Katia Ricci

Pain in prolonged disorders of consciousness: Laser evoked potentials findings in patients with vegetative and minimally conscious states

Abstract Introduction: Pain perception is currently an open question in patients suffering from prolonged disorders of consciousness. The aim of the present study was to examine nociceptive specific laser evoked responses (LEPs) in view of long-latency evoked potentials by non-painful electrical stimuli (SEPs) and auditory mismatch negativity (MM). Methods: Three vegetative state (VS), four minimal Conscious State (MCS) patients and 11 age- and sex-matched controls were examined. Evoked responses were obtained by 64 scalp electrodes, stimulating the dorsum of the right hand by noxious laser and innocuous electrical stimulus, according to normal controls subjective rating. An auditory paradigm for MM was also employed. Results: The MM was present in all patients. The LEP vertex complex was recognizable in all cases, with a significant latency increase of both N2 and P2 which displayed changes of topographic representation. Late SEPs were absent in all patients except in one MCS case, who showed a significant N2 and P2 latency increase. Discussion: The results may suggest that high relevant stimuli may be processed even in patients with severe brain damage. Larger series and multimodal approaches may contribute to confirm that cortical arousal toward pain salience may be a primary function for life persistence.

Update on laser-evoked potential findings in fibromyalgia patients in light of clinical and skin biopsy features

Abstract In fibromyalgia (FM), reduced habituation of laser-evoked potentials (LEPs) suggests a dysfunction of pain processing at a central level. In this study, we aimed to further examine the nociceptive pathways at the peripheral to the central level in a large group of FM patients by means of LEPs and skin biopsy, in light of healthy controls findings and main clinical features. One hundred and ninety-nine FM patients and 109 age- and sex-matched controls were submitted to LEPs by the dorsum of the right hand and the skin over the right chest and knee tender point stimulation. Skin biopsy was performed in 21 randomly selected FM patients and 60 age- and sex-matched controls. The mean N2–P2 amplitude was reduced in the whole FM group, with normal or even increased values in patients with migraine as comorbidity and reduced values in other patients including those presenting with distal sensory deficits. All patients had reduced N2–P2 habituation in respect to controls. In the FM group, LEPs habituation was correlated with pain at tender points and bad quality of life. Epidermal fiber density was significantly reduced in FM patients versus controls, and correlated with N2–P2 amplitude by the hand and chest tender-point stimulation. Dysfunction in the nociceptive system at both the central and peripheral levels may concur to explain phenotypical eterogeneity and clinical symptom complexity in fibromyalgia.

Suggestion and Pain in Migraine: A Study by Laser Evoked Potentials

Belief and expectation are part of placebo effect. Migraine patients are characterized by a dysfunctional modulation of pain processing, though a clear placebo effect emerges in clinical trials. The aim of the study was to evaluate the effect of visual and verbal suggestion on subjective pain sensation and cortical responses evoked by CO2 painful laser stimuli in migraine without aura patients vs healthy controls. Twenty-six patients were recorded during the inter-ictal phase and compared to 26 sex and age-matched controls. The right hand and the right supraorbital zone were stimulated during a not conditioned and a conditioned task, where laser stimuli were delivered after a verbal and visual cues of decreased (D), increased (I) or basal (B) intensity, which was left unmodified during the entire task. In control subjects pain rating changed, according to the announced intensity, while in migraine patients the basal hyper-algesia remained unmodified. The N1 and N2 amplitudes tended to change coherently with the stimulus cue in controls, while an opposite paradoxical increase in decreasing condition emerged in migraine. The P2 amplitude modulation was also reduced in migraine, differently from controls. The altered pattern of pain rating and N2 amplitude modulation concurred with frequency of migraine, disability and allodynia. In controls suggestion influenced cortical pain processing and subjective pain rating, while in migraine a peculiar pattern of cortical activation contrasted external cues in order to maintain the basal hyper-algesia. This scarce influence of induced suggestion on pain experience seemed to characterize patients with more severe migraine and central sensitization.

