Laser-evoked Potentials Amplitude Research Articles

Somatosensory function is impaired in patients with idiopathic REM sleep behaviour disorder

BackgroundIdiopathic REM sleep behaviour disorder (iRBD) has been recognised as a significant biomarker for developing a neurodegenerative alpha-synucleinopathy, which is why iRBD is considered to be a prodromal state for alpha-synucleinopathies including Parkinson's disease (PD). Many patients with PD suffer from complaints of pain and present impaired somatosensory function. We hypothesized that pain perception and somatosensory function could be altered already in a preclinical stage of PD including iRBD. Hence, the objective of this study was to investigate pain perception and somatosensory function in patients with iRBD. MethodsQuantitative sensory testing (QST), laser evoked potentials (LEPs), and conditioned pain modulation (CPM) testing were performed in 13 iRBD patients without any clinical signs of PD or narcolepsy (11 males, 2 females, mean age 65.2 years) and 15 gender- and age-matched healthy control subjects (12 males, 3 females, mean age 65.8 years). ResultsThermal detection thresholds were higher in the iRBD group compared with the control group (cold detection threshold (CDT) p = 0.020, thermal sensory limen (TSL) p = 0.001), indicating an impaired temperature sensation in iRBD patients. The N2/P2 LEPs amplitude was smaller in iRBD patients than controls, but not statistically significant (p = 0.053). ConclusionsThis study found an impaired somatosensory function in iRBD patients, suggesting that somatosensory impairment might be an early feature in the neurodegenerative process of PD.

Habituation of laser-evoked potentials by migraine phase: a blinded longitudinal study

BackgroundMigraineurs seem to have cyclic variations in cortical excitability in several neurophysiological modalities. Laser-evoked potentials (LEP) are of particular interest in migraine because LEP specifically targets pain pathways, and studies have reported different LEP-changes both between and during headaches. Our primary aim was to explore potential cyclic variations in LEP amplitude and habituation in more detail with a blinded longitudinal study design.MethodsWe compared N1 and N2P2 amplitudes and habituation between two blocks of laser stimulations to the dorsal hand, obtained from 49 migraineurs with four sessions each. We used migraine diaries to categorize sessions as interictal (> one day from previous and to next attack), preictal (< one day before the attack), ictal or postictal (< one day after the attack). Also, we compared 29 interictal recordings from the first session to 30 controls.ResultsN1 and N2P2 amplitudes and habituation did not differ between preictal, interictal and postictal phase sessions, except for a post hoc contrast that showed deficient ictal habituation of N1. Habituation is present and similar in migraineurs in the interictal phase and controls.ConclusionsHand-evoked LEP amplitudes and habituation were mainly invariable between migraine phases, but this matter needs further study. Because hand-evoked LEP-habituation was similar in migraineurs and controls, the present findings contradict several previous LEP studies. Pain-evoked cerebral responses are normal and show normal habituation in migraine.

Pain Processing and Vegetative Dysfunction in Fibromyalgia: A Study by Sympathetic Skin Response and Laser Evoked Potentials.

Background A dysfunction of pain processing at central and peripheral levels was reported in fibromyalgia (FM). We aimed to correlate laser evoked potentials (LEPs), Sympathetic Skin Response (SSR), and clinical features in FM patients. Methods Fifty FM patients and 30 age-matched controls underwent LEPs and SSR by the right hand and foot. The clinical evaluation included FM disability (FIQ) and severity scores (WPI), anxiety (SAS) and depression (SDS) scales, and questionnaires for neuropathic pain (DN4). Results The LEP P2 latency and amplitude and the SSR latency were increased in FM group. This latter feature was more evident in anxious patients. The LEPs habituation was reduced in FM patients and correlated to pain severity scores. In a significant number of patients (32%) with higher DN4 and FIQ scores, SSR or LEP responses were absent. Conclusions LEPs and SSR might contribute to clarifying the peripheral and central nervous system involvement in FM patients.

