# Cellular mechanisms of antidepressant drug actions in neuropathic pain models

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2022 · $75,171

## Abstract

PROJECT SUMMARY
Neuropathic pain is a chronic condition characterized by sensory, cognitive and affective symptoms. Most of
the drugs used to treat this disorder demonstrate low efficacy and major side-effects. Understanding the
epigenetic and transcriptional mechanisms that modulate the transmission and maintenance of peripheral
nerve injury (PNI) symptoms will be a major step towards the development of novel treatment approaches. Our
earlier findings identified a key role of the epigenetic modifier Histone deacetylase 5 (HDAC5) in the onset of
action and efficacy of antidepressants in models of neuropathic pain. HDAC5 in the Nucleus Accumbens (NAc)
binds to chromatin complexes to suppress the expression of several genes that affect synaptic function,
including the transcription factor MEF2C. The parent R01 proposal investigates the mechanism by which
HDAC5 and downstream targets modulate the actions of antidepressants in the NAc. This supplement project
aims to elucidate cell type-specific epigenetic and transcriptomic mechanisms mediating the antiallodynic
effects of monoamine-targeting antidepressants in models of neuropathic pain. Bioinformatic analysis of single
nuclei RNASeq data will complement findings on HDAC5 and MEF2C actions and will also provide insight on
transcriptomic events associated with antidepressant efficacy. We will validate key findings using fluorescent in
situ hybridization, immunofluorescence, as well as western blot analysis. Pharmacological and genetic models
will be use to test selected genes/intracellular pathways. Understanding the molecular mechanisms mediating
the actions of monoamine-targeting antidepressants will help the development of novel and more efficacious
medications for the treatment of neuropathic pain.

## Key facts

- **NIH application ID:** 10526787
- **Project number:** 3R01NS086444-08S1
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Venetia Zachariou
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $75,171
- **Award type:** 3
- **Project period:** 2022-01-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10526787

## Citation

> US National Institutes of Health, RePORTER application 10526787, Cellular mechanisms of antidepressant drug actions in neuropathic pain models (3R01NS086444-08S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10526787. Licensed CC0.

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