Electrical low-frequency stimulation (LFS) of cutaneous afferents reliably induces long-term depression (LTD) of nociception and pain in man. In this study LFS effects on cerebral activation were investigated by functional magnetic resonance imaging (fMRI). In 17 healthy volunteers, nociceptive fibers of right hand dorsum were electrically stimulated via a concentric electrode. Test stimulation sessions consisted of three alternating stimulation periods and rest periods. They were performed before (Pre) and after (Post) conditioning LFS (1200 stimuli, 1Hz) or 20 min break (Control). Volunteers rated sensory and affective pain perception. Before LFS, test stimulation produced activation in bilateral primary and secondary somatosensory cortex (S1,S2), insula, anterior cingulate cortex (ACC), superior temporal cortex (STG), prefrontal cortex and right inferior parietal lobule (IPL). After LFS, exclusively right IPL was activated. Contrast between Pre and Post LFS indicated significant activity decrease in bilateral S1,S2, and ACC and right insula, IPL, and STG. Pre Control and Pre LFS were not different. Activity in Control experiments remained unchanged. Sensory and affective pain rating solely decreased after LFS. Subsequent regression analysis showed significant correlation between pain relief and increased activity after LFS in ACC, anterior insula, striatum, frontal and temporal cortex. The study revealed LTD of pain-related cerebral activation, involving sensory, affective, cognitive, and attentional processes. Positive correlation between pain relief and increased brain activation after LFS may indicate involvement of endogenous pain control mechanisms in LTD. These experiments may help to judge the potency of LTD for future chronic pain treatment.
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