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Although the inhibitory action that tactile stimuli can have on pain is well documented, the precise timing of the interaction between the painful and non-painful stimuli in the central nervous system is unclear. The aim of this study was to investigate this issue by measuring the timing of the amplitude modulation of laser evoked potentials (LEPs) due to conditioning non-painful stimuli. LEPs were recorded from 31 scalp electrodes in 10 healthy subjects after painful stimulation of the right arm (C6-C7 dermatomes). Non-painful electrical stimuli were applied by ring electrodes on the second and third finger of the right hand. Electrical stimuli were delivered at +50, +150, +200 and +250 ms interstimulus intervals (ISIs) after the laser pulses. LEPs obtained without any conditioning stimulation were used as a baseline. As compared to the baseline, non-painful electrical stimulation reduced the amplitude of the vertex N2/P2 LEP component and the laser pain rating when electrical stimuli followed the laser pulses only at +150 and +200 ms ISIs. As at these ISIs the collision between the non-painful and painful input is likely to take place at the cortical level, we can conclude that the late processing of painful (thermal) stimuli is partially inhibited by the processing of non-painful (cutaneous) stimuli within the cerebral cortex. Moreover, our results do not provide evidence that non-painful inputs can inhibit pain at a lower level, including the spinal cord., (© 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Cardiac syndrome X (CSX) is characterized by effort angina, ST-segment depression during stress tests and normal coronary arteries. Abnormal nociception was suggested in these patients by studies showing a reduced cardiac pain threshold; furthermore, we recently found a lack of habituation to pain stimuli using recording of laser evoked potentials (LEPs). In CSX patients with severe angina, spinal cord stimulation (SCS) was shown to improve symptoms. In this study we investigated whether, in these patients, SCS has any effects on the excitability of the nociceptive system, assessed by LEPs recording. We studied 16 CSX patients (61.6+/-7 years; 4 men) who underwent SCS for refractory angina. Cortical LEPs were recorded during stimulation of the chest and right-hand during active SCS (SCS-ON) and in the absence of SCS (SCS-OFF), using a randomized cross-over design. Three sequences of painful stimuli were applied at each site during each test. During the first sequence of chest stimuli, the N2/P2 LEP amplitude was higher during the SCS-ON, compared to the SCS-OFF phase (18.2+/-7.8 vs. 11.5+/-4.4 microV, P=0.006). The N2/P2 amplitude did not change significantly across the three stimulation sequences during the SCS-OFF phase (P=0.22), whereas it decreased progressively during the second and third sequence (to 87.1+/-29.5% and 76.4+/-24.1%, respectively) compared with the first sequence, during the SCS-ON phase (P=0.014). Similar results were observed during right-hand stimulation. Our study shows that in CSX patients SCS is able to restore habituation to peripheral pain stimuli. This effect might contribute to restore the ability of CSX patients to better tolerate cardiac pain.

Seeing actions, emotions and feelings of other individuals may activate resonant mechanisms that allow the empathic understanding of others' states. Being crucial for implementing pro-social behaviors, empathy is considered as inherently altruistic. Here we explored whether the personal experience of pain make individuals less inclined to share others' pain. We used laser-evoked potentials (LEPs) to explore whether observation of painful or non-noxious stimuli delivered to a stranger model induced any modulation in the pain system of onlookers who were suffering from pain induced by the laser stimuli. After LEPs recording, participants rated intensity and unpleasantness of the laser pain, and of the pain induced by the movie in themselves and in the model. Mere observation of needles penetrating the model's hand brought about a specific reduction of the N1/P1 LEP component, related to the activation of somatic nodes of the pain matrix. Such reduction is stronger in onlookers who rated the pain intensity induced by the pain movie as higher in themselves and lower in the model. Conversely, the N2a-P2 component, supposedly associated to affective pain qualities, did not show any specific modulation during observation of others' pain. Thus, viewing 'flesh and bone' pain in others specifically modulates neural activity in the pain matrix sensory node. Moreover, this socially-derived inhibitory effect is correlated with the intensity of the pain attributed to self rather than to others suggesting that being in pain may bias the empathic relation with stranger models towards self-centred instead than other-related stances.