P246 Abdominal acupuncture reduces pain at the spinal cord level

Objective Abdominal acupuncture (AA) reduces laser-evoked potentials (LEP) amplitude and laser pain perception in healthy subjects (Pazzaglia et al., 2014). The aim of the current study was to investigate the site of AA analgesic effect. Methods We recorded LEPs in 10 healthy volunteers by using the 32 EEG scalp electrodes.The experimental protocol included 3 times: (1) baseline, in which LEPs to stimulation of the bilateral dorsal wrist and right foot were recorded before acupuncture; (2) acupuncture, in which LEPs were recorded during AA performed in the abdominal area corresponding to right wrist; (3) rest, in which LEPs were recorded 15 min after the needle removal. Results The N2/P2 LEP amplitude to stimulation of both wrist was reduced in the acupuncture and rest times as compared to baseline, while LEP amplitude to foot stimulation was not modified. Discussion Abdominal acupuncture is able to reduce LEP amplitude. Since the homotopic regions of both sides are possibly connected within the spinal cord, our results suggest that the AA analgesic effect occurs at spinal level. On the other hand, the absence of any modulation of LEPs to foot stimulation is against the possibility of an AA general inhibitory effect. Conclusion AA exerts an analgesic effect at the spinal cord level. Significance AA can be considered as a non-pharmacological analgesic treatment.

Efficacy of the topical 5% lidocaine medicated plaster in the treatment of chronic post-thoracotomy neuropathic pain.

To assess the efficacy of the topical 5% lidocaine medicated plaster (Versatis®, Grünenthal GmbH, Aachen, Germany) in patients with post-thoracotomy neuropathic pain. Patients were randomized to receive the topical 5% lidocaine medicated plaster (n = 33) or non-medicated placebo plasters (n = 30) for 12 h every day for 8 weeks. Laser-evoked potentials (LEPs) were measured, and various questionnaires/scales completed. Numeric Rating Scale pain scores improved significantly (p < 0.01) more in topical 5% lidocaine medicated plaster than in placebo recipients. The same was true for N2 and P2 LEP latency and amplitude, and other parameters. The study included neurophysiological findings and confirmed the efficacy of the topical 5% lidocaine medicated plaster in patients with chronic post-thoracotomy neuropathic pain.

5. Cerebellar direct current stimulation modulates pain perception and its neural correlates in humans

The cerebellum is involved in a number of integrative functions, but its role in pain perception and nociceptive processing is poorly understood. We evaluated the effects of transcranial cerebellar direct current stimulation (tcDCS) by studying changes in perceptive threshold (PT), pain intensity (VAS) and laser evoked potentials (LEPs). Twenty-five subjects were studied before and after anodal, cathodal and sham tcDCS. LEPs were obtained using a Nd:YAP laser. VAS was evaluated by delivering laser pulses at two different intensities, respectively two and three times the PT. Cathodal polarization dampened the perceptive threshold and increased the VAS score, while anodal one had opposite effects (p < 0.001, two-way repeated measures ANOVA, “time” × “stimulation”). Cathodal tcDCS increased LEPs amplitudes and decreased their latencies, whereas anodal polarization elicited opposite effects (p < 0.0001). Motor thresholds assessed through transcranial magnetic stimulation were not affected by tcDCS. tcDCS modulates pain perception and its cortical correlates. As it is effective on N1 and N2/P2 components, we speculate that the cerebellum modulates the activity of both somatosensory and cingulate cortices, thus interfering with the sensory-discriminative and affective-emotional dimensions of pain. Our findings prompt investigation of the tsDCS as a novel and safe therapeutic tool in pain syndromes.

14. Abdominal acupuncture reduces pain at spinal level

Abdominal acupuncture (AA) reduces laser-evoked potentials (LEP) amplitude and laser pain perception in healthy subjects (Pazzaglia et al., 2014). The aim of the current study was to investigate the site of AA analgesic effect. We recorded LEPs in 6 healthy volunteers by using 32 EEG scalp electrodes. The experimental protocol included 3 times: (1) baseline, in which LEPs evoked to stimulation of the bilateral dorsal wrist and right foot were recorded before acupuncture; (2) acupuncture, in which LEPs were recorded during AA performed in the abdominal area corresponding to right wrist; (3) rest, in which LEPs were recorded 15 min after the needle removal. Compared to baseline, N2/P2 LEP amplitude evoked by stimulation of both wrists was reduced in the acupuncture and rest times while LEP amplitude evoked by foot stimulation was not modified. Our results suggest that the AA analgesic effect occurs at spinal level.

Distinct Somatic Discrimination Reflected by Laser-Evoked Potentials Using Scalp EEG Leads.

Discrimination is an important function in pain processing of the somatic cortex. The involvement of the somatic cortex has been studied using equivalent dipole analysis and neuroimaging, but the results are inconsistent. Scalp electroencephalography (EEG) can reflect functional changes of particular brain regions underneath a lead. However, the responses of EEG leads close to the somatic cortex in response to pain have not been systematically evaluated. The present study applied CO2 laser stimulation to the dorsum of the left hand. Laser-evoked potentials (LEPs) of C4, T3, and T4 leads and pain ratings in response to four stimulus intensities were analyzed. LEPs started earlier at the C4 and T4 leads. The onset latency and peak latency of LEPs for C4 and T4 leads were the same. Only 10 of 22 subjects (45 %) presented equivalent current dipoles within the primary somatosensory or motor cortices. LEP amplitudes of these leads increased as stimulation intensity increased. The stimulus–response pattern of the C4 lead was highly correlated with pain rating. In contrast, an S-shaped stimulus–response curve was obtained for the T3 and T4 leads. The present study provides supporting evidence that particular scalp channels are able to reflect the functional characteristics of their underlying cortical areas. Our data strengthen the clinical application of somatic-cortex-related leads for pain discrimination.

Differences in Pain Perception Between Men and Women of Reproductive Age: A Laser-Evoked Potentials Study.

We investigated differences in pain perception between men and women of reproductive age by using Laser-Evoked Potentials (LEPs). Forty-four right-handed healthy volunteers (19 males/25 females), aged 30–40 years were studied. A CO2 laser generated three series of 10 thermal pulses (4.5 W) on the radial aspect of the dorsum of the left hand. A recording montage for late LEPs was used, and the potentials of each series of stimuli were averaged to calculate mean latency and amplitude for each subject. Volunteers scored verbally pain intensity (Numerical rating scale [NRS]; 0–10). Three series of 10 numbers were averaged for calculation of mean NRS score. LEP peak-to-peak amplitude, latency, and NRS scoring were compared between genders, and correlations between LEP amplitude/latency and NRS scores were assessed. Data from 44 subjects were analyzed. LEP amplitudes differed significantly (P < 0.001) between men (24.2 ± 6.0 µV) and women (38.9 ± 15.28 µV), while no difference was found for latency (156.5 ± 8.6 versus 160.4 ± 19.8 ms, P = 0.42) or NRS score (2.6 ± 1.5 versus 2.4 ± 1.4, P = 0.63), respectively. Menstrual cycle phase did not influence LEP parameters (P = 0.59 for amplitude and P = 0.69 for latency) or NRS score (P = 0.95). No significant correlation was found between latency or amplitude and NRS score (P = 0.43 and P = 0.90, respectively). Our results demonstrate a significant gender-related difference in LEP amplitudes with lower mean values in men, while no difference was found in LEP latencies or in subjective pain ratings. Further research is required to clarify the clinical significance of the above experimental findings.

Expectation to feel more pain disrupts the habituation of laser-pain rating and laser-evoked potential amplitudes

Increased pain perception due to the expectation to feel more pain is called nocebo effect. The present study aimed at investigating whether: (1) the mere expectation to feel more pain after the administration of an inert drug can affect the laser-pain rating and the laser-evoked potential (LEP) amplitude, and (2) the learning potentiates the nocebo effect. Eighteen healthy volunteers were told that an inert cream, applied on the right hand, would increase the laser pain and LEP amplitude to right hand stimulation. They were randomly assigned to either “verbal session” or “conditioning session”. In the “verbal session”, LEPs to both right and left hand stimulation were recorded at the same intensity before (baseline) and after cream application. In the “conditioning session”, after an initial cream application the laser stimulus intensity was increased surreptitiously to make the subjects believe that the treatment really increased the pain sensation. Then, the cream was reapplied, and LEPs were recorded at the same stimulus intensity as at the baseline. It was found that the verbal suggestion to feel more pain disrupted the physiological habituation of the laser-pain rating and LEP amplitude to treated (right) hand stimulation. Unlike previously demonstrated for the placebo effect, the learning did not potentiate the nocebo effect.

