# Pathogenic mechanisms of HIV-associated pain

> **NIH NIH R01** · UNIVERSITY OF TEXAS MED BR GALVESTON · 2021 · $577,629

## Abstract

PROJECT SUMMARY
Pain is the most common and most costly neurological disorder in HIV-1/AIDS patients, yet current pain
treatment provides only symptomatic management that is often ineffective. Lack of deep, mechanistic
understanding of the underlying mechanism of HIV-associated pain has significantly impeded the development
of needed effective, rationale-based approaches for pain control in HIV patients. Emerging evidence suggests
a crucial role for neuron-astrocyte interactions in the spinal dorsal horn (SDH; the pain processing center in the
spinal cord) in the pathogenesis of HIV-associated pain. However, the mechanism that mediates these
intercellular interactions is largely unknown. Our work prior and preliminary studies suggest that gp120 elicits
exosome-based signals to mediate bidirectional neuron-astrocyte communication in the SDH. Importantly, the
exosome pathway is up-regulated in the SDH of the HIV patients with pathological pain. Pharmacological
inhibition of exosome secretion in the SDH blocks the expression of gp120-induced pain. We propose that
exosome-mediated neuron-astrocyte interactions play a critical role in gp120-induced pain pathogenesis.
Specifically, we hypothesize that gp120 stimulates exosome-based secretion of Wnt signaling protein from
SDH neurons, which then stimulates astrocytes to release exosomes that in return feedback to SDH pain
processing neurons to promote central sensitization. We will use an interdisciplinary approach of conditional
knockout, mosaic analysis, patch clamp recording and behavioral analysis to test this hypothesis. The
mechanistic insights gained from this project will facilitate the development of novel therapies for HIV-
associated pain targeting this underlying exosome-mediated pathogenic process.

## Key facts

- **NIH application ID:** 10237218
- **Project number:** 5R01NS079166-10
- **Recipient organization:** UNIVERSITY OF TEXAS MED BR GALVESTON
- **Principal Investigator:** SHAO-JUN TANG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $577,629
- **Award type:** 5
- **Project period:** 2012-09-01 → 2021-09-02

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10237218

## Citation

> US National Institutes of Health, RePORTER application 10237218, Pathogenic mechanisms of HIV-associated pain (5R01NS079166-10). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10237218. Licensed CC0.

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