Laser-evoked Potentials Amplitude Research Articles

Motor cortex rTMS reduces acute pain provoked by laser stimulation in patients with chronic neuropathic pain

To assess the modulation of acute provoked pain by repetitive transcranial magnetic stimulation (rTMS) of the motor cortex in patients with chronic neuropathic pain. In 32 patients with chronic neuropathic pain affecting one upper limb, laser-evoked potentials (LEPs) (N2 and P2 components) were recorded in response to laser stimulation of the painful or painless hand, before and after active or sham rTMS applied at 10Hz over the motor cortex corresponding to the painful hand. Laser-induced pain was scored on a visual analogue scale. Both active and sham rTMS reduced N2-P2 amplitude of the LEPs in response to painful or painless hand stimulation, likely due to the decline of attention during the sessions. However, active rTMS, but not sham rTMS, specifically reduced N2 amplitude and N2/P2 amplitude ratio of the painful hand LEPs. Painful hand LEP attenuation correlated with the magnitude of pain relief produced by active rTMS. Motor cortex rTMS delivered at high frequency (10Hz) was able to reduce LEP amplitude in parallel with laser-induced pain scores in patients with chronic neuropathic pain. The preferential change in the N2 component suggested a modulation of the sensori-discriminative aspect of laser-induced pain. Previous studies have shown that rTMS delivered to various cortical targets by different protocols could modulate experimental pain, primarily in healthy subjects. The present results demonstrate the ability of motor cortex rTMS to interfere with the processing of acute provoked pain, even if there is an underlying chronic neuropathic pain.

Pain perception and laser evoked potentials during menstrual cycle in migraine

The association between estrogens “withdrawal” and attacks of migraine without aura is well-known. The aim of the study was to examine the features of laser evoked potentials (LEPs), including habituation, in women suffering from migraine without aura versus healthy controls, during the pre-menstrual and late luteal phases. Nine migraine without aura and 10 non-migraine healthy women, were evaluated during the pre-menstrual phase and late luteal phase. The LEPs were recorded during the inter-critical phase. The right supraorbital zone and the dorsum of the right hand were stimulated. Three consecutive series of 20 laser stimuli were obtained for each stimulation site. Laser pain perception was rated by a 0–100 VAS after each stimulation series. Migraine patients exhibited increased LEPs amplitude and reduced habituation compared to normal subjects. Laser-pain perception was increased during the pre-menstrual phase in both patients and controls. Migraine patients and controls showed increased P2 and N2–P2 amplitude in the pre-menstrual phase, on both stimulation sites. During the pre-menstrual phase the N2–P2 habituation appeared to be reduced in both migraine and healthy women. The estrogen withdrawal occurring during the menstrual cycle may favor reduced habituation of nociceptive cortex, which may facilitate pain symptoms and migraine in predisposed women.

Electrophysiological correlates of reduced pain perception after theta-burst stimulation

In an earlier study, we reported the antinociceptive effects of a special repetitive transcranial magnetic stimulation paradigm: continuous theta-burst stimulation (cTBS), when applied to human motor cortex. Here, we investigated whether the reduced subjective pain perception of 10 healthy individuals could be measured by changes in laser-evoked potentials, a reflection of pain related activations in the operculoinsular and midcingulate cortex. To minimize the effect of habituation during repeated laser stimulation, a bioadaptive design was used. However, both pain ratings and laser-evoked potential amplitudes were reduced after real and sham cTBS. When compared with sham stimulation, cTBS resulted in a significantly greater diminution of pain ratings and N2-P2 amplitudes on the hand contralateral to the site of motor cortex stimulation.

Differential involvement of A-delta and A-beta fibres in neuropathic pain related to carpal tunnel syndrome

Carpal tunnel syndrome (CTS), a common entrapment neuropathy involving the median nerve at the wrist, frequently manifests with neuropathic pain. We sought information on pain mechanisms in CTS.We studied 70 patients with a diagnosis of CTS (117 CTS hands). We used the DN4 questionnaire to select patients with neuropathic pain, and the Neuropathic Pain Symptom Inventory (NPSI) to assess the intensity of the various qualities of neuropathic pain. All patients underwent a standard nerve conduction study (NCS) to assess the function of non-nociceptive Aβ-fibres, and the cutaneous silent period (CSP) after stimulation of the IIIrd and Vth digits, to assess the function of nociceptive Aδ-fibres. In 40 patients (75 CTS hands) we also recorded laser-evoked potentials (LEPs) in response to stimuli delivered to the median nerve territory and mediated by nociceptive Aδ-fibres. We sought possible correlations between neurophysiological data and the various qualities of neuropathic pain as assessed by the NPSI.We found that the median nerve sensory conduction velocity correlated with paroxysmal pain and abnormal sensations, whereas LEP amplitude correlated with spontaneous constant pain.Our findings suggest that whereas paroxysmal pain and abnormal sensations reflect demyelination of non-nociceptive Aβ-fibres, spontaneous constant pain arises from damage to nociceptive Aδ-fibres.

