Disruption of working memory and contralateral delay activity by nociceptive stimuli is modulated by task demands.

ABSTRACT: Top-down processes allow the selection and prioritization of information by limiting attentional capture by distractors, and these mechanisms depend on task demands such as working memory (WM) load. However, bottom-up processes give salient stimuli a stronger neuronal representation and provoke attentional capture. The aim of this study was to examine the effect of salient nociceptive stimuli on WM while manipulating task demands. Twenty-one healthy participants performed a change detection task during which they had to determine whether 2 successive visual arrays were different or the same. Task demands were modulated by manipulating the WM load (set size included 2 or 4 objects to recall) and by the correspondence between the 2 successive visual arrays (change vs no change). Innocuous stimuli (control) or nociceptive stimuli (distractors) were delivered during the delay period between the 2 visual arrays. Contralateral delay activity and laser-evoked potentials were recorded to examine neural markers of visual WM and nociceptive processes. Nociceptive stimuli decreased WM performance depending on task demands (all P < 0.05). Moreover, compared with control stimuli, nociceptive stimuli abolished the increase in contralateral delay activity amplitude for set size 4 vs set size 2 (P = 0.04). Consistent with these results, laser-evoked potential amplitude was not decreased when task demands were high (P = 0.5). These findings indicate that WM may shield cognition from nociceptive stimuli, but nociceptive stimuli disrupt WM and alter task performance when cognitive resources become insufficient to process all task-relevant information.

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

Bilateral noxious inputs interact in the brain to provide a better representation of physical threat. In the present study, we investigated the effects of spatial attention and limb position on this interaction. Painful laser stimuli were applied randomly on the right hand or on both hands, while varying spatial attention (focal or overall) and limb position (hands near or far from each other). Pain perception and laser-evoked potentials (N1, N2, P2) were compared between conditions in 27 healthy volunteers. Compared with unilateral stimulation, bilateral stimulation increased pain (p = .004), the N2 (p = .0015) and P2 (p < .001) amplitude. The effects on pain and the P2 were greater when hands were in the near compared with the far position (p < .05). The effect on pain was also greater for overall compared with focal pain rating (p = .003). In addition, the N1 amplitude was greater for bilateral stimulation when hands were in the far compared with the near position (p = .01). These results show that increased brain responses and pain for bilateral compared with unilateral noxious stimulation are modulated differentially by spatial attention and limb position. This suggests that the integration of noxious inputs occurs through partially independent pain-related processes, that it is modulated by limb position, and that it is partially independent of pain perception. We propose that this is necessary to produce coordinated, flexible and adapted defensive responses.

Spinal and Cerebral Integration of Noxious Inputs in Left-handed Individuals.

Some pain-related information is processed preferentially in the right cerebral hemisphere. Considering that functional lateralization can be affected by handedness, spinal and cerebral pain-related responses may be different between right- and left-handed individuals. Therefore, this study aimed to investigate the cortical and spinal mechanisms of nociceptive integration when nociceptive stimuli are applied to right -handed vs. left -handed individuals. The NFR, evoked potentials (ERP: P45, N100, P260), and event-related spectral perturbations (ERSP: theta, alpha, beta and gamma band oscillations) were compared between ten right-handed and ten left-handed participants. Pain was induced by transcutaneous electrical stimulation of the lower limbs and left upper limb. Stimulation intensity was adjusted individually in five counterbalanced conditions of 21 stimuli each: three unilateral (right lower limb, left lower limb, and left upper limb stimulation) and two bilateral conditions (right and left lower limbs, and the right lower limb and left upper limb stimulation). The amplitude of the NFR, ERP, ERSP, and pain ratings were compared between groups and conditions using a mixed ANOVA. A significant increase of responses was observed in bilateral compared with unilateral conditions for pain intensity, NFR amplitude, N100, theta oscillations, and gamma oscillations. However, these effects were not significantly different between right- and left-handed individuals. These results suggest that spinal and cerebral integration of bilateral nociceptive inputs is similar between right- and left-handed individuals. They also imply that pain-related responses measured in this study may be examined independently of handedness.

Cortical interaction of bilateral inputs is similar for noxious and innocuous stimuli but leads to different perceptual effects.

