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Interaction of attentional tuning and localisation of pain maxima shift the balance between lateral inhibition and spatial facilitation in nociceptive processing

Nastaj, J.; Szikszay, T. M.; Skalski, J.; Luedtke, K.; Coghill, R. C.; Adamczyk, W. M.

2026-03-18 neuroscience
10.64898/2026.03.14.711815 bioRxiv
Show abstract

Lateral inhibition (LI) is a fundamental neural mechanism across sensory systems and has been proposed to contribute to pain perception. Previous studies suggest that the spatial configuration of noxious stimulation can either amplify or, paradoxically, attenuate perceived pain, consistent with faciliatory or inhibitory interactions within spatially organized neural circuits, respectively. The present study employed a psychophysical framework incorporating attentional-control paradigms to directly probe LI and spatial summation of pain (SSP) in the human nociceptive system. Healthy participants (n = 30) completed a within-subject design including experimental and control trials: LI trials, sham control trial (SHAM), diffuse noxious inhibitory control trials (DNIC) and SSP trials. The spatial configuration of nociceptive input was manipulated by activating different numbers of electrodes, while participants provided either directed pain intensity ratings of a target electrode or overall pain ratings from all activated electrodes. Pain was continuously rated during stimulation periods using an electronic Visual Analogue Scale. Secondary outcomes assessed target pain extraction ability, attentional focus, and the perceived locus of pain maximum. Contrary to theoretical predictions, no evidence for LI emerged. Instead, the results identified facilitatory effects that were strongly modulated by attention and by localization of pain maxima within the complex spatial configuration of nociceptive input. Facilitation was absent when the pain maximum was perceived outside the target electrode and was associated with lower overall pain intensity. Overall pain ratings increased with the number of activated electrodes and were further enhanced during bilateral stimulation, demonstrating robust spatial summation that even extended across the body midline. These findings indicate that facilitatory spatial interactions in pain perception depend on attentional focus and spatial attribution of pain maxima. Significance statementPain depends not only on stimulus intensity, but also on how noxious input is distributed across the body and where attention is directed. This study tested whether spatial interactions in human nociception reduce pain, as predicted by lateral inhibition, or instead enhance it through spatial summation. No evidence for lateral inhibition was found. Instead, pain increased with the number of activated nociceptive sites, including across both sides of the body. These effects were further shaped by attentional focus and by where the pain maximum was perceived. The findings refine current models of pain processing by showing that spatial integration of nociceptive input is predominantly facilitatory and influenced by cognitive and perceptual factors.

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