Upregulation of Delta Opioid Receptor by Meningeal Interleukin-10 Prevents Relapsing Pain

Authors

Kufreobong E Inyang
Jaewon Sim
Kimberly B Clark
Matan Geron
Karli Monahan
Christine Evans
Patrick O'Connell
Sophie Laumet
Bo Peng
Jiacheng Ma
Cobi J Heijnen
Robert Dantzer
Grégory Scherrer
Annemieke Kavelaars
Matthew Bernard
Yasser A Aldhamen
Joseph K Folger
Alexis Bavencoffe
Geoffroy Laumet

Language

English

Publication Date

1-1-2025

Journal

Brain, Behavior, and Immunity

DOI

10.1016/j.bbi.2024.09.031

PMID

39349285

PMCID

PMC11624093

PubMedCentral® Posted Date

1-1-2026

PubMedCentral® Full Text Version

Author MSS

Abstract

Chronic pain often includes periods of transient amelioration and even remission that alternate with severe relapsing pain. While most research on chronic pain has focused on pain development and maintenance, there is a critical unmet need to better understand the mechanisms that underlie pain remission and relapse. We found that interleukin (IL)-10, a pain resolving cytokine, is produced by resident macrophages in the spinal meninges during remission from pain and signaled to IL-10 receptor-expressing sensory neurons. Using unbiased RNA-sequencing, we identified that IL-10 upregulated expression and antinociceptive activity of δ-opioid receptor (δOR) in the dorsal root ganglion. Genetic or pharmacological inhibition of either IL-10 signaling or δOR triggered relapsing pain. Overall, our findings, from electrophysiology, genetic manipulation, flow cytometry, pharmacology, and behavioral approaches, indicate that remission of pain is not simply a return to the naïve state. Instead, remission is an adapted homeostatic state associated with lasting pain vulnerability resulting from persisting neuroimmune interactions within the nociceptive system. Broadly, this sheds light on the elusive mechanisms underlying recurrence a common aspect across various chronic pain conditions.

Keywords

Animals, Interleukin-10, Receptors, Opioid, delta, Meninges, Mice, Ganglia, Spinal, Up-Regulation, Male, Mice, Inbred C57BL, Recurrence, Chronic Pain, Macrophages, Sensory Receptor Cells, Receptors, Interleukin-10

Published Open-Access

yes

Recommended Citation

Inyang, Kufreobong E; Sim, Jaewon; Clark, Kimberly B; et al., "Upregulation of Delta Opioid Receptor by Meningeal Interleukin-10 Prevents Relapsing Pain" (2025). Faculty, Staff and Student Publications. 5337.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/5337