Interleukin-1beta and Inflammasome Expression in Spinal Cord Following Chronic Constriction Injury in Male and Female Rats

Authors

Suzanne M Green-Fulgham
Jayson B Ball
Andrew J Kwilasz
Michael E Harland
Matthew G Frank
Joseph M Dragavon
Peter M Grace
Linda R Watkins

Publication Date

1-1-2024

Journal

Brain Behavior Immunology

Abstract

Females represent a majority of chronic pain patients and show greater inflammatory immune responses in human chronic pain patient populations as well as in animal models of neuropathic pain. Recent discoveries in chronic pain research have revealed sex differences in inflammatory signaling, a key component of sensory pathology in chronic neuropathic pain, inviting more research into the nuances of these sex differences. Here we use the chronic constriction injury (CCI) model to explore similarities and differences in expression and production of Inflammatory cytokine IL-1beta in the lumbar spinal cord, as well as its role in chronic pain. We have discovered that intrathecal IL-1 receptor antagonist reverses established pain in both sexes, and increased gene expression of inflammasome NLRP3 is specific to microglia and astrocytes rather than neurons, while IL-1beta is specific to microglia in both sexes. We report several sex differences in the expression level of the genes coding for IL-1beta, as well as the four inflammasomes responsible for IL-1beta release: NLRP3, AIM2, NLRP1, and NLRC4 in the spinal cord. Total mRNA, but not protein expression of IL-1beta is greater in females than males after CCI. Also, while CCI increases all four inflammasomes in both sexes, there are sex differences in relative levels of inflammasome expression. NLRP3 and AIM2 are more highly expressed in females, whereas NLRP1 expression is greater in males.

Keywords

Animals, Female, Humans, Male, Rats, Chronic Pain, Constriction, DNA-Binding Proteins, Inflammasomes, Interleukin-1beta, Neuralgia, NLR Family, Pyrin Domain-Containing 3 Protein, Spinal Cord, sex difference, sciatic nerve, neuropathic pain, spinal cord, NLRP3, AIM2, NLRP1, NLRC4, rats, interleukin-1 receptor antagonist

DOI

10.1016/j.bbi.2023.10.004

PMID

37838078

PMCID

PMC10841465

PubMedCentral® Posted Date

1-1-2025

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes