Baseline robot-measured kinematic metrics predict discharge rehabilitation outcomes in individuals with subacute stroke.

Background: The literature on upper limb robot-assisted therapy showed that robot-measured metrics can simultaneously predict registered clinical outcomes. However, only a limited number of studies correlated pre-treatment kinematics with discharge motor recovery. Given the importance of predicting rehabilitation outcomes for optimizing physical therapy, a predictive model for motor recovery that incorporates multidirectional indicators of a patient's upper limb abilities is needed. Objective: The aim of this study was to develop a predictive model for rehabilitation outcome at discharge (i.e., muscle strength assessed by the Motricity Index of the affected upper limb) based on multidirectional 2D robot-measured kinematics. Methods: Re-analysis of data from 66 subjects with subacute stroke who underwent upper limb robot-assisted therapy with an end-effector robot was performed. Two least squares error multiple linear regression models for outcome prediction were developed and differ in terms of validation procedure: the Split Sample Validation (SSV) model and the Leave-One-Out Cross-Validation (LOOCV) model. In both models, the outputs were the discharge Motricity Index of the affected upper limb and its sub-items assessing elbow flexion and shoulder abduction, while the inputs were the admission robot-measured metrics. Results: The extracted robot-measured features explained the 54% and 71% of the variance in clinical scores at discharge in the SSV and LOOCV validation procedures respectively. Normalized errors ranged from 22% to 35% in the SSV models and from 20% to 24% in the LOOCV models. In all models, the movement path error of the trajectories characterized by elbow flexion and shoulder extension was the significant predictor, and all correlations were significant. Conclusion: This study highlights that motor patterns assessed with multidirectional 2D robot-measured metrics are able to predict clinical evalutation of upper limb muscle strength and may be useful for clinicians to assess, manage, and program a more specific and appropriate rehabilitation in subacute stroke patients.

Effect of balance training using virtual reality-based serious games in individuals with total knee replacement: A randomized controlled trial.

BACKGROUND: Virtual reality (VR) and serious games (SGs) are widespread in rehabilitation for many orthopedic and neurological diseases. However, few studies have addressed the effects of rehabilitation with VR-based SGs on clinical, gait, and postural outcomes in individuals with total knee replacement (TKR). OBJECTIVE: The primary objective was the efficacy of balance training using non-immersive VR-based SGs compared to conventional therapy in TKR patients on the Time Up and Go test. Secondary objectives included the efficacy on clinical, gait, and postural outcomes. METHODS: We randomly allocated 56 individuals with unilateral TKR to the experimental group (EG) or control group (CG) for 15 sessions (45 min; 5 times per week) of non-immersive VR-based SGs or conventional balance training, respectively. The primary outcome was functional mobility measured by the Timed Up and Go test; secondary outcomes were walking speed, pain intensity, lower-limb muscular strength, independence in activities of daily living as well as gait and postural parameters. RESULTS: We found significant within-group differences in all clinical outcomes and in a subset of gait (p<0.0001) and postural (p ≤ 0.05) parameters. Analysis of the stance time of the affected limb revealed significant between-group differences (p = 0.022): post-hoc analysis revealed within-group differences in the EG (p = 0.002) but not CG (p = 0.834). We found no significant between-group differences in other outcomes. CONCLUSIONS: Balance training with non-immersive VR-based SGs can improve clinical, gait, and postural outcomes in TKR patients. It was not superior to the CG findings but could be considered an alternative to the conventional approach and can be added to a regular rehabilitation program in TKR patients. The EG had a more physiological duration of the gait stance phase at the end of the treatment than the CG. CLINICALTRIALS: GOV: NCT03454256.

Gait Recovery with an Overground Powered Exoskeleton: A Randomized Controlled Trial on Subacute Stroke Subjects.

BACKGROUND: Overground Robot-Assisted Gait Training (o-RAGT) provides intensive gait rehabilitation. This study investigated the efficacy of o-RAGT in subacute stroke subjects, compared to conventional gait training. METHODS: A multicenter randomized controlled trial was conducted on 75 subacute stroke subjects (38 in the Experimental Group (EG) and 37 in the Control Group (CG)). Both groups received 15 sessions of gait training (5 sessions/week for 60 min) and daily conventional rehabilitation. The subjects were assessed at the beginning (T1) and end (T2) of the training period with the primary outcome of a 6 Minutes Walking Test (6MWT), the Modified Ashworth Scale of the Affected lower Limb (MAS-AL), the Motricity Index of the Affected lower Limb (MI-AL), the Trunk Control Test (TCT), Functional Ambulation Classification (FAC), a 10 Meters Walking Test (10MWT), the modified Barthel Index (mBI), and the Walking Handicap Scale (WHS). RESULTS: The 6MWT increased in both groups, which was confirmed by both frequentist and Bayesian analyses. Similar outcomes were registered in the MI-AL, 10MWT, mBI, and MAS-AL. The FAC and WHS showed a significant number of subjects improving in functional and community ambulation in both groups at T2. CONCLUSIONS: The clinical effects of o-RAGT were similar to conventional gait training in subacute stroke subjects. The results obtained in this study are encouraging and suggest future clinical trials on the topic.

Factors Influencing Functional Outcome at Discharge: A Retrospective Study on a Large Sample of Patients Admitted to an Intensive Rehabilitation Unit.

OBJECTIVE: Functional outcome represents the most central objective of rehabilitation programs. Understanding which factors could affect functional status at discharge is crucial for the planning of appropriate treatments in both neurologic and orthopedic patients. The aim of this study was to investigate which clinical and demographic variables, collected at the patient's admission, could influence the functional outcome, assessed by the modified Barthel Index (mBI), at discharge. DESIGN: A retrospective study was conducted on a large cohort (n = 3548) of orthopedic and neurologic patients. Functional, demographic, and clinical records at patient admission and mBI score at discharge were collected. General linear model analysis was performed to assess the influence of these variables on functional outcome at discharge. RESULTS: The results reported a significant effect of mBI score at admission (P < 0.0001), age (P < 0.0001), and time from the acute event (P < 0.0001) on mBI score at discharge. Moreover, the disease type (neurologic or orthopedic) adjusted by sex (male or female) and presence of different impairments (cognitive and behavioral impairments) and complications (hypertension and cardiovascular diseases) significantly influenced mBI score at discharge (P < 0.05) (R2 = 0.497). No significant interactions between other factors were found (P > 0.05). CONCLUSION: Several prognostic factors should be considered when planning an appropriate tailored rehabilitation program.

Ultrasound guidance increases diagnostic yield of needle EMG in plegic muscle.

OBJECTIVES: To increase the specificity of motor unit potential (MUPs) detection by using ultrasound guided electromyography (USG-EMG) in patients with muscle plegia due to traumatic nerve lesions. METHODS: Forty-six patients with recent nerve trauma underwent baseline standard EMG (ST-EMG) evaluation with evidence of absent MUPs. In 41 of them, ST-EMG was repeated after 2-3 months (T1) and the patients were accordingly divided in two groups: ST-EMG+ (if MUPs were detected) or ST-EMG- (MUPs not detected). Then, ST-EMG- patients underwent muscle ultrasound evaluation (M-US) and, if isles of muscular contractility were found, they also had USG-EMG. The same protocol was repeated 4-6 months after baseline (T2). RESULTS: At T1, 22/41 patients were ST-EMG+. While 19/41 were ST-EMG-; 9 of these patients had M-US consistent with residual muscular activity, for that reasons underwent USG-EMG with 7 of 9 demonstrating MUPs (at T2 all of these 7 patients resulted ST-EMG). In the other 2 patients, we found no MUPs at T1 but they became ST-EMG+ or USG-EMG positive at T2. The remaining 10 ST-EMG- patients had no EMG or US evidence of muscle contraction at T1, but at T2 2 of 10 became ST-EMG+ and 2 had USG-EMG showing MUPs. In the remaining 6 patients still M-US negative at T2, complete denervation was diagnosed. Concerning the 22 patients who were ST-EMG+ at T1, all but one showed increase of MUPs at T2. CONCLUSIONS: In this study, we demonstrated the utility of US guidance when performing EMG evaluation in locating isles of muscular contractility in patients who have no detectable MUPs on EMG after nerve trauma. SIGNIFICANCE: USG-EMG significantly increases the specificity of needle EMG allowing earlier detection of MUPs.

Abnormal Circadian Modification of Aδ-Fiber Pathway Excitability in Idiopathic Restless Legs Syndrome.

Restless legs syndrome (RLS) is characterized by unpleasant sensations generally localized to legs, associated with an urge to move. A likely pathogenetic mechanism is a central dopaminergic dysfunction. The exact role of pain system is unclear. The purpose of the study was to investigate the nociceptive pathways in idiopathic RLS patients. We enrolled 11 patients (mean age 53.2 ± 19.7 years; 7 men) suffering from severe, primary RLS. We recorded scalp laser-evoked potentials (LEPs) to stimulation of different sites (hands and feet) and during two different time conditions (daytime and nighttime). Finally, we compared the results with a matched control group of healthy subjects. The Aδ responses obtained from patients did not differ from those recorded from control subjects. However, the N1 and the N2-P2 amplitudes' night/day ratios after foot stimulation were increased in patients, as compared to controls (N1: patients: 133.91 ± 50.42%; controls: 83.74 ± 34.45%; p = 0.016; Aδ-N2-P2: patients: 119.15 ± 15.56%; controls: 88.42 ± 23.41%; p = 0.003). These results suggest that RLS patients present circadian modifications in the pain system, which are not present in healthy controls. Both sensory-discriminative and affective-emotional components of pain experience show parallel changes. This study confirms the structural integrity of Aδ nociceptive system in idiopathic RLS, but it also suggests that RLS patients present circadian modifications in the pain system. These findings could potentially help clinicians and contribute to identify new therapeutic approaches.

Clinical effects of robot-assisted gait training and treadmill training for Parkinson's disease. A randomized controlled trial.

BACKGROUND: Although gait disorders strongly contribute to perceived disability in people with Parkinson's disease, clinical trials have failed to identify which task-oriented gait training method can provide the best benefit. Freezing of gait remains one of the least investigated and most troublesome symptoms. OBJECTIVE: We aimed to compare the effects of robot-assisted gait training and treadmill training on endurance and gait capacity in people with Parkinson disease; the secondary aim was to compare the effect of the treatments in people with freezing and/or severe gait disability and assess changes in overall disease-related disability and quality of life. METHODS: Outpatients with Parkinson disease (Hoehn and Yahr stage≥2) were randomly assigned to receive 20 sessions of 45-min gait training assisted by an end-effector robotic device (G-EO System) or treadmill training. Outcome assessments were the 6-min walk test, Timed Up and Go test, Freezing of Gait Questionnaire, Unified Parkinson's Disease Rating Scales and Parkinson's Disease Quality of Life Questionnaire-39 administered before (T0) and after treatment (T1). RESULTS: We included 96 individuals with Parkinson disease: 48 with robot-assisted gait training and 48 treadmill training. Both groups showed significant improvement in all outcomes. As compared with baseline, with robot-assisted gait training and treadmill training, endurance and gait capacity were enhanced by 18% and 12%, respectively, and motor symptoms and quality of life were improved by 17% and 15%. The maximum advantage was observed with the Freezing of Gait Questionnaire score, which decreased by 20% after either treatment. On post-hoc analysis, dependent walkers benefited more than independent walkers from any gait training, whereas freezers gained more from robot-assisted than treadmill training in terms of freezing reduction. CONCLUSIONS: Repetitive intensive gait training is an effective treatment for people with Parkinson disease and can increase endurance and gait velocity, especially for those with severe walking disability. Advantages are greater with robot-assisted gait training than treadmill training for individuals with freezing of gait - related disability.

Cortical inhibition of laser pain and laser-evoked potentials by non-nociceptive somatosensory input.

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.

Effects of robot assisted gait training in progressive supranuclear palsy (PSP): a preliminary report.

BACKGROUND AND PURPOSE: Progressive supranuclear palsy (PSP) is a rare neurodegenerative disease clinically characterized by prominent axial extrapyramidal motor symptoms with frequent falls. Over the last years the introduction of robotic technologies to recover lower limb function has been greatly employed in the rehabilitative practice. This observational trial is aimed at investigating the changes in the main spatiotemporal following end-effector robot training in people with PSP. METHOD: Pilot observational trial. PARTICIPANTS: Five cognitively intact participants with PSP and gait disorders. INTERVENTIONS: Patients were submitted to a rehabilitative program of robot-assisted walking sessions for 45 min, 5 times a week for 4 weeks. MAIN OUTCOME MEASURES: The spatiotemporal parameters at the beginning (T0) and at the end of treatment (T1) were recorded by a gait analysis laboratory. RESULTS: Robot training was feasible, acceptable and safe and all participants completed the prescribed training sessions. All patients showed an improvement in the gait spatiotemporal index (Mean velocity, Cadence, Step length, and Step width) (T0 vs. T1). CONCLUSIONS: Robot training is a feasible and safe form of rehabilitation for cognitively intact people with PSP. The lack of side effects and the positive results in the gait parameter index in all patients support the recommendation to extend the trials of this treatment. Further investigation regarding the effectiveness of robot training in time is necessary. TRIAL REGISTRATION: ClinicalTrials.gov NCT01668407.