Laser-evoked potentials as a tool for assessing the efficacy of antinociceptive drugs

Laser-evoked potentials (LEPs) are brain responses to laser radiant heat pulses and reflect the activation of Aδ nociceptors. LEPs are to date the reference standard technique for studying nociceptive pathway function in patients with neuropathic pain. To find out whether LEPs also provide a useful neurophysiological tool for assessing antinociceptive drug efficacy, in this double-blind placebo-controlled study we measured changes induced by the analgesic tramadol on LEPs in 12 healthy subjects. We found that tramadol decreased the amplitude of LEPs, whereas placebo left LEPs unchanged. The opioid antagonist naloxone partially reversed the tramadol-induced LEP amplitude decrease. We conclude that LEPs may be reliably used in clinical practice and research for assessing the efficacy of antinociceptive drugs.

Inhibition of Cortical Laser-Evoked Potentials by Transcutaneous Electrical Nerve Stimulation

Objectives. This study attempts to confirm the hypothesis that transcutaneous electrical stimulation (TENS) of peripheral Aβ fibers inhibits nociceptive processing, by quantifying the change of laser-evoked potential (LEP) components, using a 980-nm diode laser. Materials and Methods. Cutaneous heat stimuli were delivered to the dorsum of the right hand in 13 volunteers. LEPs and pain intensity ratings were recorded before, during, and after the use of TENS (110Hz) at the dorsolateral forearm. Area under the curve (AUC), LEP amplitudes (N2P2), and peak latencies (N2, P2) were calculated. The paired samples t-test was used for statistical analysis. Results. A significant reduction of LEP amplitudes and AUC was found during and after the use of TENS (p<0.05). After 10min of TENS this was associated with a clinically relevant decrease of pain intensity. Conclusions. Our data suggest that TENS inhibits nociceptive processing. Ten minutes of TENS exerts a clinically relevant pain reduction.

Dissociation between cutaneous silent period and laser evoked potentials in assessing neuropathic pain

In this study we investigate whether the cutaneous silent period (CSP)-an inhibitory response evoked in hand muscles by painful digital nerve stimulation-is useful for assessing nociceptive pathway function in patients with neuropathic pain. In 40 patients with peripheral neuropathy (21 without and 19 with neuropathic pain) we recorded the CSP in the abductor digiti minimi after fifth digit stimulation and also recorded laser evoked potentials (LEPs) after stimulation applied to the ulnar territory of the hand. Although the LEP amplitude was significantly lower in patients with pain than in those without (P < 0.005), the CSP duration did not differ between groups (P > 0.50). Pain intensity correlated significantly with LEP amplitudes (P < 0.005) but not with CSP duration (P > 0.5). Our findings indicate that the CSP is not useful for assessing nociceptive pathway function in patients with neuropathic pain.

Laser-evoked potentials in primary headaches and cranial neuralgias

Using neurophysiological methods to explore nociceptive pathways may improve knowledge of the functional changes subtending pain processing in the different forms of headache and facial pain. Laser-evoked potentials (LEPs) are a reliable neurophysiological assay for the clinical assessment of pain syndromes. Reduced amplitude of LEPs seems to characterize trigeminal neuralgia and painful temporomandibular disorders, suggesting the neuropathic origin of pain. In tension-type headache, as well as in fibromyalgia, enhanced pericranial LEP amplitude suggests the psychogenic origin of pain. In migraine, a normal amplitude of basal LEPs with reduced habituation and altered attentive modulation seems to express a general dysfunction of cortical pain processing, which may also contribute, other than to predispose, to the persistence of migraine. LEPs may be employed in the clinical evaluation of the neurophysiological and psychophysiological aspects of pain in the different forms of headaches and facial pain to improve the therapeutic approach and provide an objective measure of treatment efficacy.

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 CO 2 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 μV, 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.

Pergolide Increases the Efficacy of Cathodal Direct Current Stimulation to Reduce the Amplitude of Laser-Evoked Potentials in Humans

Transcranial direct current stimulation (tDCS) was recently reintroduced as a tool for inducing relatively long-lasting changes in cortical excitability in focal brain regions. Anodal stimulation over the primary motor cortex enhances cortical excitability, whereas cathodal stimulation decreases it. Prior studies have shown that enhancement of D2 receptor activity by pergolide consolidates tDCS-generated excitability diminution for up to 24 hours and that cathodal stimulation of the primary motor cortex diminishes experimentally induced pain sensation and reduces the N2–P2 amplitude of laser-evoked potentials immediately poststimulation. In the present study, we investigated the effect of pergolide and cathodal tDCS over the primary motor cortex on laser-evoked potentials and acute pain perception induced with a Tm:YAG laser in a double-blind, randomized, placebo-controlled, crossover study. The amplitude changes of laser-evoked potentials and subjective pain rating scores of 12 healthy subjects were analyzed prior to and following 15 minutes cathodal tDCS combined with pergolide or placebo intake at five different time points. Our results indicate that the amplitude of the N2 component was significantly reduced following cathodal tDCS for up to two hours. Additionally, pergolide prolonged the effect of the cathodal tDCS for up to 24 hours, and a significantly lowered pain sensation was observed for up to 40 minutes. Our study is a further step toward clinical application of cathodal tDCS over the primary motor cortex using pharmacological intervention to prolong the excitability-diminishing effect on pain perception for up to 24 hours poststimulation. Furthermore, it demonstrates the potential for repetitive daily stimulation therapy for pain patients.

Neurophysiologic study of central pain in patients with Parkinson disease

Patients with Parkinson disease (PD) may present with various types of pain. In some instances, no cause can be identified and pain is considered a primary disorder (primary central pain [PCP]). We hypothesized that PCP in patients with PD (PD-PCP) may be due to a dysfunction of pain pathways or the processing of pain inputs in the CNS. We carried out a psychophysical and neurophysiologic study in 9 patients with PD-PCP, 9 patients with PD without pain (PD-NoP), and 9 healthy control subjects. We assessed the clinical characteristics of pain, performed quantitative sensory testing with thermal probes, and recorded laser-evoked potentials (LEPs) and laser-induced sudomotor skin responses (1-SSRs) in "off" and "on" conditions. In "off" condition, patients with PD-PCP had lower heat pain and laser pinprick thresholds, higher LEP amplitudes, and less habituation of the l-SSR in comparison with PD-NoP patients and control subjects. Abnormalities were more marked in the most affected side. In "on" condition, psychophysical and neurophysiologic differences disappeared or were significantly attenuated. Conduction along peripheral and central pain pathways is normal in patients with Parkinson disease with or without primary central pain. However, apart from signs of hyperalgesia, our patients exhibited lack of habituation of sympathetic sudomotor responses to repetitive pain stimuli, suggesting an abnormal control of the effects of pain inputs on autonomic centers. Abnormalities were attenuated by l-dopa, suggesting that the dysfunction may occur in dopamine-dependent centers regulating both autonomic function and inhibitory modulation of pain inputs.

Attenuation of N2 amplitude of laser-evoked potentials by theta burst stimulation of primary somatosensory cortex

Theta burst stimulation (TBS) is a special repetitive transcranial magnetic stimulation (rTMS) paradigm, where bursts of low-intensity stimuli are applied in the theta frequency. The aim of this study was to investigate the effect of neuronavigated TBS over primary somatosensory cortex (SI) on laser-evoked potentials (LEPs) and acute pain perception induced with Tm : YAG laser stimulation. The amplitude changes of the N1, N2, and P2 components of LEPs and related subjective pain rating scores of 12 healthy subjects were analyzed prior to and following continuous TBS (cTBS), intermittent TBS (iTBS), intermediate TBS (imTBS), and sham stimulation. Our results demonstrate that all active TBS paradigms significantly diminished the amplitude of the N2 component, when the hand contralateral to the site of TBS was laser-stimulated. Sham stimulation condition had no significant effect. The subjective pain perception also decreased during the experimental sessions, but did not differ significantly from the sham stimulation condition. The main finding of our study is that TBS over SI diminished the amplitude of the N2 component evoked from the contralateral side without any significant analgesic effects. Furthermore, imTBS produced responses similar to those observed by other forms of TBS induced excitability changes in the SI.

Analgesic and antinociceptive effects of peripheral nerve neurostimulation in an advanced human experimental model

Electrical peripheral nerve neurostimulation (PNS) is reported to be an effective pain treatment. An objective proof of antinociceptive effect is lacking. The human experimental study addressed PNS effects on nociception and pain by electrophysiology and psychophysics. In 23 healthy volunteers, 39 sessions were conducted. Three experiments (PNS ipsilateral, PNS contralateral, Control) consisted of 13 sessions each. Conditioning PNS (100 Hz) of left (PNS ipsilateral) or right (PNS contralateral) superficial radial nerve trunk evoked non-painful, tingling sensations on the hand dorsum. Local cutaneous anesthesia at PNS site provided for preferential nerve trunk stimulation. Cortical laser-evoked potentials (LEP) after painful stimulation at left hand dorsum were recorded together with mechanical and thermal perception thresholds at the same site before ( T1), during ( T2), and after ( T3) PNS or a no stimulation period (Control). Mechanical and thermal perception decreased in the anesthetized area. Late LEP amplitude decreased independently of PNS site. Exclusively under ipsilateral PNS, N2 latency increased and laser ratings decreased. Mechanical detection threshold transiently increased during ipsilateral PNS at hand dorsum. PNS induced strong reduction of mechanical perception due to peripheral collision of orthodromic (test stimulus) and antidromic (PNS) selective Aβ fiber excitation. Delay of N2 component and reduction of laser pain were specific to ipsilateral PNS. Divergent and common effects of ipsilateral and contralateral PNS suggest a combination of peripheral and central antinociceptive mechanisms. The study in man documents inhibition of nociception and pain by PNS and provides with an experimental model for future objectives in neuromodulation.

Inhibitory effect of voluntary movement preparation on cutaneous heat pain and laser‐evoked potentials

In our study, preparation of voluntary movement was used to physiologically activate the motor cortex areas and the effect of this activation on CO(2) laser-evoked potentials (LEPs) was explored. LEPs were recorded from 31 scalp electrodes in 10 healthy subjects after painful stimulation of the right C6-C7 skin dermatomes. LEP stimuli were delivered in the time interval between a visual warning stimulus followed after 1 s. by an imperative stimulus. The imperative stimulus triggered: (i) no task in the baseline condition (Pain); (ii) flexion-extension movements of the second finger of the right hand in the movement condition (Pain + Movement); (iii) cognitive task (mathematic computation) in the distraction condition (Pain + Cognition). The experimental conditions were also repeated during application of laser stimuli on the left C6-C7 skin dermatomes. Compared with the baseline condition (no task required), during preparation of right-hand voluntary movement there was a significant reduction in LEP amplitude and subjective pain rating after right- but not after left-hand stimulation, which suggests that the observed effect cannot be attributed to a nonspecific reduction in attention toward painful stimulus. During preparation of a cognitive task, LEP amplitude was reduced compared to baseline. Our results represent the first neurophysiological suggestion that physiological activation of the motor cortex, occurring during movement preparation, inhibits cortical pain processing by a centrifugal mechanism.

Involuntary orientation of attention to unattended deviant nociceptive stimuli is modulated by concomitant visual task difficulty. Evidence from laser evoked potentials

Objective Recent laser evoked potential (LEP) studies showed that unattended rare intensity-deviant nociceptive stimuli enhance the LEP vertex positivity P2 (‘P400 effect’). It was hypothesized to reflect an involuntary switch of attention to nociceptive events. If true the P400 effect (1) should be produced when attention is focused on a task in another sensory modality (primary task), and (2) should be modulated by the primary task difficulty. Methods Subjects had to count the number of visual symbols presented on a screen. In a difficult condition, symbols were digits 1–4 (interference between amount and meaning). In an easy condition, symbols were letters X (no interference). Nociceptive CO 2 laser stimuli were simultaneously delivered on the left hand. Occasional stronger deviant stimuli (16%) were presented at random. In additional sessions, the strong stimuli were presented alone in homogenous series (100%). Results LEP amplitude at about 400 ms was larger for rare deviant than for homogenous stimuli. Visual task difficulty decreased LEP amplitude at this latency. Deviant stimuli seemed also to interfere with performance in the visual task. Conclusions The results give evidence for considering the P400 effect as reflecting an involuntary attentional shift to nociceptive events. Significance The study provides electrophysiological evidences for an intrusive capacity of pain to attract attention and to decrease behavioural performance in concurrent processes. In turn, such an attentional shift is tampered if attention is very engaged in a concomitant task.

Habituation of single CO2 laser–evoked responses during interictal phase of migraine

A reduced habituation of averaged laser–evoked potential (LEP) amplitudes was previously found in migraine patients. The aim of the present study was to assess the habituation of single LEP responses and pain sensation during the interictal phase in migraine patients. Fourteen migraine patients were compared with ten control subjects. The pain stimulus was laser pulses, generated by CO2 laser, delivered to right supraorbital zone. Patients were evaluated during attack–free conditions. The LEP habituation was studied by measuring the changes of LEP amplitudes across and within three consecutive repetitions of 21 non–averaged trials. In migraine patients the N2–P2 wave amplitudes did not show a tendency toward habituation across and, above all, within the three repetitions. Anomalous behaviour of nociceptive cortex during the interictal phase of migraine may predispose patients to headache occurrence and persistence.

