# Lipid signaling in supraspinal pain pathways

> **NIH NIH R01** · INDIANA UNIVERSITY INDIANAPOLIS · 2021 · $457,701

## Abstract

PROJECT SUMMARY
Neurons in the central amygdala (CeA) contribute to pain modulation. However, their contribution to the sensory-
discriminative and/or emotional-affective dimensions of chronic pain, nor their neurochemical modulation, are
understood. Our preliminary data using slice recordings and behavior provide a compelling premise for the idea
that drugs targeting the receptors for the bioactive lysophospholipid, sphingosine-1-phosphate (S1P) act within
the CeA to inhibit inflammatory and neuropathic pain. This sets the stage for our long-term goal to understand
how lipid signaling controls the supraspinal control of acute and chronic pain. The objectives of this proposal are
to: determine neurophysiological changes to molecular specific CeA neurons in multiple models of pain (Aim 1),
elucidate the effects of S1P signaling on the intrinsic and synaptic excitability of defined subpopulations of CeA
neurons (Aim 2), and determine if S1PR agonism in the CeA is analgesic in models of inflammatory and
neuropathic pain (Aim 3). In Aim 1, we use transgenic mouse lines, electrophysiology, and optogenetics to test
the hypotheses that tissue or nerve injury reduces excitability of specific subclasses of CeA neurons based on
their molecular profile. In Aim 2, we test the hypotheses that activation of S1P signaling increases the excitability
and synaptic connectivity within a population of molecularly distinct CeA neurons. In Aim 3, we use intracranial
drug infusions and chemogenetics to test the hypothesis that activation of S1P receptors in the CeA attenuates
inflammatory and neuropathic pain via a specific subtype of CeA neuron. Experimental support of these concepts
will facilitate the development of existing (e.g. FDA-approved fingolimod) and novel S1PR compounds for the
treatment of chronic pain.

## Key facts

- **NIH application ID:** 10130013
- **Project number:** 5R01NS112632-02
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Patrick L Sheets
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $457,701
- **Award type:** 5
- **Project period:** 2020-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10130013

## Citation

> US National Institutes of Health, RePORTER application 10130013, Lipid signaling in supraspinal pain pathways (5R01NS112632-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10130013. Licensed CC0.

---

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