# Targeting GPR109A for the treatment of pain in systemic lupuc erythematosus

> **NIH NIH R01** · MERCER UNIVERSITY MACON · 2020 · $337,356

## Abstract

Chronic pain in systemic lupus erythematosus (SLE) significantly impairs the quality of life and productivity of
patients due to the lack of potent and safe painkillers. There is a highly unmet need for the development of
novel analgesics. Surprisingly, no animal studies had been reported about the mechanisms underlying
chronic pain in SLE until our recent study. We found that activation of microglial macrophage colony-
stimulating factor-1 (M-CSF1) receptors and over-production of IL-1β in the spinal dorsal horn play a crucial
role in the enhancement of spinal excitatory glutamatergic synaptic transmission and generation of chronic
pain in a lupus mouse model, MRL lupus prone (MRL/lpr) mice. Our study demonstrated that controlling the
spinal neuroinflammation is an effective approach for the treatment of pain in lupus. GPR109A was newly
identified in different immune cell types and its activation produces anti-inflammatory effects. Whether and
how spinal GPR109A regulates spinal neuroinflammation and the genesis of pathological pain (including
chronic pain in SLE) is unknown. Our overarching hypothesis is that activation of the anti-inflammatory
receptor GPR109A in spinal microglia attenuates SLE-induced chronic pain and microglial production of pro-
inflammatory mediators, in part, through suppressing microglial N-type calcium channel activity. This
hypothesis will be tested in 3 specific aims using a well-established mouse model of human SLE, MRL/lpr
lupus-prone mice: 1. To test the hypothesis that chronic pain in MRL/lpr mice is reduced by activation of
spinal GPR109A; 2. Test the hypothesis that calcium channels are open (activated) in spinal microglia of
MRL/lpr mice with chronic pain, and activation of GPR109A suppresses microglial N-type Ca2+ channel
activity in MRL/lpr mice with chronic pain; 3. To test the hypothesis that microglial activation and production of
pro-inflammatory mediators are regulated by N-type Ca2+ channels and GPR109A. We will apply
multidisciplinary cutting edge techniques (including molecular biology, cell culture, genetics, pharmacology,
ex-vivo patch-clamp recording, and behavioral assessments) to reach these aims. This study is the first to
uncover analgesic effects of the GPR109A activator and its underlying mechanisms. As GPR109A agonists
have been in clinical trials for the treatment of dyslipidemia, completion of this project will result in a novel
therapeutic use of these drugs, and a faster, cheaper, and less risky development of analgesics, which has
high potential for “fast-track” clinical approval for their use in patients. Given that spinal neuroinflammation is
a common feature shared by many chronic pain conditions, the results collected in the study may also
provide a base for the use of GRP109A agonists for the treatment of other chronic pain conditions.

## Key facts

- **NIH application ID:** 9939694
- **Project number:** 5R01NS107569-04
- **Recipient organization:** MERCER UNIVERSITY MACON
- **Principal Investigator:** Han-Rong Weng
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $337,356
- **Award type:** 5
- **Project period:** 2018-10-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9939694

## Citation

> US National Institutes of Health, RePORTER application 9939694, Targeting GPR109A for the treatment of pain in systemic lupuc erythematosus (5R01NS107569-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9939694. Licensed CC0.

---

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