Capsaicin failed in suppressing cortical processing of CO 2 laser pain in migraine patients

The aim of this study was to compare the properties of the nociceptive system in eight migraine without aura patients in the pain-free phase with 10 healthy controls, by evaluating the topography and the source of the CO 2 laser-evoked potentials (LEPs) obtained by the right supraorbital skin, during and after capsaicin topical application. In healthy subjects the acute cutaneous pain induced by capsaicin reduced the amplitude of the vertex LEPs and induced a posterior shifting of the P2 wave dipolar source within the anterior cingulate cortex. These functional changes seemed significantly reduced in migraine patients, for a disturbed pattern of pain modulation at the cortical level, which may subtend the onset and persistence of migraine.

Laser-evoked potentials: normative values

Objective: Laser-evoked potentials (LEPs) currently represent the most reliable and widely agreed method of investigating the Aδ-fibre pathways. Many studies dealt with the usefulness of LEPs in peripheral and central nervous system diseases. We aimed at gaining normative values for LEP data. Methods: Using a CO 2 laser stimulator we recorded LEPs after face, hand, and foot stimulation in 100 normal subjects. We measured the perceptive threshold, latency and amplitude of the main vertex components, and their side-to-side differences. We also studied the correlations between LEP data and age and body height, as well as gender differences. Results: Laser perceptive threshold increased and LEP amplitude decreased from face to foot ( P<0.0001). The latency of hand and foot-LEPs correlated significantly with body height ( P<0.0001). The amplitude, though not the latency, correlated with age ( P<0.0001). LEP data did not significantly differ between genders ( P>0.1). Conclusions: This study provides normative values for the main LEP data and their absolute and side-to-side limits, highlighting the physiological differences related to, body height, age, gender and stimulation site. Significance: Our data may help to improve the clinical reliability of LEPs as a diagnostic tool.

Segmental inhibition of cutaneous heat sensation and of laser-evoked potentials by experimental muscle pain

The aim of the study was to evaluate the effect of tonic muscle pain evoked by injection of 5% hypertonic saline in the right brachioradialis muscle on the somatosensory sensation of laser-evoked heat pain and laser-evoked potentials. The heat pain pathways were studied in 9 healthy human subjects by recording the scalp potentials evoked by CO 2 laser stimuli delivered on four sites: the skin above the right brachioradialis muscle (ipsilateral local pain), the wrist area where muscle pain was referred in all subjects (ipsilateral referred pain), and two areas on the left arm symmetrical to both local and referred pain (contralateral local pain and contralateral referred pain). Laser-evoked potentials were obtained from 31 scalp electrodes before saline injection, during saline infusion (bolus injection with 0.3ml saline infused over 20 s, followed by a steady infusion rate of 30ml/h for the next 25 min), and 20 min after muscle pain had disappeared. While the early N1/P1 component (around 130 ms and 145 ms of latency after stimulation of the skin over the brachioradialis muscle and the wrist, respectively) was not affected by muscle pain, the amplitudes of the later vertex laser-evoked potentials (N2 latency of around 175 ms and 210 ms after stimulation of the skin over the brachioradialis muscle and the wrist, respectively; P2 latency of around 305 ms and 335 ms after stimulation of the skin over the brachioradialis muscle and the wrist, respectively) evoked from ipsilateral local pain, ipsilateral referred pain, and contralateral local pain sites were significantly decreased during muscle pain compared with the baseline recording, while they recovered after pain had disappeared. At the same stimulation sites, the rating of the laser-evoked pain sensation was reduced significantly during muscle pain as compared with the baseline and it recovered after pain had disappeared. On the contrary, muscle pain did not show any effect on both laser-evoked pain and laser-evoked potential amplitude when the contralateral referred pain site was stimulated. The muscle pain inhibitory effect on both heat pain sensation and laser-evoked potential amplitude is probably mediated by an ipsilateral and contralateral segmental mechanism which acts also on the referred pain area, while more general inhibitory mechanisms, such as a distraction effect or a diffuse noxious inhibitory control, are excluded by the absence of any effect of muscle pain on laser-evoked pain and laser-evoked potentials obtained from a remote site, such as the contralateral referred pain area. Since muscle pain induced by hypertonic saline injection is very similar to clinical pain, our results can be useful in understanding the pathophysiology of the somatosensory modifications which can be observed in patients with musculoskeletal pain syndromes.