McPhee ME, Graven-Nielsen T., et al. - Given the high disability linked with chronic low back pain (CLBP) but often without an identifiable source, researchers conducted a randomized-controlled cross-over pilot trial using active vs sham medial prefrontal cortex (mPFC) high-definition transcranial direct current stimulation (HD-tDCS) for 3 consecutive days to improve descending pain inhibitory function. Twelve CLBP patients with an average visual analogue scale (VAS) pain intensity of 3.0±1.5 and pain duration of 5.3±2.6 years were included in the study. Active and sham HD-tDCS did not significantly differ in psychophysical (pressure pain threshold, conditioned pain modulation (CPM), and temporal summation of pain), symptomatology, or psychological outcomes on Day4 and Day21. A negative correlation was observed between CPM-effects at Day1 and change in CPM-effect at Day4 after active HD-tDCS. Several factors accounted for lack of effectiveness, including that patients did not exhibit impaired CPM at baseline. Pain, psychological nor psychophysical outcomes were not changed via medial prefrontal HD-tDCS. Response may vary based on on baseline pain inhibitory effectiveness, as suggested by correlational analysis, with patients who had severe impairments in descending pain inhibitory mechanisms experiencing the best effects.