Background & Aims: In various chronic pain conditions cortical reorganization seems to play a role in the manifestations. The aim of this study was to investigate cortical reorganization in patients with pain caused by chronic pancreatitis., Methods: Twelve healthy subjects and 10 patients with chronic pancreatitis were included. The esophagus, stomach, and duodenum were stimulated electrically at the pain threshold using a nasal endoscope. The electroencephalogram was recorded from 64 surface electrodes and event-related brain potentials (EPs) were obtained., Results: As compared with healthy subjects, the patient group showed decreased latencies of the early EP components (N1, P < .001; P1, P = .02), which is thought to reflect the exogenous brain pain processing specifically. Source analysis showed that the dipolar activities corresponding to the early EPs were located consistently in the bilateral insula, in the anterior cingulate gyrus, and in the bilateral secondary somatosensory area. The bilateral insular dipoles were localized more medial in the patient group than in the healthy subjects after stimulation of all 3 gut segments (P < .01). There also were changes in the cingulate cortex where the neuronal source was more posterior in patients than in controls to stimulation of the esophagus (P < .05)., Conclusions: The findings indicate that pain in chronic pancreatitis leads to changes in cortical projections of the nociceptive system. Such findings also have been described in somatic pain disorders, among them neuropathic pain. Taken together with the clinical data this suggests a neuropathic component in pancreatic pain, which may influence the approach to treatment.

Previous electroencephalographic (EEG) evidence has shown event-related desynchronization (ERD) of alpha rhythms before predictable painful stimuli, as a possible neural concomitant of attentional preparatory processes (Babiloni, C., Brancucci, A., Babiloni, F., Capotosto, P., Carducci, F., Cincotti, F., Arendt-Nielsen, L., Chen, A.C., Rossini, P.M., 2003. Anticipatory cortical responses during the expectancy of a predictable painful stimulation. A high-resolution electroencephalography study. Eur. J. Neurosci. 18 (6) 1692-700). This study tested the hypothesis that alpha ERD before predictable painful stimuli is reduced as an effect of distraction. A visual warning stimulus preceded a laser painful stimulation, which was strictly followed by visual imperative stimuli. In the Pain (control) condition, no task was required after the imperative stimuli. In the Pain + Movement condition, subjects had to perform a movement of the right index finger. In the Pain + Cognition condition, they had to mentally perform an arithmetical task. EEG data were recorded in 10 subjects from 30 electrodes. Artifact-free recordings were spatially enhanced by surface Laplacian transformation. Alpha ERD was computed at three alpha sub-bands according to subjects' individual alpha frequency peak (i.e., about 6-8 Hz, 8-10 Hz, 10-12 Hz). Compared to the control condition, the subjects reported a significantly lower stimulus intensity perception and unpleasantness in the Pain + Movement and Pain + Cognition conditions. In addition, there was a cancellation of the alpha 3 ERD (i.e., about 10-12 Hz) in Pain + Cognition condition and even a generation of a statistically significant alpha 3 ERS in Pain + Movement condition. These effects were maximum over fronto-central midline. These results suggest that distraction during the expectancy of pain is related to a reduced neural desynchronization of fronto-central midline alpha rhythms (i.e., reduced cortical activation) towards an overt hyper-synchronization (cortical idling).

Aims: Previous studies suggested that an enhanced pain sensitivity is present in patients with cardiac syndrome X (SX). We investigated whether SX patients present abnormalities in the electrical cerebral signals generated by pain stimuli., Methods and Results: Cortical laser evoked potentials (LEPs) were recorded in 16 SX patients, in 10 patients with refractory angina due to obstructive coronary artery disease (CAD) and in 13 healthy controls. LEPs were recorded during stimulation of chest and right hand dorsum. Three sequences of painful stimuli were applied at each site. Subjective pain rating was assessed by a 0-100 mm visual analogic scale (VAS). Basal LEPs did not differ among groups and there were no differences for most LEP components across the repetitions of stimuli. However, the amplitude of the N2/P2 LEP component, specifically reflecting cortical pain processing, decreased across the three sequences of stimuli in controls and CAD patients, but not in SX patients. Compared with the first sequence, the N2/P2 amplitude during the third sequence of stimuli in the three groups was 77+/-16, 56+/-24, and 99+/-34%, respectively, for chest (P=0.001), and 63+/-31, 72+/-17, and 98+/-46%, respectively, for right hand (P=0.03) stimulation. The changes in VAS pain score across the three sequences paralleled those of N2/P2 amplitude., Conclusion: Our data show that in SX patients, central handling of painful stimuli is characterized by inadequate habituation, which might play a role in determining the peculiar clinical characteristics of anginal chest pain of these patients.

