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Addressing Meta-Inflammation in the Comprehensive Management of Chronic Pain

McMasters M, Mora J

Cureus, 2025

5 citations

Abstract

Chronic pain is a widespread condition affecting millions globally, placing significant strain on healthcare systems, as evidenced by the current opioid crisis. Despite advances in pain management, conventional treatments often fail to address the underlying inflammatory mechanisms that sustain chronic pain. Recent evidence suggests that metaflammation, or meta-inflammation - defined as a chronic, low-grade inflammatory state driven by metabolic dysregulation - plays a pivotal role in the persistence and exacerbation of chronic pain. This review explores the relationship between meta-inflammation and chronic pain, emphasizing the contribution of inflammatory mediators such as tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, and IL-1β. Meta-inflammation is induced by metabolic imbalances, poor dietary habits, gut microbiota alterations, and other lifestyle factors, leading to systemic immune activation. Persistent cytokine signaling results in neuroinflammation, promoting central sensitization and heightened pain perception. Chronic diseases such as obesity, diabetes, cardiovascular disease, and endometriosis share common inflammatory pathways with chronic pain, further supporting the role of meta-inflammation in pain pathophysiology. Given the association between metabolic dysfunction and chronic pain, targeting meta-inflammation presents a novel therapeutic approach to pain management. Dietary modifications, such as the Mediterranean and DASH (Dietary Approaches to…

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