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Part of the multifaceted pathophysiology of Complex Regional Pain Syndrome (CRPS) is ascribed to lateralized maladaptive neuroplasticity in sensorimotor cortices, corroborated by behavioral studies indicating that patients present difficulties in mentally representing their painful limb. Such difficulties are widely measured with hand laterality judgment tasks (HLT), which are also used in the rehabilitation of CRPS to activate motor imagery and restore the cortical representation of the painful limb. The potential of these tasks to elicit motor imagery is critical to their use in therapy, yet, the influence of the body's biomechanical constraints (BMC) on HLT reaction time, supposed to index motor imagery activation, is rarely verified. Here we investigated the influence of BMC on the perception of hand postures and movements in upper-limb CRPS. Patients were slower than controls in judging hand laterality, whether or not stimuli corresponded to their painful hand. Reaction time patterns reflecting BMC were mostly absent in CRPS and controls. A second experiment therefore directly investigated the influence of implicit knowledge of BMC on hand movement judgments. Participants judged the perceived path of movement between two depicted hand positions, with only one of two proposed paths that was biomechanically plausible. While the controls mostly chose the biomechanically plausible path, patients did not. These findings show non-lateralized body representation impairments in CRPS, possibly related to difficulties in using correct knowledge of the body's biomechanics. Importantly, they demonstrate the challenge of reliably measuring motor imagery with the HLT, which has important implications for the rehabilitation with these tasks.

Part of the multifaceted pathophysiology of Complex Regional Pain Syndrome (CRPS) is ascribed to lateralized maladaptive neuroplasticity in sensorimotor cortices, corroborated by behavioral studies indicating that patients present difficulties in mentally representing their painful limb. Such difficulties are widely measured with hand laterality judgment tasks (HLT), which are also used in the rehabilitation of CRPS to activate motor imagery and restore the cortical representation of the painful limb. The potential of these tasks to elicit motor imagery is critical to their use in therapy, yet, the influence of the body’s biomechanical constraints (BMC) on HLT reaction time, supposed to index motor imagery activation, is rarely verified. Here we investigated the influence of BMC on the perception of hand postures and movements in upper-limb CRPS. Patients were slower than controls in judging hand laterality, whether or not stimuli corresponded to their painful hand. Reaction time patterns reflecting BMC were mostly absent in CRPS and controls. A second experiment therefore directly investigated the influence of implicit knowledge of BMC on hand movement judgments. Participants judged the perceived path of movement between two depicted hand positions, with only one of two proposed paths that was biomechanically plausible. While the controls mostly chose the biomechanically plausible path, patients did not. These findings show non-lateralized body representation impairments in CRPS, possibly related to difficulties in using correct knowledge of the body’s biomechanics. Importantly, they demonstrate the challenge of reliably measuring motor imagery with the HLT, which has important implications for the rehabilitation with these tasks., SCOPUS: ar.j, info:eu-repo/semantics/published

Pain, besides its contribution to body homeostasis, has also the function of providing information on external stimuli that can potentially harm the body. Such exteroceptive function relies on an optimally integrated multisensory representation of the body and its surrounding space, which is based on the interaction between somatic and extra-somatic stimuli occurring near the body. While the existence of such interactions between nociceptive and visual stimuli has recently been demonstrated, showing that visual stimuli outside the body can impact the perception of nociceptive stimuli and vice versa, their functional role is not clear yet. It is indeed hypothesized that one of the functions of such multisensory representations would be to optimize defensive reactions against threatening stimuli. However, the idea of this potential defensive purpose has, to date, mainly been based on a set of studies conducted in non-human primates. The aim of the present study was to investigate whether interactions between nociceptive and external visual stimuli can shape motor reactions of the stimulated limb. More specifically, we tested in 24 participants whether spinal nociceptive excitability, as measured by the spinal nociceptive withdrawal reflex (NWR) in response to noxious stimuli, can be modulated by external visual stimuli, specifically those approaching the body part on which the nociceptive stimuli are applied. NWRs were elicited by applying transcutaneous electrical stimuli in the sole of the foot of the participants. Depending on the condition, the electrical stimulus was either preceded by a dynamic visual stimulus rapidly approaching a location near the stimulated foot (NWR-visual near condition), a dynamic visual stimulus approaching a location further away from the stimulated foot (NWR-visual far condition), or was applied without any dynamic visual stimulus (NWR only condition). The electrical stimulation could be applied at one out of two possible time points of

Hand laterality judgments (HLT) are widely used to measure body representation difficulties in Complex Regional Pain Syndrome (CRPS), as well as in its rehabilitation, with the aim to activate motor imagery and restore the cortical representation of the affected limb. The potential of these tasks to elicit motor imagery is critical to their use in therapy, yet, the influence of the biomechanical constraints (BMC) on HLT reaction time, supposed to reflect motor imagery, is rarely verified. Here we investigated the influence of BMC on the perception of hand postures and movements. In a first HLT experiment, CRPS patients were significantly slower than controls in judging hand stimuli, whether or not they corresponded to their affected hand. Reaction time patterns reflecting BMC were inconclusive in CRPS and controls, questioning the validity of the task in activating motor imagery. A second experiment therefore directly investigated the influence of implicit knowledge of BMC on perceptual hand movement judgments. Participants judged the perceived path of movement between two depicted hand positions, with only one of two proposed paths that is biomechanically plausible. While the controls mostly chose the biomechanically plausible path, CRPS patients did not, indicating a disturbed perception and/or use of BMC. These findings show non-lateralized body representation impairments in CRPS, possibly related to difficulties in using correct knowledge of the body’s biomechanics. Most importantly, they indicate that it seems highly challenging to measure motor imagery and BMC indexes with the HLT, which has important implications for the rehabilitation with these tasks.

Central sensitization refers to the increased responsiveness of nociceptive neurons in the central nervous system after repeated or sustained peripheral nociceptor activation and is hypothesized to play a key role in the development of chronic pain. A hallmark of central sensitization is an increased sensitivity to noxious mechanical stimuli extending beyond the injured location and referred to as secondary hyperalgesia. Attention could influence the development of central sensitization through its ability to modulate the transmission and processing of nociceptive inputs. Thus, modulating attention could constitute a promising target to prevent central sensitization and the development of chronic pain. It was recently shown that the experimental induction of central sensitization at both forearms of healthy volunteers, using bilateral high-frequency electrocutaneous stimulation (HFS), can be modulated by encouraging participants to selectively focus their attention to one arm, to the detriment of the other arm, resulting in a greater secondary hyperalgesia on the attended arm as compared to the unattended one. Given the potential value of the question being addressed, we conducted a preregistered replication study in a larger independent sample to assess the robustness of the effect, namely the modulatory role of spatial attention on the induction of central sensitization. Using a double-blind within-subject design, we investigated the impact of selective spatial attention on the development of secondary hyperalgesia. Sixty-seven healthy volunteers performed a task that required focusing attention towards one forearm to discriminate innocuous vibrotactile stimuli while HFS was applied on both forearms simultaneously. Our results showed a significant increase in mechanical sensitivity directly and 20 minutes after HFS. However, in contrast to the previous study, we did not find a significant difference in the development of secondary hyperalgesia between the attended

Examining the mechanisms underlying crossmodal interaction between nociceptive and visual stimuli is crucial to understand how humans handle potential bodily threats in their environment. It has recently been shown that nociceptive stimuli can affect the perception of visual stimuli, provided that they occur close together in external space. The present study addresses the question whether these crossmodal interactions between nociceptive and visual stimuli are mediated by the visually perceived proximity between the visual stimuli and the limb on which nociceptive stimuli are applied, by manipulating the presence vs. absence of visual feedback about the position of the stimulated limb. Participants performed temporal order judgments on pairs of visual stimuli, shortly preceded by nociceptive stimuli, either applied on one hand or both hands simultaneously. The hands were placed near the visual stimuli and could either be seen directly, seen through a glass barrier, or hidden from sight with a wooden board. Unilateral nociceptive stimuli induced spatial biases to the advantage of visual stimuli presented near the stimulated hand, which were greater in the conditions in which the hands were seen than in the condition in which vision was prevented. Spatial biases were not modulated by the presence of the glass barrier, minimizing the possibility that the differential effect between the vision and no-vision conditions is solely due to the presence of the barrier between the hands and the visual stimuli. These findings highlight the importance of visual feedback for determining spatial mapping between nociceptive and visual stimuli for crossmodal interaction.