The cerebral integration of somatosensory inputs from multiple sources is essential to produce adapted behaviors. Previous studies suggest that bilateral somatosensory inputs interact differently depending on stimulus characteristics, including their noxious nature. The aim of this study was to clarify how bilateral inputs evoked by noxious laser stimuli, noxious shocks, and innocuous shocks interact in terms of perception and brain responses. The experiment comprised two conditions (right-hand stimulation and concurrent stimulation of both hands) in which painful laser stimuli, painful shocks and non-painful shocks were delivered. Perception, somatosensory-evoked potentials (P45, N100, P260), laser-evoked potentials (N1, N2 and P2) and event-related spectral perturbations (delta to gamma oscillation power) were compared between conditions and stimulus modalities. The amplitude of negative vertex potentials (N2 or N100) and the power of delta/theta oscillations were increased in the bilateral compared with unilateral condition, regardless of the stimulus type (P < 0.01). However, gamma oscillation power increased for painful and non-painful shocks (P < 0.01), but not for painful laser stimuli (P = 0.08). Despite the similarities in terms of brain activity, bilateral inputs interacted differently for painful stimuli, for which perception remained unchanged, and non-painful stimuli, for which perception increased. This may reflect a ceiling effect for the attentional capture by noxious stimuli and warrants further investigations to examine the regulation of such interactions by bottom-up and top-down processes.

Effects of chiropractic spinal manipulation on laser-evoked pain and brain activity.

The aim of this study was to examine the mechanisms underlying hypoalgesia induced by spinal manipulation (SM). Eighty-two healthy volunteers were assigned to one of the four intervention groups: no intervention, SM at T4 (homosegmental to pain), SM at T8 (heterosegmental to pain) or light mechanical stimulus at T4 (placebo). Eighty laser stimuli were applied on back skin at T4 to evoke pain and brain activity related to Aδ- and C-fibers activation. The intervention was performed after 40 stimuli. Laser pain was decreased by SM at T4 (p = 0.028) but not T8 (p = 0.13), compared with placebo. However, brain activity related to Aδ-fibers activation was not significantly modulated (all p > 0.05), while C-fiber activity could not be measured reliably. This indicates that SM produces segmental hypoalgesia through inhibition of nociceptive processes that are independent of Aδ fibers. It remains to be clarified whether the effect is mediated by the inhibition of C-fiber activity.

Segmental Chiropractic Spinal Manipulation Does not Reduce Pain Amplification and the Associated Pain-Related Brain Activity in a Capsaicin-Heat Pain Model.

Musculoskeletal injuries lead to sensitization of nociceptors and primary hyperalgesia (hypersensitivity to painful stimuli). This occurs with back injuries, which are associated with acute pain and increased pain sensitivity at the site of injury. In some cases, back pain persists and leads to central sensitization and chronic pain. Thus, reducing primary hyperalgesia to prevent central sensitization may limit the transition from acute to chronic back pain. It has been shown that spinal manipulation (SM) reduces experimental and clinical pain, but the effect of SM on primary hyperalgesia and hypersensitivity to painful stimuli remains unclear. The goal of the present study was to investigate the effect of SM on pain hypersensitivity using a capsaicin-heat pain model. Laser stimulation was used to evoke heat pain and the associated brain activity, which were measured to assess their modulation by SM. Eighty healthy participants were recruited and randomly assigned to one of the four experimental groups: inert cream and no intervention; capsaicin cream and no intervention; capsaicin cream and SM at T7; capsaicin cream and placebo. Inert or capsaicin cream (1%) was applied to the T9 area. SM or placebo were performed 25 min after cream application. A series of laser stimuli were delivered on the area of cream application (1) before cream application, (2) after cream application but before SM or placebo, and (3) after SM or placebo. Capsaicin cream induced a significant increase in laser pain (p < 0.001) and laser-evoked potential amplitude (p < 0.001). However, SM did not decrease the amplification of laser pain or laser-evoked potentials by capsaicin. These results indicate that segmental SM does not reduce pain hypersensitivity and the associated pain-related brain activity in a capsaicin-heat pain model.

Chiropractic Spinal Manipulation Prevents Secondary Hyperalgesia Induced by Topical Capsaicin in Healthy Individuals.

