Heterotopic low-frequency stimulation induces nociceptive LTD within the same central receptive field in man

Electrical low-frequency stimulation (LFS) evokes long-term depression (LTD) of nociception. Human studies suggested a strictly homotopic organization. This study hypothesizes that even heterotopic LFS evokes LTD within the same receptive field (RF). In 33 healthy volunteers, painful electrical test stimulation and LFS were applied to the low back by a concentric electrode (ExpBack) and to the forearm by a multiarray electrode (ExpArm). Volunteers rated pain perception during test stimulation that was applied before and after LFS. In ExpBack, test stimuli were administered within the right T12 dermatome. LFS was applied heterotopically within the same RF or remote in dermatome T8. In ExpArm, test stimulation was carried out in the center of the RF whereas LFS was applied to the center, margin, or outside the RF. In ExpBack (n = 20), pain ratings decreased significantly stronger in T12 than in T8 dermatome (P < 0.01). In ExpArm (n = 20), LFS to the center of the RF induced a stronger pain reduction than LFS applied outside the RF (P < 0.001). This study demonstrates a heterosynaptic organization of LTD within the same RF. Profound knowledge about RF involvement on LTD seems crucial in order to judge the quality of LFS as a possible neuromodulatory treatment of pain.