Peroxisome proliferator-activated receptor gamma: A promising therapeutic target for the treatment of chronic pain.

Chronic pain represents an incapacitating medical condition that profoundly impacts the patients' quality of life. Managing chronic pain poses a significant challenge for healthcare professionals due to its multifaceted nature and the limited effectiveness of current treatment options. Therefore, novel therapeutic interventions are crucially required for the management of chronic pain. Peroxisome proliferator-activated receptor gamma (PPARγ), a nuclear receptor, exerts regulatory effects on physiological processes such as glucose and lipid metabolism. Emerging studies demonstrate that PPARγ is a critical regulator of the expression of various genes, including those of anti-inflammatory cytokines and antioxidant enzymes. Substantial evidence indicates decreased expression of PPARγ in the sciatic nerve, dorsal root ganglia, and spinal cord dorsal horn in animal models of chronic pain. Furthermore, natural or synthetic PPARγ agonists had inhibitory effects on nociceptive hypersensitivity in various animal models of chronic pain. This review summarizes and discusses preclinical evidence demonstrating the therapeutic potential of PPARγ agonists in chronic pain management. The available evidence indicates that PPARγ activation reduces chronic pain by inhibiting neuroinflammation and oxidative stress as well as modulation of opioidergic system. Overall, the use of PPARγ agonists is a promising therapeutic approach for treating chronic pain; however, further research regarding its detailed mechanisms is warranted.