Background and Aims: Spinal manipulation (SM) is currently recommended for the management of back pain. Experimental studies indicate that the hypoalgesic mechanisms of SM may rely on inhibition of segmental processes related to temporal summation of pain and, possibly, on central sensitization, although this remains unclear. The aim of this study was to determine whether experimental back pain, secondary hyperalgesia, and pain-related brain activity induced by capsaicin are decreased by segmental SM. Methods: Seventy-three healthy volunteers were randomly allocated to one of four experimental groups: SM at T5 vertebral level (segmental), SM at T9 vertebral level (heterosegmental), placebo intervention at T5 vertebral level, or no intervention. Topical capsaicin was applied to the area of T5 vertebra for 40 min. After 20 min, the interventions were administered. Pressure pain thresholds (PPTs) were assessed outside the area of capsaicin application at 0 and 40 min to examine secondary hyperalgesia. Capsaicin pain intensity and unpleasantness were reported every 4 min. Frontal high-gamma oscillations were also measured with electroencephalography. Results: Pain ratings and brain activity were not significantly different between groups over time (p > 0.5). However, PPTs were significantly decreased in the placebo and control groups (p < 0.01), indicative of secondary hyperalgesia, while no hyperalgesia was observed for groups receiving SM (p = 1.0). This effect was independent of expectations and greater than placebo for segmental (p < 0.01) but not heterosegmental SM (p = 1.0). Conclusions: These results indicate that segmental SM can prevent secondary hyperalgesia, independently of expectations. This has implications for the management of back pain, particularly when central sensitization is involved.

Integration of bilateral nociceptive inputs tunes spinal and cerebral responses.

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.

Cortical integration of bilateral nociceptive signals: when more is less.

Integration of nociceptive information is essential to produce adapted responses, to promote body integrity and survival. However, how the brain integrates nociceptive inputs from different body areas remains unknown. The aim of this study was to examine the cortical integration of bilateral nociceptive inputs evoked by laser heat stimuli. Sixteen healthy volunteers (8 F, 8 M; age: 25.5 ± 4.3) were recruited to participate in one session during which painful laser stimuli were applied to their hands with 2 Nd:YAP laser systems. Electroencephalographic activity was recorded to measure laser-evoked potentials and event-related spectral perturbations. Twenty nociceptive stimuli were applied in each of the 4 counterbalanced conditions: (1) right hand, (2) left hand, and both hands with (3) attention to the right or (4) attention to the left. Compared with unilateral conditions, N2 and P2 peak amplitude as well as gamma oscillation power were decreased in bilateral conditions (P < 0.05), but these effects were not affected by the direction of attention (P > 0.1). By contrast, pain was not significantly different in any condition (P > 0.05). These findings show that although more nociceptive inputs reach the brain with multiple nociceptive stimuli, their sensory representation is decreased while pain perception remains unchanged. These interactions between cerebral processing of nociceptive information from different body regions could support coordinated behavioral responses when pain origins from multiple sources.

Quantification of joint alignment and stability during a single leg stance task in a knee osteoarthritis cohort.

BACKGROUND: Knee osteoarthritis alters joint stability but its kinematics during functional weight-bearing tasks remain unclear. We propose and validate an assessment technique for the quantification of knee alignment and stability in patients during a short single leg stance task. METHODS: Three-dimensional knee kinematics were acquired non-invasively from 31 knee osteoarthritis patients (subdivided as moderate or severe) and 15 asymptomatic individuals during six short single-leg stance tasks. Data of participants achieving ≥3 trials were retained. From flexion-extension signals, a data treatment method compared the average between-trial root-mean-square error (RMSE) across trial triplets, and the average within-trial range of movement (RoM) for two data windows. From secondary knee motions (ab/adduction and int/external rotations, anteroposterior and mediolateral translations), we extracted measures characterizing alignments (mean), largest deviations (maximum, minimum), and extent of micro-adjustments (RoM, length of knee excursion). Their sensitivity to disease and severity was determined using an ANOVA, and between-trial repeatability using ICC2,3. RESULTS: Ninety-four percent of patients achieved ≥3 trials. The retained trial triplet and window reduced the RMSE (2.15 to 1.54) and RoM (4.9° to 1.77°) for flexion-extension. Mean, minimum, and maximum measures were sensitive to disease for anteroposterior translations, and to severity for ab/adduction (P < 0.05). High repeatability was found for those measures (ICC ≥0.84). RoM and length of knee excursion, although sensitive to disease for anteroposterior translations, had lower ICC. CONCLUSION: The proposed technique is feasible and exposed measures of knee alignment sensitive to knee osteoarthritis, for instance, an anterior femoral shift and an increased adduction malalignment with greater severity.