Robot-assisted walking training for individuals with Parkinson's disease: a pilot randomized controlled trial.

BACKGROUND: Over the last years, the introduction of robotic technologies into Parkinson's disease rehabilitation settings has progressed from concept to reality. However, the benefit of robotic training remains elusive. This pilot randomized controlled observer trial is aimed at investigating the feasibility, the effectiveness and the efficacy of new end-effector robot training in people with mild Parkinson's disease. METHODS: Design. Pilot randomized controlled trial. RESULTS: Robot training was feasible, acceptable, safe, and the participants completed 100% of the prescribed training sessions. A statistically significant improvement in gait index was found in favour of the EG (T0 versus T1). In particular, the statistical analysis of primary outcome (gait speed) using the Friedman test showed statistically significant improvements for the EG (p = 0,0195). The statistical analysis performed by Friedman test of Step length left (p = 0,0195) and right (p = 0,0195) and Stride length left (p = 0,0078) and right (p = 0,0195) showed a significant statistical gain. No statistically significant improvements on the CG were found. CONCLUSIONS: Robot training is a feasible and safe form of rehabilitative exercise for cognitively intact people with mild PD. This original approach can contribute to increase a short time lower limb motor recovery in idiopathic PD patients. The focus on the gait recovery is a further characteristic that makes this research relevant to clinical practice. On the whole, the simplicity of treatment, the lack of side effects, and the positive results from patients support the recommendation to extend the use of this treatment. Further investigation regarding the long-time effectiveness of robot training is warranted. TRIAL REGISTRATION: ClinicalTrials.gov NCT01668407.

Habituation to pain in "medication overuse headache": a CO2 laser-evoked potential study.

OBJECTIVE: Our aim was to investigate CO(2) laser-evoked potential (LEP) habituation to experimental pain in a group of patients affected by medication-overuse headache, with a history of episodic migraine becoming chronic, before and after treatment, consisting in acute medication withdrawal and a preventive treatment cycle. BACKGROUND: One of the main features of LEPs in migraineurs is a lower habituation to repetitive noxious stimuli during the interictal phase. METHODS: LEPs were recorded to stimulation of both the right hand and the right perioral region in 14 patients and in 14 healthy subjects. The habituation of both the N1 and the vertex N2/P2 components was assessed by measuring the LEP amplitude changes across 3 consecutive repetitions of 30 trials each. RESULTS: In the 8 patients who had clinically improved after treatment, the N2/P2 amplitude habituation was significantly higher after treatment than before treatment following both hand (F = 43.2, P < .0001) and face stimulation (F = 6.9, P = .01). In these patients, the N2/P2 amplitude habituation after treatment was not different from that obtained in healthy controls (P = .18 and P = .73 for hand and face stimulation, respectively). On the contrary, in the patients who did not improve, the N2/P2 amplitude still showed reduced habituation after both hand (F = 3.1, P = .08) and face (F = 0.7, P = .4) stimulation. CONCLUSION: The deficient habituation of the vertex N2/P2 complex was partly restored after successful treatment of medication-overuse headache, reflecting a modification in pain-processing pathways.

Mechanisms of neuropathic pain in patients with Charcot-Marie-Tooth 1 A: a laser-evoked potential study.

Charcot-Marie-Tooth (CMT) disease is the most common inherited neuropathy. The CMT1A type can be considered the typical phenotype of this disease. Although pain is not considered a relevant symptom in CMT patients by physicians and no study assessed it comprehensively, this symptom is frequently complained by patients. The objective of the present study was to investigate the nociceptive system in a sample of CMT1A patients suffering from pain by laser-evoked potentials (LEPs). Moreover, we also used a pain specific questionnaire in order to obtain patient-oriented data about their painful symptoms, the Neuropathic Pain Diagnostic Questionnaire (DN4). We evaluated 16 patients affected by CMT1A and 14 controls. All subjects underwent a standard LEP recording session (foot, hand, and face stimulation) and filled in the DN4. While the N2/P2 amplitude to foot stimulation was lower in CMT patients than in controls (p=0.003), no difference in LEP amplitude to both hand and face stimulation was found between patients and healthy subjects (p>0.05). This result is probably due to a length-dependent Adelta-fiber loss which involves mostly the longer fibers coming from the lower limb. In our patients, there was a significant association between a reduced N2/P2 amplitude to foot stimulation and a high DN4 score (p=0.03), meaning that patients with highly probable neuropathic pain had also low N2/P2 amplitude values to painful foot stimulation. This suggests that in our CMT1A patients neuropathic pain is probably related to a reduction of the Adelta afferents.

