Integration of bilateral nociceptive inputs tunes spinal and cerebral responses

Abstract

Together with the nociceptive system, pain protects the body from tissue damage. For instance, when the RIII-reflex is evoked by sural nerve stimulation, nociceptive inputs activate flexor muscles and inhibit extensor muscles of the affected lower limb while producing the opposite effects on the contralateral muscles. But how do the spinal cord and brain integrate concurrent sensorimotor information originating from both limbs? This is critical for evoking coordinated responses to nociceptive stimuli, but has been overlooked. Here we show that the spinal cord integrates spinal inhibitory and descending facilitatory inputs during concurrent bilateral foot stimulation, resulting in facilitation of the RIII-reflex and bilateral flexion. In these conditions, high-gamma oscillation power was also increased in the dorsolateral prefrontal, anterior cingulate and sensorimotor cortex, in accordance with the involvement of these regions in cognitive, motor and pain regulation. We propose that the brain and spinal cord can fine-tune nociceptive and pain responses when nociceptive inputs arise from both lower limbs concurrently, in order to allow adaptable behavioural responses.

Effects of spatial attention and limb position on the cortical interaction of bilateral noxious inputs

“…The results show that bilateral stimulation leads to a greater increase in pain perception when the hands are in the near compared with the far position, consistent with the effect on the P2 and previous studies (Lautenbacher et al, 2007;Quevedo & Coghill, 2007). The results may also explain why bilateral noxious stimuli increased pain when applied on both feet (close from each other), but not on both hands (70 cm apart) or on a foot and a hand (Northon et al, 2019(Northon et al, , 2021a(Northon et al, , 2021bRustamov et al, 2019). Although this should be examined in future studies, it could be speculated that this effect is related to perceptual fusion and to the overlap in the limb-centered peripersonal space of each limb .…”

“…In previous studies, it was shown that spatial attention can modulate pain-related brain responses, especially when the features of the concurrent stimulus are distinct from the attended stimulus (Van Ryckeghem et al, 2013;Torta et al, 2017). In contrast, it was shown that attending and rating the right or left noxious stimulus during bilateral stimulation does not modulate pain-related brain responses (Blöchl et al, 2015;Northon et al, 2019;Rustamov et al, 2019). In the present study, instructions for pain ratings were adapted from previous studies on the spatial integration of pain (Lautenbacher et al, 2007;Nielsen & Arendt-Nielsen, 1997b;Quevedo & Coghill, 2007.…”

“…Consistent with these findings, several participants of the present study (30%) showed decreased N2 and P2 amplitude or no change, for bilateral compared with unilateral stimulation, although the group effect showed significantly increased N2 and P2 amplitude. Notwithstanding, the most common effect of bilateral compared with unilateral noxious stimulation (electrical or laser) on event-related potentials is an increase of the N2 and P2 (laser) as well as the N100 (electrical), but not the P260 (electrical) (Northon et al, 2019(Northon et al, , 2021a(Northon et al, , 2021bRustamov et al, 2019). Considering the view that event-related potentials are not specific to pain but mostly reflect a multimodal salience detection system (Iannetti et al, 2008), the results suggest that the integration of bilateral noxious inputs may serve to generate a F I G U R E 4 Lateralized event-related potentials.…”

“…To provide a better estimate of potential bodily threat as well as defensive behaviors that are adapted to the context and the environment, the cerebral cortex integrates sensory inputs from different sources and modalities (Tabor et al, 2017). It has been shown that bilateral noxious inputs interact in the brain, leading to increased or decreased vertex evoked potential amplitude (Northon et al, 2019(Northon et al, , 2021a(Northon et al, , 2021bRustamov et al, 2019). However, the factors that determine or influence this modulation remain unclear.…”

“…This may modulate the integration of bilateral noxious inputs in the brain to generate a better representation of the physical threat, as the distance between hands affects the likelihood that both stimuli originate from a common source. This may partly explain why bilateral noxious stimuli applied on the feet (near from each other), but not on the hands (inter-limb distance of 70 cm) increase pain and pain-related brain activity compared with unilateral stimulation (Northon et al, 2019(Northon et al, , 2021a(Northon et al, , 2021bRustamov et al, 2019).…”