Heterosynaptic long-term depression of craniofacial nociception: divergent effects on pain perception and blink reflex in man

Abstract

Noxious low-frequency stimulation (LFS) of presynaptic nerve fibers induces long-term depression (LTD) of synaptic transmission. In vitro studies suggest a sole homosynaptic effect. Consequently, the present study addressed the hypothesis that LTD of craniofacial nociception in man is mediated by a homosynaptic mechanism. Nociceptive supraorbital afferents were excited by electric pulses via a concentric electrode in ten healthy volunteers. The electrically evoked bilateral blink reflex (BR) was recorded from both orbicularis oculi muscles by surface electrodes. The BR was evoked in blocks of ten electric stimuli each (0.1 Hz) with an interblock interval of 8 min. Conditioning noxious LFS (1 Hz, 20 min) was applied via concentric electrode either to the same site as BR test stimuli (ipsilateral) or to the corresponding contralateral forehead area (contralateral). LFS and test stimulus intensities corresponded to about threefold the pain threshold. After three baseline stimulus blocks, either conditioning ipsilateral or contralateral LFS were applied or stimulation was interrupted for 20 min as a control task. Afterwards, test stimulation blocks were continued for 40 min. Each volunteer participated in all three sessions on different days. Noxious LFS induced LTD of the BR independently from the side of conditioning stimulation. Pain perception decreased after ipsilateral LFS but not after contralateral LFS. The bilateral effect of noxious LFS on the BR provides evidence for heterosynaptic LTD based on bilateral projections of supraorbital nerve afferents onto spinal trigeminal nuclei. The divergent effect on pain perception may be due to a preferential contralateral projection of nociceptive afferents onto reflex interneurons but not onto trigeminothalamic projection neurons.

Evidence of Heterosynaptic LTD in the Human Nociceptive System: Superficial Skin Neuromodulation Using a Matrix Electrode Reduces Deep Pain Sensitivity

“…Similar processes can be assumed for LTD [4]. Prior evidence for heterosynaptic LTD was reported for the human trigeminal system, where noxious LFS applied to skin afferents of the contralateral forehead via a concentric electrode significantly reduced the blink reflex (heterotopic effect), whereas pain sensitivity was decreased only after homotopic LFS [30]. In the present study we extend this finding of heterotopic LTD to deeper tissues after superficial skin stimulation.…”

Long‐term depression of spinal nociception and pain in man: Influence of varying stimulation parameters

“…There is rare information about the most effective stimulation frequency in man, though our findings are in agreement with studies suggesting 1Hz stimulation as appropriate parameter (Ellrich, 2006; Klein et al, 2004; Nilsson et al, 2003). Moreover it was recently published that 1Hz LFS induces sustained depression of trigeminal somatosensory processing in man (Ellrich and Schorr, 2002; Ellrich and Schorr, 2004; Schorr and Ellrich, 2002; Yekta et al, 2006).…”

Electrical low‐frequency stimulation induces long‐term depression of sensory and affective components of pain in healthy man

“…Nociceptive LTD in the trigeminal system (Ellrich, 2006;Schorr, 2002, 2004;Schorr and Ellrich, 2002;Yekta et al, 2006) and the spinal system (Jung et al, 2009;Klein et al, 2004;Nilsson et al, 2003;Rottmann et al, 2008) is reflected in decreased brainstem re-flexes, cortical potentials, and global pain ratings. Nociceptive LTD in the trigeminal system (Ellrich, 2006;Schorr, 2002, 2004;Schorr and Ellrich, 2002;Yekta et al, 2006) and the spinal system (Jung et al, 2009;Klein et al, 2004;Nilsson et al, 2003;Rottmann et al, 2008) is reflected in decreased brainstem re-flexes, cortical potentials, and global pain ratings.…”