Laser evoked potential recording from intracerebral deep electrodes.

OBJECTIVE: To investigate whether recording from deep intracerebral (IC) electrodes can disclose laser evoked potential (LEP) components generated under the cerebral cortex. METHODS: LEPs were recorded to hand and/or perioral region stimulation from 7 patients suffering from Parkinson's disease, who underwent implant of IC electrodes in the globus pallidum pars interna (GPi), in the subthalamic nucleus (STN) and in the pedunculopontine nucleus (PPN). LEPs were obtained from the IC electrode contacts and from the Cz vertex, referred to the nose. RESULTS: The scalp traces showed a triphasic response (P1-N2-P2). The IC electrodes recorded two main components (ICP2 and ICN2), showing the same latencies as the scalp N2 and P2 potentials, respectively. The ICP2-ICN2 complex was sometimes preceded by a ICP1 wave at the same latency of the scalp P1 response. CONCLUSIONS: The LEP components recorded from the IC electrodes mirrored the ones picked up from the Cz lead, thus suggesting that they are probably generated by the opposite pole of the same cortical sources producing the scalp responses. SIGNIFICANCE: In the IC traces, there was no evidence of earlier potentials possibly generated within the thalamus or of subcortical far-field responses. This means that the nociceptive signal amplification occurring within the cerebral cortex is necessary to produce identifiable LEP components.

Learning potentiates neurophysiological and behavioral placebo analgesic responses.

Expectation and conditioning are supposed to be the two main psychological mechanisms for inducing a placebo response. Here, we further investigate the effects of both expectation, which was induced by verbal suggestion alone, and conditioning at the level of N1 and N2-P2 components of CO2 laser-evoked potentials (LEPs) and subjective pain reports. Forty-four healthy volunteers were pseudorandomly assigned to one of three experimental groups: Group 1 was tested with verbal suggestion alone, Group 2 was tested with a conditioning procedure, whereby the intensity of painful stimulation was reduced surreptitiously, so as to make the volunteers believe that the treatment was effective, Group 3 was a control group that allowed us to rule out phenomena of sensitization and/or habituation. Pain perception was assessed according to a Numerical Rating Scale (NRS) ranging from 0=no pain sensation to 10=maximum imaginable pain. Both verbal suggestions (Group 1) and conditioning (Group 2) modified the N2-P2 complex, but not the N1 component of LEPs. However, the suggestion-induced LEP changes occurred without subjective perception of pain decrease. Conversely, the N2-P2 amplitude changes that were induced by the conditioning procedure were associated with the subjective perception of pain reduction. Compared to natural history, conditioning produced more robust reductions of LEP amplitudes than verbal suggestions alone. Overall, these findings indicate that prior positive experience plays a key role in maximizing both behavioral and neurophysiological placebo responses, emphasizing that the placebo effect is a learning phenomenon which affects the early central nociceptive processing.

Spinal cord stimulation normalizes abnormal cortical pain processing in patients with cardiac syndrome X.

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.

Pre-stimulus alpha power affects vertex N2-P2 potentials evoked by noxious stimuli.