Efficiently reacting to painful events requires an optimally integrated multisensory representation of the body and its surrounding space, coordinating the processing and integration of somatic and extra-somatic stimuli occurring near the body. While such representations would allow optimizing manipulation of innocuous objects, they would also optimize defensive actions against threatening stimuli. Multisensory interactions between nociceptive and near visual stimuli have recently been evidenced. Here we investigated the influence of such nociceptive-visual interaction on the motor excitability of the hand on which nociceptive stimuli are applied in healthy volunteers, by testing whether nociception-induced changes of cortico-spinal excitability (n-CSE) can be differently modulated by visual stimuli presented in the space surrounding the hand vs. visual stimuli presented farther away. CO2-laser nociceptive stimuli were applied on the right hand, followed by 80 ms by a visual stimulus rapidly approaching a location either near or far from the stimulated hand. During each trial, single-pulse transcranial magnetic stimulation over the left M1 hand representation was applied at one out of 3 possible time points (at baseline, 150 or 200 ms after the nociceptive stimulus), eliciting motor-evoked potentials (MEPs) in the right first dorsal interosseous muscle. Conditions comprising only nociceptive or visual stimuli (near or far) were also presented. Preliminary results show a general reduction of MEPs 200 ms after the potential occurrence of the nociceptive stimulus. However, this reduction seemed not differently modulated by near vs. far visual stimuli, suggesting that our experimental setting did not allow to highlight specific visual-nociceptive interaction effects on CSE.

Background and aims. Intense or sustained activation of peripheral nociceptors can inducecentral sensitization. This enhanced responsiveness to nociceptive input of the central nervous system manifests as an increased mechanical pain sensitivity that spreads beyond the site of injury (secondary hyperalgesia), and is thought to be a key mechanism in the development of chronic pain, such as persistent post-operative pain. It is increasingly recognized that emotional and cognitive factors can strongly influence the pain experience. Furthermore, through their potential effects on pain modulation circuits including descending pathways to the spinal cord, it has been hypothesized that they could constitute risk factors for the susceptibility to develop chronic pain. Here, we tested whether, in healthy volunteers, the experimental induction of central sensitization by peripheral nociceptive input can be modulated by selective spatial attention. Methods. While participants performed a somatosensory detection task that required focusing attention towards one of the forearms, secondary hyperalgesia was induced at both forearms using bilateral and simultaneous high-frequency electrical stimulation (HFS) of the skin. Results. HFS induced an increased sensitivity to mechanical pinprick stimuli at both forearms, directly (T1) and 20 minutes (T2) after HFS, confirming the successful induction of secondary hyperalgesia at both forearms. Most importantly, at T2, the HFS-induced increase in pinprick sensitivity as well as the area of secondary hyperalgesia was greater at the attended arm as compared to the non-attended arm. Conclusions. This indicates that top-down attentional factors can modulate the development of central sensitization by peripheral nociceptive input.

Background and aims. Central sensitization (CS) is a use-dependent synaptic plasticity often associated with chronic pain. Studies have shown that the intensity of pain perception and the magnitude of pain-evoked brain responses can be modulated by emotional and cognitive factors. Whether these factors may also affect the induction of CS and resulting hyperalgesia remains largely unknown. Behavioral control over pain has been shown to reduce pain perception. Here, we tested whether pain controllability modulates the experimental induction of CS by high frequency electrical stimulation (HFS) of cutaneous nociceptors, as evaluated by the measurement of secondary hyperalgesia. Methods. HFS was applied to the left or rig ht forearm of healthy participants in two sessions separated by >1 week (five 1-s trains of 100-Hz pulses, 20x detection threshold, inter-train interval: 15-20 s). In the 'control' session, participants self-administered HFS by pushing a button triggering each of the five trains. In the 'no control' session, HFS was delivered at the times corresponding to their delivery in the 'no control' session of another participant. The order of sessions was balanced across participants. The extent of HFS-induced CS and secondary hyperalgesia was assessed by measuring pinprick sensitivity at both forearms, before and 20 minutes after HFS. Results. The increa se in pinprick sensitivity at the HFS-treated forearm was significantly greater in the 'control' vs. the 'no control' sessions. Conclusions. Although previous studies sh owed that self-administration of nociceptive stimuli reduces pain perception, our results indicate behavioral control over nociceptive stimulation paradoxically increases secondary hyperalgesia and probably CS.

