# A Female Specific Role of RGSz1 in Modulation of Chronic Pain

> **NIH NIH R01** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2022 · $175,065

## Abstract

SUMMARY
While the mechanisms modulating the transmission and perception of chronic pain differ
between men and women, the exact neuroanatomical and molecular differences existing
between the sexes remain only partly understood. This proposal focuses on the study of
intracellular mechanisms that modulate symptoms of long-term pain states in female mice. We
have identified signal transduction mechanisms in the mouse ventrolateral periaqueductal gray
(vlPAG) that selectively modulate sensory symptoms of inflammatory and neuropathic pain in
female mice. The signal transduction modulator Regulator of G Protein Signaling-1 (RGSz1)
controls the function of G protein coupled receptors (GPCRs) by binding to activated Gi
subunits, including the Golgi enriched Gz. RGSz1 negatively modulates the amplitude and
direction of signal transduction of several GPCRs involved in the modulation of pain processing,
including the serotonin 5HT1A receptor. We recently found that RGSz1 mRNA and protein
levels are dynamically regulated in the vlPAG of female (but not male) mice by long-term
peripheral inflammation. Constitutive deletion of the RGSz1 gene or vlPAG-specific knockdown
of RGSz1, exacerbate sensory hypersensitivity behaviors such as thermal hyperalgesia and
mechanical allodynia in female mice, but they have no effect in male mice. We will investigate
the mechanisms regulating the expression of RGSz1 in the male and female vlPAG at various
points after the induction of peripheral nerve injury or inflammation. We will apply several
genetic mouse models for regional inactivation or overexpression of RGSz1 in vlPAG neuronal
subsets, along with brain biochemistry, electrophysiology and voltammetry to understand the
sex-specific role of RGSz1 in the function of the descending inhibitory pathway in models of
chronic pain. Since RGSz1 plays a prominent role in the function of the Golgi apparatus, will
apply chronic pain models to understand the impact of RGSz1 on the expression levels of trans-
Golgi components in the presence and in the absence of pain. Finally, we will use RNA
Sequencing to understand the impact of RGSz1 on gene expression adaptations underlying
chronic pain states.

## Key facts

- **NIH application ID:** 10834544
- **Project number:** 7R01NS111351-04
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** Venetia Zachariou
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $175,065
- **Award type:** 7
- **Project period:** 2020-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10834544

## Citation

> US National Institutes of Health, RePORTER application 10834544, A Female Specific Role of RGSz1 in Modulation of Chronic Pain (7R01NS111351-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10834544. Licensed CC0.

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