17. Pain modulation in patients with Multiple Sclerosis, pain and spasticity after oromucosal cannabinoid spray (THC/CBD): A study with quantitative sensory testing and laser evoked potentials

Oromucosal cannabinoid (THC/CBD) spray administration for the treatment of pain in patients affected by Multiple Sclerosis (MS) has been well documented and MS patients generally complain of different kind of pain, including spasticity-related and neuropathic pain. Our purpose was to examine pain modulation and thermal/pain threshold of MS patients before and after THC/CBD. 16 MS patients underwent clinical examination (including NRS scale), Quantitative Sensory Testing (QST) and Laser Evoked Potentials (LEPs) before and after one month of oromucosal spray. Psychophysiological and neurophysiological testing were compared to sex- and age-matched controls. Patients reported a significant reduction in pain (NRS 7,2 /4,7 before/after THC/CBD); QST thresholds were altered in patients and did not change after THC/CBD; there was a significant reduction of LEPs amplitude and increase of LEPs latency in MS patients compared to controls and no significant threshold or LEPs parameters change was noted after drug administration. Our results suggest that THC/CBD is effective on pain but LEPs and QST are not sensitive enough to detect pain modulation; the fact may be dependent on different factors, including the high disease burden as well as different kind of pains (nociceptive and neuropathic) affecting MS patients.

Can “pain matrix” be convinced to feel more pain? Looking for a neurophysiological marker of nocebo effect

Objectives To investigate whether the expectation of feeling more pain modifies laser evoked potential (LEP) amplitude and laser-pain rating. Methods Twenty subjects were recruited: 10 in a verbal suggestion session (VSS) and 10 in a conditioning session (CS). At time 0, LEPs were acquired from 31 scalp electrodes to right and left hand stimulation. At time 1, Vaseline was applied on the right hand and subjects were informed that they were receiving a hyperalgesic cream. In VSS, LEPs were recorded using the same stimulus intensity as in the baseline. In CS, LEPs were recorded initially to a stimulus of surreptitiously increased intensity, in order to make the subjects believe that the treatment worked. Then, Vaseline was applied again and LEPs were recorded at the same stimulus intensity as in the baseline. Results In VSS, laser-pain rating was increased after treatment. In both VSS and CS, the fake treatment did not produce any increase of both N2 and P2 amplitudes. No topographical modification was observed. Conclusions The expectation of feeling more pain increases the laser-pain rating, but not the LEP amplitude. Key message The subjective evaluation of pain is integrated in a more complex brain network than that generating LEPs.

High Hypnotizability Impairs the Cerebellar Control of Pain

In the general population, transcranial anodal direct current stimulation of the cerebellum (ctDCS) reduces pain intensity and the amplitude of nociceptive laser evoked potentials (LEPs), whereas cathodal ctDCS elicits opposite effects. Since behavioral findings suggest that the cerebellar activity of highly hypnotizable individuals (highs) differs from the general population, we investigated whether hypnotizability-related differences occur in the modulation of pain by ctDCS. Sixteen healthy highs (according to the Stanford Hypnotic Susceptibility Scale, form A) and 16 participants not selected according to hypnotizability (controls) volunteered to undergo laser nociceptive stimulation of the dorsum of the left hand before and after anodal or cathodal ctDCS. LEPs amplitudes and latencies and the subjective pain experience (Numerical Rating Scale) were analyzed. Smaller LEP amplitudes and longer latencies were observed in highs with respect to controls independently of stimulation. After anodal and cathodal cerebellar stimulation, controls reported lower and higher pain than before it, respectively. In contrast, highs did not report significant changes in the perceived pain after both stimulations. They increased significantly their N2/P2 amplitude after anodal ctDCS and did not exhibit any significant change after cathodal tDCS, whereas controls decreased the N1 and N2P2 amplitude and increased their latency after anodal cerebellar stimulation and did the opposite after cathodal ctDCS. In conclusion, the study showed impaired cerebellar pain modulation and suggested altered cerebral cortical representation of pain in subjects with high hypnotizability scores.

