Repetitive Transcranial Magnetic Stimulation of the mPFC Ameliorates Stress‐Induced Hyperalgesia by Alleviating Microglia Activation in Rats

PURPOSE: Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive neuromodulation technique that uses magnetic fields to stimulate or inhibit specific populations of neurons in the brain. rTMS targeting the cortex has emerged as an effective treatment for chronic pain. It is established that stress can heighten pain sensitivity, a condition termed stress-induced hyperalgesia (SIH). However, neither direct evidence for rTMS treatment of SIH nor a clear understanding of its therapeutic mechanisms has been established. METHODS: In this article, we studied the effectiveness of rTMS in SIH using a rat CFA (complete Freund's adjuvant) + SPS (single-prolonged stress)-induced model. Following SPS + CFA treatment, a significant enhancement in both medial prefrontal cortex (mPFC) microglia activation by immunohistochemistry and Western blot analyses and mechanical allodynia was observed, as compared with the application of SPS or CFA alone. Compared to the untreated SPS + CFA model group, 10 Hz rTMS treatment significantly elevated the paw withdrawal threshold. This effect was also significantly greater than that observed in the group receiving 1 Hz rTMS. Moreover, the application of 10 Hz rTMS inhibited microglial activation in the SPS + CFA model, along with alleviating associated anxiety-like behaviors. FINDS AND CONCLUSION: These results suggest that rTMS might have an effect on the treatment of SIH.