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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.

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.

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.

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.

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.

Objective: To investigate the possible presence of multiple spino-thalamic pathways with different conduction velocities (CVs) in the human spinal cord., Methods: Laser evoked potentials (LEPs) were recorded in 10 healthy subjects after stimulation of the dorsal midline at four vertebral level: C5, T2, T6, and T10. This method allowed us to minimize the influence of the conduction in the peripheral fibers and to calculate the spinal CV in two different ways: (1) the reciprocal of the slope of the regression line was obtained from the latencies of the different LEP components, and (2) the distance between C5 and T10 was divided by the latency difference of the responses at the two sites. In particular, we considered the middle-latency N1 potential (latencies of around 135, 150, 157, and 171 ms after stimulation at C5, T2, T6, and T10 levels, respectively), which is generated in the second somatosensory (SII) area, and the late P2 response (latencies of around 336, 344, 346, and 362 ms after stimulation at C5, T2, T6, and T10 levels, respectively), which is generated in the anterior cingulate cortex (ACC)., Results: The calculated CV of the spinal fibers generating the N1 potential (around 9 m/s) was significantly different (P<0.05) from the one of the pathway producing the P2 response (around 13 m/s)., Conclusions: Our results suggest that the N1 and the P2 LEP components are generated by two parallel spinal pathways., Significance: Both the N1 and P2 potentials should be recorded in the clinical routine since a dissociated abnormality of either response may be found in lesions of the nociceptive system not only in the brain, but also at spinal cord level.

The oesophagus, stomach, duodenum and sigmoid colon were electrically stimulated in 12 healthy volunteers with a thin nasal endoscope. The painful cortical evoked potentials (EPs) were recorded from 64 surface electrodes. The early EPs with latencies < 200 ms were studied and the corresponding dipole sources were calculated. The electrical current intensities needed to evoke pain were highest in the stomach and duodenum, compared to the other segments (F = 7.8; P < 0.001; post hoc analysis P < 0.05). The EP latencies after stimulation of the stomach and sigmoid colon were shorter compared with those to stimulation of the oesophagus and duodenum (all P values < 0.001). The EP amplitudes were higher to oesophagus stimulation (all P values < 0.001 except for the early positivity). The potential fields obtained after stimulation of the most distal segments (duodenum and sigmoid colon) were in general distributed more posteriorly compared to those recorded in the more proximal regions. The EP topographies to stimulation of all gut tracts were explained by a bilateral source in the second somatosensory (SII) area, by a dipole in the anterior cingulate cortex (ACC), and by a bilateral generator in the insular cortex. However, the position of the sources significantly changed depending on the stimulated gut tract. Moreover, while the SII and ACC sources were initially activated to oesophagus and stomach stimulation, the ACC and insular activities were the earliest ones after stimulation of the lower gut segments. The findings reflect differences in pathways and brain processing of visceral nociceptive inputs coming from either upper or lower gut and may improve our understanding of the brain-gut axis in health and disease.

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 evaluate the effect of tonic pain evoked by topical application of capsaicin on the somatosensory sensation of warmth. The warmth pathways were studied in ten healthy subjects by recording the scalp potentials evoked by non-painful warm laser stimuli delivered on both the right and left perioral region (warmth C-fiber related laser-evoked potentials (C-LEPs)). Tonic pain was induced by topical capsaicin application above the lateral part of the right upper lip. The area of primary and secondary hyperalgesia were mapped. C-LEPs were obtained from 31 scalp electrodes before, during, and after capsaicin application. C-LEPs from the right perioral region were evoked by laser stimuli delivered to the area of secondary hyperalgesia during capsaicin application and on both the areas of primary and secondary hyperalgesia after capsaicin removal. While the lateralized N1/P1 component (around 185 ms of latency) was not affected by the capsaicin, the amplitudes of the later vertex C-LEPs (around 260 and 410 ms of latency for the N2a and P2 potentials, respectively) evoked from the secondary hyperalgesic area on the right side and from a symmetrical non-hyperalgesic area on the left perioral region were significantly decreased during capsaicin application and after capsaicin removal, as compared with the baseline recordings. At the same times, the rating of the laser-evoked warmth sensation was reduced significantly. This inhibitory effect can occur at brainstem level and is possibly due to: 1) trigemino-cortico-trigeminal circuits, similar to those mediating the classical diffuse noxious inhibitory control, or 2) an increased background activity of the capsaicin-insensitive A-fibers, which mediate the secondary hyperalgesia. Probably due to a peripheral inhibitory mechanism, neither reliable C-LEP components nor warmth sensation were evoked by laser pulses delivered to the primary hyperalgesic area. This is the first neurophysiological evidence in humans of an inhibitory effect of pain on warmth sensation.

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 the possible contribution of the primary somatosensory area (SI) to pain sensation., Methods: Depth recordings of CO2 laser evoked potentials (LEPs) and somatosensory evoked potentials (SEPs) were performed in an epileptic patient with a stereotactically implanted electrode (Talairach coordinates y=-23, z=40) that passed about 10 mm below the hand representation in her left SI area, as assessed by the source of the N20 SEP component., Results: The intracerebral electrode was able to record the N20 SEP component after non-painful electrical stimulation of her right median nerve. The N20 potential showed a phase reversal in the bipolar montage (at about 31 mm from the midline), which confirms that the electrode was located near its generator in area 3b. In contrast, no reliable response was recorded from the SI electrode after painful CO2 laser stimulation of the right hand. An N2-P2 response was evoked at the vertex electrode (Cz), thus demonstrating the effectiveness of the delivered CO2 laser stimuli., Conclusions: Since the N20 SEP component originates from the anterior bank of the post-central gyrus (area 3b), our result suggests that this part of SI does not participate in LEP generation. In fact, the previously published LEP sources in the SI area estimated from scalp recordings are about 10-17 mm posterior of the electrode in our patient, suggesting that they are more likely located in area 1, 2 or posterior parietal cortex.