Complex Regional Pain Syndrome (CRPS) is characterized by pain, motor and inflammatory symptoms usually affecting one limb. Cognitive difficulties have been reported to affect patients’ ability to represent, perceive and use their affected limb. It is debated whether these difficulties result from deficits in controlling goal-directed movements in space or from a learned strategy to protect the affected limb. In order to dissociate the two hypotheses, patients with upper-limb CRPS were asked to move with their unaffected hand towards visual targets projected at different positions on a horizontal semi-reflexive mirror. By means of a robotic handle placed below the screen, they were asked to move a cursor, to reach and cross lines at their estimated midpoint. In some of the stimulation series, the affected hand was placed below the mirror so that some lines appeared projected onto that hand. Vision of the hands and the robotic handle was preserved or prevented by opening or closing a shutter below the mirror. Lines were displayed on the mirror according to which part of the body was affected (ispi- vs. contralateral) and the actual position of the affected hand (inside vs. outside the workspace). Comparatively to control participants, CRPS patients generally biased their estimation by bisecting the lines towards their left side, irrelative of which part of the body was affected and the position of the affected hand, both in ipsi- and contralateral space, with only a few exceptions. Our results are in line with previous studies having described a visuospatial deficit in CRPS patients and discard the explanation of observed symptoms in terms of learned nonuse strategies, as only the unaffected hand was used to perform the task. It is suggested that CRPS patients can display difficulties to perform tasks requesting visuo-motor coordination, reflecting the complex cortical reorganization occurring in CRPS., SCOPUS: ar.j, info:eu-repo/semantics/published

The present study investigated the influence of nociceptive stimuli on visual stimuli processing according to the relative spatial congruence between the two stimuli of different sensory modalities. Participants performed temporal order judgments on pairs of visual stimuli, one presented near the hand on which nociceptive stimuli were occasionally applied, the other one either to its left or to its right. The visual hemifield in which the stimulated hand and the near visual stimulus appeared was manipulated by changing gaze direction. The stimulated hemibody and the stimulated visual hemifield were therefore either congruent or incongruent, in terms of anatomical locations. Despite the changes in anatomical congruence, judgments were always biased in favor of the visual stimuli presented near the stimulated hand. This indicates that nociceptive-visual interaction may rely on a realignment of the respective initial anatomical representations of the somatic and retinotopic spaces toward an integrated, multimodal representation of external space.

Nociception, the physiological mechanisms specifically processing information about noxious and potentially painful stimuli, has the function to warn the brain about potential body damages (interoception) and about the stimuli that might cause of such damages (exteroception). The exteroceptive function of nociception is thought to rely on multisensory processes integrating the perception of the body with that of the space surrounding it. To support this hypothesis, we exploited the extinction phenomenon usually observed in patients with lesion to one cortical hemisphere. In this vein, we conducted two experiments with healthy subjects to show that the perception of a nociceptive stimulus applied on one hand can also be extinguished in healthy volunteers, as compared to single presentation, by the simultaneous application of a nociceptive stimulus on the contralateral hand, and also by the presentation of a visual stimulus near the contralateral hand. In addition, we observed that visual stimuli presented near the stimulated hand facilitated the perception of nociceptive stimuli applied on that hand. This suggests that the perception of nociceptive events does not only depend on the anatomical and functional integrity of the nociceptive pathways but is also influenced by other sensory experiences about the body and the space around it.

Complex regional pain syndrome (CRPS) is usually characterized by sensory, motor, trophic and autonomic symptoms, but cognitive deficits have also been increasingly recognized as being part of the symptomatology in an important subset of patients over the last few years. These deficits would affect the patients’ ability to mentally represent, perceive and use their affected limb. Importantly, it has recently been shown that deficits in spatial perception are not limited to stimuli applied on the body surface and the perception of the body, but that they can also extend to stimuli presented in external space, i.e., visual ones. More precisely, CRPS patients seemed to pay less attention to visual stimuli presented in the same side of space as the affected limb, and especially those presented close to the limb. However, the exact mechanisms underlying these deficits have yet to be elucidated, such as a possible dissociation between an explanation in terms of visual or proprioceptive input. Indeed, it is not clear whether the observed visuospatial biases depend on the actual sight of the limbs, i.e. the visual perception of the proximity between the visual stimuli and the affected limb. We investigate this question using a visual temporal order judgement (TOJ) task in upper-limb CRPS patients, which is classically used to investigate mechanisms of spatial attention. Patients report which of two visual stimuli presented with various inter-stimulus time intervals has been perceived first. The pairs of visual stimuli, fixed on either a wooden or a transparent board, are presented just above the patients’ hands, one stimulus close to either hand. The visual stimuli and the hands are thus always placed in the same position, but the hands and their proximity to the visual stimuli are either unseen or seen, depending on the use of the wooden or the transparent board, respectively. Preliminary results (N= 12) indicate that, as compared to the condition in which the hands are se

