Microparticles Mediate Lipopolysaccharide-induced Inflammation and Chronic Pain in Mouse Model

Recent evidence highlights microparticles (MPs) as crucial players in intercellular communication among immune cells, yet their role in inflammation-induced chronic pain remains unexplored. In this study, we investigated the involvement of MPs in the progression of inflammation and associated pain using mouse models of chronic neuroinflammation induced by repeated intraperitoneal injections of lipopolysaccharide (LPS; 1 mg/kg for four consecutive days) in C57BL/6 mice. Chronic pain was analyzed at baseline (day 0) and on day 21 post-LPS injection using von Frey and the hot metal plate tests. We found a significant increase in the levels of proinflammatory mediators and activation of the TLR4-NF kappa B signaling pathways following LPS administration. Additionally, transcriptional upregulation of chronic pain-associated TRP channels and glutamate receptors, including TRPA1, TRPM2, and mGluR2 in the cortex and hippocampus as well as mGluR5 in the cortex, was noted on day 21 post-LPS injection. Moreover, upregulation of TRPM2, mGluR2, and mGluR5 was found in the spinal cord, along with increased TRPA1 protein expression in the brain cortex. Plasma-derived MPs were isolated, revealing a significant increase in concentration 21 days after LPS injection, accompanied by TNF-alpha DNA encapsulation and increased TNF-alpha mRNA expression within MPs. Furthermore, MPs concentration positively correlated with the expression of TRPA1, TRPM2, mGluR2, and mGluR5. These findings suggest that MPs contribute to inflammation-induced chronic pain, highlighting their potential as therapeutic targets.