Optimization of Pulsed Electromagnetic Field Parameters Attenuates Mechanical Hyperalgesia and Selectively Modulates Inflammatory and Oxidative Markers in a CFA‐Induced Inflammatory Pain Mouse Model

Pain poses a global challenge involving sensory, cognitive, and emotional mechanisms, necessitating effective treatments. In this study, we evaluate the effects of pulsed electromagnetic field (PEMF), a noninvasive low‐frequency signal with potential anti‐inflammatory effects, in male Swiss mice after a complete Freund's adjuvant (CFA)‐induced inflammation. The aim was to identify the optimal PEMF pulse frequency (5, 50, or 75 Hz) and treatment duration (10, 20, or 30 min) for analgesic effects, assessed by mechanical hyperalgesia, and to investigate peripheral (paw) and central (spinal cord, hippocampus, and prefrontal cortex) inflammatory and oxidative responses following CFA administration. Emotion‐related behaviors were also assessed; however, CFA did not induce detectable anxiety‐ or depression‐like alterations under the experimental conditions used. The best antihyperalgesic effect was at 75 Hz, particularly with 20 and 30 min of treatment, without affecting paw edema. A 20‐min PEMF treatment at 75 Hz reduced TNF levels in the paw and increased SOD enzyme activity in the paw and spinal cord, indicating anti‐inflammatory and antioxidant effects both peripherally and centrally. These results confirm PEMF's antihyperalgesic effect, identifying 75 Hz and 20 min as optimal parameters. Understanding PEMF mechanisms could lead to new therapeutic targets, improving pain management in patients with inflammatory conditions, and altering the underlying pathological process.