Laser-evoked potential habituation and central sensitization symptoms in childhood migraine.

Objectives Few studies have addressed central sensitization symptoms and pain processing in childhood migraine. Our aims were to examine pain sensitivity and responses, including habituation, evoked by CO2 laser stimuli (laser-evoked potentials (LEPs)) in a cohort of children with migraine compared to non-migraine controls and to determine the correlation between LEP features and signs of central sensitization. Methods Thirty-five patients 8–15 years of age with migraines without aura were evaluated during the inter-critical phase and were compared to 17 controls. LEPs were analyzed, and their main features were correlated with clinical symptoms including allodynia and pericranial tenderness. Results The laser-evoked pain threshold was lower and the N2P2 vertex complex amplitude was higher in children with migraines. Furthermore, habituation of vertex waves of LEPs clearly showed a tendency toward progressive amplitude enhancement in the migraine group. Acute allodynia and inter-critical pericranial tenderness correlated with trigeminal LEP features, particularly with the abnormal habituation pattern. Discussion Abnormalities of pain processing and symptoms of central sensitization appear to be characteristics of children with migraine. Reduced habituation and progressive amplification of cortical responses to laser stimuli indicate an overactive nociceptive system at the onset of migraine, and this hyperactivity may subtend allodynia and pericranial tenderness. Future prospective trials may aid in the early identification of clinical phenotypes that display a tendency to develop into the chronic form of migraine, warranting a timely therapeutic approach.

Effects of anodal TDCS stimulation of left parietal cortex on visual spatial attention tasks in men and women across menstrual cycle.

Sex hormonal variations have been shown to affect functional cerebral asymmetries in cognitive domains, contributing to sex-related differences in functional cerebral organization. The aim of this study was to investigate spatial attention by means of a bisection line test and computer-supported attention task during the menstrual cycle in healthy women compared to men, in basal condition and under Transcranial Direct Current Stimulation (TDCS) of the left parietal cortex. Women were studied during the menses, follicular and luteal phases, ascertained by transvaginal ultrasounds. In basal conditions, women showed a clear deviation toward the right in the bisection line test during the menstrual phase, similarly to men. The midpoint recognition in the computer-supported attention task was not influenced by the menstrual cycle for women, while men showed a significant increase in errors toward the left side. The anodal activation of the left parietal cortex did not affect the line bisection task, while in men it reduced the total amount of errors in midpoint recognition observed in the computer supported attention task. The hand-use effect demonstrated by the bisection-line test could be influenced by estrogen fluctuations, while the right hemisphere prevalence in spatial attention appears to be gender-related and scarcely influenced by the menstrual cycle. The left parietal cortex seems to exert a scarce effect on hand-use effect, while its activation is able to revert sex related right hemisphere supremacy.

Age‐related changes in laser‐evoked potentials following trigeminal and hand stimulation in healthy subjects

This study aimed to evaluate age‐related changes in laser‐evoked potential (LEP) features, including habituation, via trigeminal and hand stimulation in a large group of healthy volunteers.

Effects of OnabotulintoxinA on Habituation of Laser Evoked Responses in Chronic Migraine

Onabotulintoxin A (BontA) is an efficacious preventive treatment for chronic migraine, though the specific mechanism of action is still under discussion. The study aims: (1) To evaluate pain processing modifications in chronic migraine patients (CM) under single BontA administration in pericranial muscles, by means of CO2 Laser Evoked Potentials (LEPs) obtained by the stimulation of the skin over the right frontal and trapezius injection sites and hand dorsum, in a double blind placebo controlled crossover design. (2) To correlate main LEPs findings with clinical outcome after one year of BontA treatment. Twenty refractory CM patients were included in the analysis. The LEPs were recorded in basal conditions and seven days after BontA (PREEMPT protocol) and saline solution injection. The N1, N2 and P2 amplitude and latencies and N2P2 habituation index were evaluated and correlated with the percent change of headache frequency after one year of toxin treatment. After seven days of BontA treatment, a normalization of the trigeminal habituation index was observed, which was correlated with the clinical outcome after one year of BontA therapy. Patients displaying trigeminal LEPs facilitation at T0 time showed a more efficient therapeutic outcome. Neurotoxin may exert a modulating effect on trigeminal nociception, normalizing central neurotransmission.

