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These regions may be promising therapeutic targets using non-invasive neuromodulation techniques, including transcranial magnetic stimulation (TMS), transcranial electrical stimulation (TES), and low-intensity focused ultrasound (LIFU). In this review, we synthesize emerging evidence on the function and connectivity of these subregions in both acute and chronic pain, highlighting their differential roles in the sensory, affective, and autonomic contributions to pain processing. We compare the strengths and limitations of the different non-invasive neuromodulatory methods for accessing these deep midline structures and examine how technique-specific and target-specific effects influence analgesic outcomes. We also explore the influence of placebo mechanisms and stimulation context on therapeutic effects. 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