The aim of this study was to model the cerebral generators following painful electrical stimulation of the sigmoid colon in 10 healthy controls and 10 patients with visceral pain due to the irritable bowel syndrome. The evoked brain potentials to 30 painful electrical stimuli from the sigmoid colon were recorded from 31 surface electrodes and subjected to electrical dipole source modelling. Two dipoles in the bilateral insular cortex, one dipole in the anterior cingulate gyrus and two dipoles in the bilateral second somatosensory area were found. The anterior cingulate dipole showed a more posterior position in patients than in control subjects. This finding suggests that the cortical representation of painful stimuli can be modified in presence of chronic visceral pain and that this change involves the anterior cingulate gyrus.

The aim of the study was to compare the cerebral generators following painful stimulation of the sigmoid colon and the abdominal skin in 11 healthy subjects. The evoked potentials (EPs) were recorded from 31 surface electrodes following painful electrical stimuli of the sigmoid colon, and of the referred pain area on the abdomen. Current dipole models estimating the EPs amplitude and topography were calculated. For colon stimulation, the earliest cortical activities were described by dipoles in the bilateral insula and in the anterior cingulate cortex, while both secondary somatosensory areas were activated later. When the skin was stimulated, early bilateral dipoles in the primary and secondary somatosensory areas were estimated, followed by a dipole in the frontal region. This suggests that painful cutaneous and visceral stimuli are processed differently in the brain.

Objective: To investigate possible neuroplastic changes induced by pain in cerebral areas devoted to nociceptive input processing., Methods: CO(2) laser-evoked potentials (LEPs) were recorded from 10 healthy subjects after stimulation of the right and left hand dorsum. Acute pain was obtained by topical application of capsaicin on the skin of right hand dorsum. LEPs were recorded after right and left hand stimulation before capsaicin, at the peak pain and 10-20 min after capsaicin removal. Right hand LEPs were evoked by laser stimuli delivered over the zone of secondary hyperalgesia during capsaicin and on both the zones of primary and secondary hyperalgesia after capsaicin removal., Results: After right hand stimulation, the vertex LEPs, which are generated in the cingulate cortex, were significantly decreased in amplitude during capsaicin application and after capsaicin removal. Moreover, the topography of these potentials was modified after capsaicin removal, shifting from the central toward the parietal region. Dipolar modelling showed that the dipolar source in the anterior cingulate cortex moved backward after capsaicin removal. All these changes were not observed after stimulation of the left hand, contralateral to the application of capsaicin, thus suggesting that functional changes are selective for the painful skin and the adjacent territories., Conclusions: Our results suggest that acute cutaneous pain may inhibit the neural activity in regions of central nervous system processing nociceptive inputs and cortical representation of these inputs can be rapidly modified in presence of acute pain.

This study aimed to evaluate whether painful cutaneous stimuli can affect specifically the excitability of the arm proximal muscle motor area. The motor evoked potentials (MEPs), recorded from the right biceps brachii muscle after either transcranial magnetic or electrical anodal stimulation of the left primary motor (MI) cortex, were conditioned by painful CO2 laser stimuli delivered either on the right hand dorsum or on the lateral surface of the right arm. Painful CO2 laser stimuli delivered on the hand skin reduced significantly the amplitude of MEPs evoked by the transcranial magnetic stimulation of the contralateral MI area, while the MEP amplitude was not significantly modified by CO2 laser pulses delivered on the arm skin. The inhibitory effect followed the arrival of the nociceptive inputs to the cerebral cortex. The amplitude of MEPs evoked by anodal electrical stimulation of the motor cortex was not decreased by conditioning painful stimuli delivered on the hand dorsum. Since the magnetic stimulation led to transynaptic activation of pyramidal neurons, while the anodal stimulation activated directly corticospinal axons, our findings suggest that CO2 laser pulses delivered on the hand are able to inhibit the arm proximal muscle motor area. [ABSTRACT FROM AUTHOR]