POTENTIAL USE OF GLP-1 RECEPTOR AGONISTS IN THE MANAGEMENT OF CHRONIC PAIN SYNDROMES: ANTI-INFLAMMATORY AND NEUROPROTECTIVE PERSPECTIVES

Abstract

Chronic pain syndromes remain a major clinical and public health challenge because of their multifactorial pathophysiology, frequent refractoriness to standard treatment, and marked effects on quality of life, disability, sleep, psychological well-being, and work capacity. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), initially developed for type 2 diabetes and obesity, have recently attracted growing interest beyond metabolic medicine because their biological actions appear to extend to anti-inflammatory, antioxidative, neuroprotective, and cytoprotective pathways. These pleiotropic properties are potentially relevant to chronic pain, which is increasingly understood as a condition sustained not only by nociceptive input but also by neuroinflammation, glial activation, oxidative stress, maladaptive neuronal plasticity, mitochondrial dysfunction, and metabolic dysregulation. This narrative review examines the current biological and translational rationale for GLP-1RAs in chronic pain syndromes, with emphasis on neuropathic pain, diabetic peripheral neuropathy, migraine-related central sensitization, fibromyalgia-related mechanisms, osteoarthritis-associated pain, inflammatory musculoskeletal pain, and visceral pain. Available evidence suggests that GLP-1 receptor activation may modulate several processes implicated in pain chronification, including pro-inflammatory cytokine signaling, microglial activation, oxidative stress, mitochondrial dysfunction, and impaired neuronal resilience. Experimental studies also indicate possible involvement of IL-10-mediated anti-inflammatory signaling, AMPK/NF-kappaB pathway modulation, and broader neuroimmune regulation. However, the current evidence base remains heterogeneous and is still dominated by preclinical studies, mechanistic reviews, and early observational data. Human evidence in non-diabetic chronic pain populations remains limited, and in many settings it is difficult to separate direct analgesic effects from indirect benefits related to weight loss, improved glycemic control, reduced systemic inflammation, or improved function. At present, GLP-1RAs should therefore be regarded as biologically plausible and clinically promising, but still investigational, candidates in chronic pain management rather than established analgesic therapies. Further translational work and adequately powered prospective clinical studies are required to clarify efficacy, safety, mechanism-specific effects, and phenotype-specific patient selection.