Peripheral sensitization reduces laser-evoked potential habituation

Laser-evoked potential (LEP) habituation was investigated under the influence of capsaicin-induced peripheral and central sensitization. Fifteen subjects received 100 repetitive painful laser stimuli at the right hand dorsum at primary (application area; condition I) and secondary areas (beyond application area; condition II) in two different sessions after applying capsaicin topically. Conditions I and II were compared to a control condition without capsaicin application. N1, N2, and P2 latencies and N1 and N2/P2 amplitudes were recorded by EEG. Quantitative sensory testing (QST) and the Liewald Diary reaction time experiment were used as control tests. QST documented heat hyperalgesia as a sign of peripheral sensitization in the primary area and pinprick hyperalgesia in the primary and secondary area as a sign of central sensitization, after applying capsaicin. The N2/P2 amplitude habituation was significantly reduced in the primary area compared to controls (the primary area represents peripheral sensitization). The LEPs of the secondary area (the secondary area represents central sensitization) showed no significant N2/P2 amplitude habituation compared to controls. The comparison between conditions I vs. II showed no significant difference regarding N2/P2 amplitude and laser pain rating. Capsaicin-induced central sensitization does not alter LEP habituation. The physiological habituation of LEP amplitudes is reduced due to peripheral mechanisms after applying capsaicin topically. These findings form a basis for future studies, which use the habituation paradigm to investigate pain conditions promoted by sensitization phenomena.

Laser-evoked potentials mediated by mechano-insensitive nociceptors in human skin.

Laser-evoked potentials (LEP) were assessed after peripheral nerve block of the lateral femoral cutaneous nerve (LFCN) in healthy volunteers from partially anesthetized skin areas to differentially stimulate mechano-insensitive nociceptors. An ultrasound-guided nerve block of the LFCN was performed in 12 healthy male subjects with Ropivacain 1%. After 30min, the nerve block induced significantly larger anesthetic areas to mechanical stimuli than to electrical stimuli revealing an area of differential sensitivity. LEPs, reaction times and pain ratings were recorded in response to the laser stimuli of (1) completely anesthetic skin, (2) mechano-insensitive, but electrically excitable skin ('differential sensitivity'), (3) normal skin. LEP latencies in the area of differential sensitivity were increased compared to unaffected skin (228±8.5ms, vs. 181±3.6ms, p<0.01) and LEP amplitudes were reduced (14.8±1.2μV vs. 24.6±1.7μV, p<0.01). Correspondingly, psychophysically assessed response latencies in the differentially anesthetic skin were increased (649ms vs. 427ms, p<0.01) and pain ratings reduced (1.5/10 vs. 5/10 NRS, p<0.01). The increase in LEP latency suggests that mechano-insensitive heat-sensitive Aδ nociceptors (MIA, type II) have a slower conduction velocity or higher utilization time than mechano-sensitive type II Aδ nociceptors. Moreover, widely branched, slowly conducting and mechano-insensitive branches of Aδ nociceptors can explain our finding. LEPs in the differentially anesthetized skin provide specific information about a mechanically insensitive but heat-sensitive subpopulation of Aδ nociceptors. These findings support the concept thatA-fibre nociceptors exhibit a similar degree of modality specificity as C-fibre nociceptors.

P042. Mechanism of action and clinical evidence of botulinum toxin in chronic migraine.

