# Sensitization of developing sensory neurons after incision

> **NIH NIH R01** · CINCINNATI CHILDRENS HOSP MED CTR · 2020 · $410,648

## Abstract

ABSTRACT: Approximately 15-20% of children experience persistent or chronic pain. However, compared to
adults, we know relatively little about the mechanisms of pediatric pain development. A basic understanding of
nociceptive processing in the immature nervous system is therefore crucial in order to develop more
appropriate treatments for pain in children. Patients with growth hormone deficiency (GHD) may provide insight
into this clinical problem. Patients with GHD often display pain at rest in addition to deficits in growth.
Moreover, treatment of certain pain patients with GH provides analgesia. We have found that cutaneous
inflammation and muscle incision in mice reduces GH in the injured tissues. Observed changes in gene
expression, afferent function and pain-related behaviors during neonatal injury are blocked by treating mice
with exogenous GH. New pilot data suggests that macrophage dependent sequestering of GH at the site of
peripheral injury, subsequently reduces inhibitory microRNA expression (e.g. miR-133a) within nociceptors to
increase transcription factor (e.g. serum response factor (SRF)) dependent upregulation of various receptors
and channels that modulate afferent function and pain-related beahviors. The main goal of this proposal is to
determine the molecular mechanisms of how GH levels regulate sensory neuron sensitization during muscle
incision and how this may underlie acute and persistent neonatal hypersensitivity. Specific Aim 1 will use a
novel ex vivo somatosensory recording preparations to determine the effects of macrophage or sensory
neuron specific knockout of the GH receptor on the sensitization of sensory neurons in uninjured neonatal mice
or animals with muscle incision. Specific Aim 2 will test whether knockdown of a transcription factor (SRF) or
overexpression of a microRNA (miR-133a), that is thought to regulate receptor expression in neurons (and
thereby modulate peripheral sensitization), modifies these same changes in afferent function after muscle
incision using in vivo siRNA-mediated knockdown or plasmid based overexpression strategies in single
peripheral nerves in conjunction with ex vivo recording. Each of these two aims will be complemented by
analysis of ongoing and evoked hypersensitivity. Finally, Specific Aim 3 will use behavioral analyses and/or ex
vivo recording to determine the influence of localized GH treatments, GHr KO, SRF inhibition or miR-133a
overexpression in neonatally incised mice on the prolonged effects to subsequent adolescent incision. These
experiments will allow a better understanding of the unique mechanisms in primary sensory neurons by which
peripheral GH levels regulate afferent sensitization and neonatal pain development. These studies will facilitate
understanding of the transition from acute to chronic pediatric pain, and will allow us to determine the utility of
GH as a pain therapy for children. This work may also lead to the design of more suitable treatments for
pedia...

## Key facts

- **NIH application ID:** 9937849
- **Project number:** 5R01NS105715-02
- **Recipient organization:** CINCINNATI CHILDRENS HOSP MED CTR
- **Principal Investigator:** Michael P Jankowski
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $410,648
- **Award type:** 5
- **Project period:** 2019-06-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9937849

## Citation

> US National Institutes of Health, RePORTER application 9937849, Sensitization of developing sensory neurons after incision (5R01NS105715-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9937849. Licensed CC0.

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