# Neuroimmune interactions regulating the balance between remission and relapse of pain

> **NIH NIH R01** · MICHIGAN STATE UNIVERSITY · 2022 · $416,995

## Abstract

Persistent pain is common and debilitating. Long after apparent remission of the pain initiated by
the primary insult, some patients experience relapse and recurrent episodes of severe pain. The
long-term goal of this project is to decipher mechanisms that regulate the balance between
remission and relapse of pain. Understanding these mechanisms will help to identify new
therapeutic strategies to prevent the transition from acute to chronic pain and reduce the use of
opioid for treatment of pain. We have developed a new mouse model to study the remission and
relapse of pain. After a primary insult (surgical incision or a short dose of chemotherapy), a short
period of pain (acute pain) is followed by remission in which pain sensitivity is absent. However,
during remission pain can be reinstated by inhibition of anti-inflammatory cytokine or opioid
receptor signaling, neither of which affect pain sensitivity in naive animals. Our preliminary data
show that interleukin (IL)-10 is permanently upregulated during remission from pain and keeps
neuroinflammation silent and upregulates δ-opioid receptor (δOR) gene expression and analgesic
effects.
This suggests that remission is a sensitized state that results from long-term neuroplasticity in
the nociceptive system, which if inhibited will trigger relapse of pain. Our long-term goal is to
switch transient remission to permanent recovery. Towards this goal, the central hypothesis of
our proposal is that persistent IL-10 signaling is necessary to prevent the relapse to pain by
keeping neuroinflammation silent and facilitating the activation of the endogenous opioid
system. Thus, we will test this hypothesis with 2 specific aims. Our first aim will test the
hypothesis that IL-10 signaling acts as a “brake” to keep neuroinflammation latent and prevents
relapse to pain. Our second aim will investigate the hypothesis that relapse is prevented
because IL-10 signaling promotes upregulation of gene expression and functional activation of
δOR in the DRG. This proposal will fill critical gaps of knowledge on the roles of neuroimmune
and immune-opioid crosstalk in chronic pain.
Because regulation of the remission and relapse of pain has not been investigated previously,
our model of pain recurrence can transform our knowledge on long lasting nociceptive plasticity
in chronic pain. Ultimately, it could transform clinical practices by treating patients in remission
to prevent the relapse of pain.

## Key facts

- **NIH application ID:** 10427200
- **Project number:** 5R01NS121259-02
- **Recipient organization:** MICHIGAN STATE UNIVERSITY
- **Principal Investigator:** Geoffroy O Laumet
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $416,995
- **Award type:** 5
- **Project period:** 2021-06-15 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10427200

## Citation

> US National Institutes of Health, RePORTER application 10427200, Neuroimmune interactions regulating the balance between remission and relapse of pain (5R01NS121259-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10427200. Licensed CC0.

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