Exploring the Emerging Link Between Obesity-Induced Meta-Neuroinflammation and Osteoarthritis Pain Mechanisms

Obesity is a complex, heterogeneous, chronic and progressive disease, which correlates with an augmented risk to develop several comorbidities with an enhanced risk of death. In addition to metabolic and cardiovascular diseases, obesity is related to depressive disorders and neurodegenerative diseases, in which gut microbiota dysbiosis plays a central role in triggering the meta-neuroinflammation through the gut-brain axis. In obese patients, the release of inflammatory mediators by dysfunctional adipocytes and the oxidative stress induces meta-neuroinflammation, which have been identified as the main physio-pathological pathway underlying chronic pain syndromes, particularly osteoar-thritis, low back pain, fibromyalgia, headache, and painful diabetic peripheral neu-ropathy. Both the peripheral and the central nervous system are involved in neuroin-flammatory processes, leading to central sensitization and pain chronification. Me-ta-neuroinflammation is also a potential peripheral target of treatment in degenerative joint disease, in order to minimize the traditional pharmacological approaches use. The ultramicronized palmitoylethanolamide is able to control the body weight, to exert neuroprotective, anti-neuroinflammatory and analgesic actions, and to restore intestinal eubiosis, with beneficial effects on mental disorders via the gut-brain axis. Finally, adelmidrol, as a PEA congener, available for intra-articular injection associated with hyaluronic acid, has been shown to modulate meta-neuroinflammation in knee osteo-arthritis.