels shaping the intrinsic membrane excitability of ascending spinal PNs during early life; (2)
Elucidate the properties of cutaneous and muscle afferent synapses onto developing PNs; and (3) Determine
the extent to which the intrinsic membrane excitability of developing PNs influences the maturation of primary
afferent synaptic inputs. These aims will be accomplished by using a multidisciplinary experimental approach
that includes in vitro electrophysiological, genetic and immunohistochemical techniques. The outcome of these
investigations will be the first identification of which voltage-independent (i.e. “leak”) ion channels shape the
intrinsic membrane excitability of neonatal spinal projection neurons, as well as the establishment of a
functional relationship between the firing of these cells and the maturation of synaptic inputs from skin and
muscle affer...

## Key facts

- **NIH application ID:** 9936454
- **Project number:** 5R01NS072202-10
- **Recipient organization:** UNIVERSITY OF CINCINNATI
- **Principal Investigator:** Mark L Baccei
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $345,625
- **Award type:** 5
- **Project period:** 2010-09-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9936454

## Citation

> US National Institutes of Health, RePORTER application 9936454, Developmental Regulation of Intrinsic Excitability in Spinal Pain Networks (5R01NS072202-10). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9936454. Licensed CC0.

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