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. 2024 Nov 25;26(1):48.
doi: 10.1007/s12017-024-08809-x.

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

Anjali Singh  1 , Khushi  1 , Vinod Tiwari  2 , Alok Kumar  3
Affiliations

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

Anjali Singh et al. Neuromolecular Med. .

Abstract

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-NFκB 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-α DNA encapsulation and increased TNF-α 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.

Keywords: Chronic pain; Inflammation; Lipopolysaccharides; Microparticles; TRP channels; mGluRs.

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Conflict of interest statement

Declarations. Competing Interest: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Ethical Approval: Power calculations were conducted using PASS (Hintze, J. Number Cruncher Statistical System, Kaysville, Utah, 2001) to determine the optimal number of animals needed for the study. All animal procedures and experiments were ethically approved and performed in accordance with the institutional guidelines of SGPGIMS (IAEC/P-26/2019).

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