It is well known that scalp potentials evoked by nonpainful visual and auditory stimuli are enhanced in amplitude when preceded by pre-stimulus low-amplitude alpha rhythms. This study tested the hypothesis that the same holds for the amplitude of vertex N2-P2 potentials evoked by brief noxious laser stimuli, an issue of interest for clinical perspective. EEG data were recorded in 10 subjects from 30 electrodes during laser noxious stimulation. The artifact-free vertex N2-P2 complex was spatially enhanced by surface Laplacian transformation. Pre-stimulus alpha power was computed at three alpha sub-bands according to subject's individual alpha frequency peak (i.e. about 6-8Hz for alpha 1, 8-10Hz for alpha 2 and 10-12Hz for alpha 3 sub-band). Individual EEG single trials were divided in two sub-groups. The strong-alpha sub-group (high band power) included halfway of all EEG single trials, namely those having the highest pre-stimulus alpha power. Weak-alpha sub-group (low band power) included the remaining trials. Averaging procedure provided laser evoked potentials for both trial sub-groups. No significant effect was found for alpha 1 and alpha 2 sub-bands. Conversely, compared to strong-alpha 3 sub-group, weak-alpha 3 sub-group showed vertex N2-P2 potentials having significantly higher amplitude (p<0.05). These results extend to the later phases of pain processing systems the notion that generation mechanisms of pre-stimulus alpha rhythms and (laser) evoked potentials are intrinsically related and subjected to fluctuating "noise". That "noise" could explain the trial-by-trial variability of laser evoked potentials and perception.

Seeing the pain of others while being in pain: a laser-evoked potentials study.

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.

Nociceptive contribution to the evoked potentials after painful intramuscular electrical stimulation.

Our study aimed at investigating the nociceptive contribution to the somatosensory evoked potentials after electrical intramuscular stimulation (mSEPs) at painful intensity. Scalp mSEPs were recorded in 10 healthy subjects after electrical stimulation of the left brachioradialis muscle at three intensities: non-painful (I2), slightly painful (I4) and moderately painful (I6). For each intensity, mSEPs were recorded in a neutral condition (NC) in which subjects did not have any task, and in an attention condition (AC) in which subjects were asked to count the number of stimuli. In both NC and AC, the N120 and P220 amplitudes were significantly higher at I6 than at I2. While the N120 amplitude did not vary between NC and AC, the P220 amplitude was significantly higher in AC than in NC at all stimulus intensities. Our results suggest that nociceptive inputs contribute to the N120 amplitude increase at painful stimulus intensity, while the P220 amplitude is more sensitive to changes of subjects' attention level. Therefore, the N120 amplitude increase to moderately painful stimuli, as compared to non-painful stimuli, may represent a marker of the activation of the muscular thin myelinated afferents.

Abnormal processing of the nociceptive input in Parkinson's disease: a study with CO2 laser evoked potentials.

Since a number of patients with Parkinson's Disease (PD) complain of painful sensations, we studied whether the central processing of nociceptive inputs is abnormal in PD. To test this hypothesis, we recorded scalp CO(2) laser evoked potentials (LEPs) to hand skin stimulation in 18 pain-free PD patients with unilateral bradykinetic-rigid syndrome (hemiparkinson) during the off state and in 18 healthy subjects. This technique allows us to explore non-invasively the functional status of some cerebral structures involved in nociceptive input processing. In both PD patients and control subjects, CO(2) laser stimulation gave rise to a main negative N2 potential followed by a positive P2 response at vertex peaking at a latency of about 200 and 300ms, respectively. These potentials are thought to originate from several brain structures devoted to nociceptive input processing, including the cingulate gyrus and insula. PD patients and normal subjects showed comparable N2 and P2 latencies, whereas the N2/P2 peak-to-peak amplitude was significantly lower in PD patients (regardless of the clinically affected body side) than in controls. LEPs were even recorded after acute L-dopa administration in 7 additional PD patients. L-dopa administration yielded no significant change in N2/P2 amplitude as compared to the off state. These results suggest an abnormal nociceptive input processing in pain-free PD patients which appears to be independent of clinical expression of parkinsonian motor signs and is not affected by dopaminergic stimulation.

Sumatriptan fast-disintegrating/rapid-release tablets in the acute treatment of migraine.

Sumatriptan is the first serotonin (5-hydroxytryptamine [5-HT](1B/1D)) receptor agonist specifically designed for the acute treatment of migraine. A new sumatriptan fast disintegrating/rapid release tablet (FDT/RRT) using RT technology has been developed to enhance tablet disintegration and dispersion in the stomach with the intention of speeding absorption and onset of effect, hence mitigating the effects on the gastrointestinal dysmotility that typically accompanies the attack. Sumatriptan FDT/RRT is bioequivalent to conventional tablets, although it provides slightly faster absorption during early post-dose interval. Clinical trials indicate that sumatriptan FDT/RRT is rapidly effective in terms of freedom from pain and return to normal activities, both with early and late treatment. The drug is well tolerated. In an oral formulation, which is the patients' preferred dosing route, sumatriptan FDT/RRT may therefore constitute an advance in the management of acute migraine attacks.