Effects of left primary motor and dorsolateral prefrontal cortex transcranial direct current stimulation on laser-evoked potentials in migraine patients and normal subjects.

Migraine is characterized by an altered cortical excitability. Because transcranial direct current stimulation (tDCS) can change brain activity noninvasively, it is possible to hypothesize its efficacy in modulating pain in migraine. In this study, we compared the effects of tDCS of the left primary motor cortex (M1) and left dorsolateral prefrontal cortex (DLPFC) both on subjective pain and on evoked responses induced by laser stimulation (LEPs). Thirty-two patients and sixteen controls were randomized to receive sham stimulation and real tDCS with the anode centered over M1 or DLPFC. Laser Evoked potentials were recorded in basal, sham and tDCS conditions. We did not find significant acute changes in LEPs parameters and pain perception among subjects who received tDCS of both M1 and DLPFC. After DLPFC tDCS, we observed a significant increase of N2-P2 component habituation in migraine patients while M1 stimulation reduced it. These findings may suggest a modulation of abnormal pain processing induced by DLPFC and M1 anodal tDCS and outline the need for future investigations exploring the possible neuronal plasticity changes supporting the clinical effect on migraine.

Laser Evoked Potentials in Early and Presymptomatic Huntington's Disease.

Pain was rarely studied in Huntingtons disease (HD). We presently aimed to extend our previous study on pain pathways functions by laser evoked potentials (LEPs) to a larger cohort of early unmedicated HD patients and a small group of presymptomatic HD (PHD) subjects. Forty-two early HD patients, 10 PHD patients, and 64 controls were submitted to LEPs by right-hand stimulation. Two series of 30 laser stimuli were delivered, and artifact-free responses were averaged. The N1, N2, and P2 latencies were significantly increased and the N2P2 amplitude significantly reduced in HD patients compared to controls. In the HD group, the LEPs abnormalities correlated with functional decline. PHD subjects showed a slight and insignificant increase in LEPs latencies, which was inversely correlated with the possible age of HD clinical onset. Data of the present study seem to suggest that the functional state of nociceptive pathways as assessed by LEPs may be a potential biomarker of disease onset and progression. The assessment of pain symptoms in premanifest and manifest HD may also open a new scenario in terms of subtle disturbances of pain processing, which may have a role in the global burden of the disease.

Functional Connectivity of EEG Signals Under Laser Stimulation in Migraine

In previous studies, migraine patients showed abnormalities in pain-related evoked responses, as reduced habituation to repetitive stimulation. In this study, we aimed to apply a novel analysis of EEG bands synchronization and directed dynamical influences under painful stimuli in migraine patients compared to non-migraine healthy volunteers. Thirty-one migraine without aura outpatients (MIGR) were evaluated and compared to 19 controls (CONT). The right hand was stimulated by means of 30 consecutive CO2 laser stimuli. EEG signal was examined by means of Morlet wavelet, synchronization entropy (SE), and Granger causality (GC), and the statistically validated results were mapped on the corresponding scalp locations. The vertex complex of averaged laser-evoked responses (LEPs) showed reduced habituation compared to CONT. In the prestimulus phase, enhanced SE in the 0, 5–30 Hz range was present in MIGR and CONT between the bilateral temporal–parietal and the frontal regions around the midline. Migraine patients showed an anticipation of EEG changes preceding the painful stimulation compared to CONT. In the poststimulus phase, the same cortical areas were more connected in MIGR vs CONT. In both groups of patients and CONT, the habituation index was negatively correlated with the GC scores. A different pattern of cortical activation after painful stimulation was present in migraine. The increase in cortical connections during repetitive painful stimulation may subtend the phenomenon of LEPs reduced habituation. Brain network analysis may give an aid in understanding subtle changes of pain processing under laser stimuli in migraine patients.