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.

Pain is a complex multi-dimensional phenomenon that influences a wide variety of nervous system functions, including sensory--discriminative, affective--motivational and cognitive--evaluative components. So far, these components have been studied in both patients with chronic pain and in normal subjects in whom pain was induced experimentally. The interaction between pain and motor function is not fully understood, although from everyday life it is known that pain affects movements. The effects of pain on motor control are typically seen as a limited or impaired ability to perform movements. Most studies have dealt with the effects of pain on the spinal cord reflexes, but in recent years, several lines of evidence suggest that the interaction between motor and pain systems in conditions of pain induced experimentally, rather than a simple spinal reflex, is a more complex process that involves also supraspinal brain areas. Although pain-motor interaction shows different features and time course depending on different pain variables, such as duration (tonic versus phasic pain), submodalities (deep versus superficial pain) and location (distal versus proximal pain), a common finding is that pain is able to inhibit the motor cortex. This motor cortex inhibition may act as a sort of motor 'decerebration' so as to allow the spinal motor system to freely develop protective responses to noxious stimulation. Further studies are required to assess the effects of pain on the motor system in patients suffering from chronic pain, in order to develop innovative rational therapeutic strategies to reduce both pain and motor disability.

The study aim was to evaluate the effect of different attentional tasks on the amplitudes and latencies of painful and non-painful contact heat evoked potentials (CHEPs). CHEPs were recorded in 12 healthy subjects during two experimental conditions, in which attention was oriented towards the intensity and the distress caused by the stimuli and were compared with CHEPs recorded during a neutral condition. The painful heat stimulation produced a negative potential at Cz vertex with a latency around 540 ms (Cz/N540), a positive peak at Cz electrode around 730 ms (Cz/P730) and, lastly, a positive peak around 1000 ms (Pz/P1000) in the Pz traces. The Cz/P730 wave was significantly higher in amplitude only during the painful stimulation and is probably related to coding the nociceptive activity. Varying the attentional target towards different properties of the stimulus did not cause any significant change in CHEP responses amplitude and latencies compared with the neutral condition. Our results suggest that CHEPs represent a reliable functional measure of the nociceptive pathways and that they are generated by the activation of different cerebral areas involved in pain processing. The high activation level of each of these area or their spatial neighbouring might explain the strong similarity of CHEP components recorded during different attentional manipulations.

Contact heat evoked potentials (CHEPs) were collected in 12 healthy subjects by stimulating the forearm skin with a couple of thermodes at a painful intensity. The stimulated area was 628 mm(2) and the repetition rate was 0.1 Hz. The electroencephalogram was recorded by 31 electrodes placed on the scalp according to an extended 10-20 System. A dipolar model explaining the scalp CHEP distribution was built by using the brain electrical source analysis. The model includes two dipoles located bilaterally in the perisylvian region, one dipole in the deep midline region and two dipoles located bilaterally in the deep temporal lobe. This dipolar model is very similar to that previously described to explain the topography of evoked potentials to radiant heat stimulation by laser pulses. Since laser stimuli activate the nociceptive fibres, the strong similarity of the cerebral dipoles activated by contact heat stimuli and by laser pulses suggests that only nociceptive inputs are involved in the scalp painful CHEP building. Therefore, CHEP recording can be useful for clinical examination of the nociceptive system.

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. [ABSTRACT FROM AUTHOR]

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]

Objective: To investigate the possible contribution of the primary somatosensory area (SI) to pain sensation.Methods: Depth recordings of CO2 laser evoked potentials (LEPs) and somatosensory evoked potentials (SEPs) were performed in an epileptic patient with a stereotactically implanted electrode (Talairach coordinates y=−23, z=40) that passed about 10 mm below the hand representation in her left SI area, as assessed by the source of the N20 SEP component.Results: The intracerebral electrode was able to record the N20 SEP component after non-painful electrical stimulation of her right median nerve. The N20 potential showed a phase reversal in the bipolar montage (at about 31 mm from the midline), which confirms that the electrode was located near its generator in area 3b. In contrast, no reliable response was recorded from the SI electrode after painful CO2 laser stimulation of the right hand. An N2-P2 response was evoked at the vertex electrode (Cz), thus demonstrating the effectiveness of the delivered CO2 laser stimuli.Conclusions: Since the N20 SEP component originates from the anterior bank of the post-central gyrus (area 3b), our result suggests that this part of SI does not participate in LEP generation. In fact, the previously published LEP sources in the SI area estimated from scalp recordings are about 10–17 mm posterior of the electrode in our patient, suggesting that they are more likely located in area 1, 2 or posterior parietal cortex. [Copyright &y& Elsevier]

Abstract: 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 CO2 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, CO2 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. [Copyright &y& Elsevier]