IL-10/β-Endorphin-Mediated Neuroimmune Modulation on Microglia during Antinociception

Microglia are glial cells centrally related to pathophysiology and neuroimmunological regulation of pain through microglia-neuron crosstalk mechanisms. In contrast, anti-inflammatory mechanisms guided by immunological effectors such as IL-10 trigger the secretion of analgesic substances, culminating in the differential expression of genes encoding endogenous opioid peptides, especially beta-endorphin. Thus, when fi-endorphin binds to the mu-opioid receptor, it generates neuronal hyperpolarization, inhibiting nociceptive stimuli. This review aimed to summarize the recent advances in understanding the mechanism by which IL-10/ beta-endorphin can reduce pain. For this, databases were searched for articles from their inception up until November 2022. Two independent reviewers extracted the data and assessed the methodological quality of the included studies, and seventeen studies were considered eligible for this review. Several studies have demonstrated the impact of IL-10/beta-endorphin in reducing pain, where IL-10 can stimulate GLP-1R, GRP40, and alpha 7nAChR receptors, as well as intracellular signaling pathways, such as STAT3, resulting in increased beta-endorphin expression and secretion. In addition, molecules such as gabapentinoids, thalidomide, cynandione A, morroniside, lemairamin, and cinobufagin, as well as non-pharmacological treatments such as electroacupuncture, reduce pain through IL-10 mediated mechanisms, reflecting a microglia-dependent fi-endorphin differential increase. This process represents a cornerstone in pain neuroimmunology knowledge, and the results obtained by different studies about the theme are presented in this review.

Automated summary

This review summarizes recent advances in understanding the mechanism by which IL-10/β-endorphin can reduce pain. Studies have demonstrated that IL-10 can stimulate receptors and signaling pathways, resulting in increased β-endorphin expression and secretion. Additionally, certain drugs and non-pharmacological treatments reduce pain through IL-10 mediated mechanisms, highlighting the importance of this process in pain neuroimmunology.