Complex regional pain syndrome (CRPS) is a chronic pain condition associating sensory, motor, trophic and autonomic symptoms in one limb. Probably as a consequence of structural and functional changes at the cortical level, cognitive difficulties have also been reported, affecting the patients’ ability to mentally represent, perceive and use their affected limb. However, the nature of these deficits is still a matter of debate. Recent studies suggest that cognitive deficits are limited to body-related information and body perception, while not extending to external space. We challenged that statement, by using temporal order judgment (TOJ) tasks with tactile (i.e. body) or visual (i.e. extra-body) stimuli in patients with upper-limb CRPS. TOJ tasks allow characterizing cognitive biases to the advantage of one of the two sides of space. While the tactile TOJ tasks did not show any significant results, significant cognitive biases were observed in the visual TOJ tasks, affecting mostly the perception of visual stimuli occurring in the immediate vicinity of the affected limb. Our results clearly demonstrate the presence of visuospatial deficits in CRPS, corroborating the cortical contribution to the CRPS pathophysiology, and supporting the utility of developing rehabilitation techniques modifying visuospatial abilities to treat chronic pain.

The perception of somatosensory stimuli on the body implies the use of different reference frames. It has been shown that they are not only mapped according to a somatotopic reference frame. They are also remapped according to spatial external coordinates in order to provide a common framework to integrate information from different sensory modalities into a multisensory representation of the body space and the space immediately surrounding it. This remapping would be mainly shaped by visual experience. Indeed, it has been demonstrated that crossing the hands over the body midline affects the ability to temporally order two tactile stimuli in sighted but not in early blind participants. This experiment aimed to test this hypothesis using a vibrotactile temporal order judgment (TOJ) task adapted with an adaptive PSI method instead of the method of constant stimuli. This method adapts the stimulus onset asynchrony (SOA) presented in each trial according to the participant’s performance in all the previous trials, allowing to measure precisely the sensitivity of each in a task adapted to the ability of each. Results on the slope showed that all participants performed the task better with the hands uncrossed compared to when their hands were crossed. The blind participants had also a better performance than the sighted controls. These results suggest that both groups cannot be differentiated from each other on the basis of the posture when the task is adapted to the performance of each. Nevertheless, analyses of the SOAs presented to each group showed that the mode of the SOAs presented is significantly lower in the uncrossed compared to the crossed condition in sighted controls, but not in blind individuals. Together, these results indicate that a crossing hand effect could be present in both groups, although more variable in the blind, suggesting that the remapping of tactile stimuli in external coordinates should not be only driven by visual experience.

Despite their high relevance for defending the integrity of the body, crossmodal links between nociception, the neural system specifically coding potentially painful information, and vision are still poorly studied, especially the effects of nociception on visual perception. This study investigated if, and in which time window, a nociceptive stimulus can attract attention to its location on the body, independently of voluntary control, to facilitate the processing of visual stimuli occurring in the same side of space as the limb on which the visual stimulus was applied. In a temporal order judgment task based on an adaptive procedure, participants judged which of two visual stimuli, one presented next to either hand in either side of space, had been perceived first. Each pair of visual stimuli was preceded (by 200, 400, or 600 ms) by a nociceptive stimulus applied either unilaterally on one single hand, or bilaterally, on both hands simultaneously. Results show that, as compared to the bilateral condition, participants’ judgments were biased to the advantage of the visual stimuli that occurred in the same side of space as the hand on which a unilateral, nociceptive stimulus was applied. This effect was present in a time window ranging from 200 to 600 ms, but importantly, biases increased with decreasing time interval. These results suggest that nociceptive stimuli can affect the perceptual processing of spatially congruent visual inputs.

This thesis has been articulated around the question whether nociceptive stimuli and pain can impact the perception of the visual space around the body. This was investigated in healthy volunteers by experimentally applying brief nociceptive stimuli, and in patients suffering from chronic pain in one limb. In healthy participants, we showed that nociceptive stimuli can actually facilitate the processing of visual stimuli. Crucially, such crossmodal facilitation is more efficient when visual stimuli occur in close proximity to the hand on which the nociceptive stimuli are applied. We furthermore showed that patients suffering from upper-limb complex regional pain syndrome paid less attention to visual stimuli occurring in the immediate vicinity of their affected limb. This suggests that the way we perceive and represent our near visual surrounding is influenced by somatic, e.g. nociceptive, sensations and that pain is processed according to a representation of the body that is not limited to its physical boundaries., (PSYE - Sciences psychologiques et de l'éducation) -- UCL, 2017