# Cellular and circuitry mechanisms of NRTI-induced pain pathogenesis in the context of opioids and HIV

> **NIH NIH R01** · STATE UNIVERSITY NEW YORK STONY BROOK · 2022 · $569,163

## Abstract

PROJECT SUMMARY
Combination antiretroviral therapy (cART) is the current first-line treatment for human immunodeficiency virus
(HIV) infection. Unfortunately, cART is implicated in various forms of HIV-associated neurological disorders. Pain
is the most common neurological complication that significantly reduces the quality of life of many people living
with HIV (PLWH), and emerging evidence suggests cART critically contributes to the development of pain in
PLWH. However, the mechanism by which cART promotes pain pathogenesis is still incompletely understood
and rationale-based effective adjuvant therapy is not available. In this project, we aim to elucidate the pathogenic
mechanism of nucleoside reverse transcriptase inhibitors (NRTIs), which are the cornerstone antiretroviral drugs
in cART regimens and induce neuropathic pain. Because PLWH on cART are commonly exposed to opioids and
HIV-1 gp120 protein that causes pain, we will also investigate the potential pathogenic interaction between
NRTIs and opioids or gp120. Our data show that separate administration of NRTIs, morphine, or gp120 to mice
causes pathological pain, and that the development of pathological pain induced by these agents shares
mechanistic properties with the activation of glial cells in the spinal dorsal horn. We hypothesize that NRTIs
promote pain pathogenesis in the neural circuit via glial activation and that gp120 and opioids can exacerbate
this condition. We will test this hypothesis by performing: (1) single cell transcriptomic analysis to characterize
the cellular neuropathogenesis induced by NRTIs in conjunction with opioids or gp120 (Aim 1), (2) whole cell
patch recording to characterize the pathologic pain neural circuitry induced by NRTIs with opioids or gp120 (Aim
2), and (3) behavioral testing to characterize pathological pain induced by NRTIs with opioids or gp120 (Aim 3).
Results from this research will help to define the potential detrimental impact of cART on the CNS and its
interactions with HIV and opioids.

## Key facts

- **NIH application ID:** 10559782
- **Project number:** 1R01DA057195-01
- **Recipient organization:** STATE UNIVERSITY NEW YORK STONY BROOK
- **Principal Investigator:** SHAO-JUN TANG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $569,163
- **Award type:** 1
- **Project period:** 2022-09-15 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10559782

## Citation

> US National Institutes of Health, RePORTER application 10559782, Cellular and circuitry mechanisms of NRTI-induced pain pathogenesis in the context of opioids and HIV (1R01DA057195-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10559782. Licensed CC0.

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