Considerable evidence exists supporting the notion that botulinum toxin type A (BoNT/A) can exert a direct analgesic effect in addition to its myorelaxant effect. It is likely that the benefict of using BoNT/A as prophylactic treatment for chronic migraine is due to its ability to inhibit overactivity of motor neurons and hyperexcitability of sensory neurons, by involving the suppression of peripheral and central sensitization. In this study we aimed to evaluate the effects of BoNT/A on amplitude, latency and habituation of laser evoked potentials (LEPs) in patients with chronic migraine. We recruited 20 patients with a diagnosis of chronic migraine treated with type A botulinum toxin every 3 months. LEPs were recorded in basal, two hours and ten days after both BoNT/A and placebo injection. Headache frequency, allodynia and total tenderness score (TTS) were evaluated at basal condition and after one-year of treatment. We found N2 and P2 latency increased 10 days after toxin injection, while LEPs amplitude was not modified. Compared to placebo injection, the habituation of N2/P2 LEPs component obtained by stimulating supraorbital zone was significantly increased after BoNT/A infiltration. After ten days, habituation pattern in migraine patients was similar to that of normal subjects. In the one-year follow-up we observed a significant migraine frequency and allodynia improvement, but no effect on total tenderness score. Furthermore the habituation change correlated with the clinical effectiveness. Study results suggest a toxin modulating action on nociceptive afferents in patients with chronic migraine. The N2 and P2 latency increase obtained from hand laser stimulation suggests a possible systemic pain inhibiting effect. Although the botulinum toxin did not show an inhibitory effect on trigeminal nociceptive system, it seems to improve the reduced habituation pattern which promotes the central sensitization. The therapeutic effect of BoTN/A seemed to be related to the effect on trigeminal habituation obtained after 10 days from the first infiltration, which could be considered as a potential neurophysiological pattern to predict the non-responders. Results of this study confirm that the effect of botulinum toxin on chronic migraine may be related to a modulation and normalization of central sensitization mechanisms. The lack of effects on pericranial muscle tension precludes to suppose a modulating effect on trigeminal nociception by the inhibition of the neuromuscular synapse. Written informed consent to publish was obtained from the patient(s).

Characterization of Pain in Familial Amyloid Polyneuropathy

Familial amyloid polyneuropathy (FAP) caused by transthyretin (TTR) mutation is a small-fiber predominant polyneuropathy, exposing patients with TTR-FAP to development of neuropathic pain. However, the painful nature of TTR-FAP has never been specifically addressed. In this study, we compared 2 groups of 16 patients with either painless or painful TTR-FAP with regard to various clinical and neurophysiologic variables, including laser evoked potential (LEP) recording and quantitative sensory testing. The 2 groups of patients did not differ on any clinical or neurophysiologic variable. Patients with painful TTR-FAP complained of ongoing burning pain sensations, pain aggravation at rest, paroxysmal pain (electric shock and stabbing sensations), or provoked pain (mostly dynamic mechanical allodynia). However, the symptomatic presentation of painful TTR-FAP evolved with the course of the disease. The duration of the disease and the severity of small-fiber lesions (increase in thermal thresholds and reduction in LEP amplitude) correlated negatively with the intensity of ongoing burning sensations and positively with the intensity of paroxysmal pain. In addition, small-fiber preservation correlated positively with cold allodynia and pain aggravation at rest and negatively with dynamic mechanical allodynia. Peripheral sensitization of small-diameter nociceptive axons might occur in early TTR-FAP and be responsible for the burning sensation and cold allodynia. As polyneuropathy and small-fiber loss progress, paroxysmal pain and dynamic mechanical allodynia may develop as a result of central sensitization generated by abnormal activities affecting relatively spared large-diameter sensory fibers. PerspectivePain in TTR-FAP includes several mechanisms varying with the course of the disease and the involvement of the different types of nerve fibers.

Laser-Evoked Vertex Potentials Predict Defensive Motor Actions.

The vertex potential is the largest response that can be recorded in the electroencephalogram of an awake, healthy human. It is elicited by sudden and intense stimuli, and is composed by a negative–positive deflection. The stimulus properties that determine the vertex potential amplitude have been well characterized. Nonetheless, its functional significance remains elusive. The dominant interpretation is that it reflects neural activities related to the detection of salient stimuli. However, given that threatening stimuli elicit both vertex potentials and defensive movements, we hypothesized that the vertex potential is related to the execution of defensive actions. Here, we directly compared the salience and motoric interpretations by investigating the relationship between the amplitude of laser-evoked potentials (LEPs) and the response time of movements with different defensive values. First, we show that a larger LEP negative wave (N2 wave) predicts faster motor response times. Second, this prediction is significantly stronger when the motor response is defensive in nature. Third, the relation between the N2 wave and motor response time depends not only on the kinematic form of the movement, but also on whether that kinematic form serves as a functional defense of the body. Therefore, the N2 wave of the LEP encodes key defensive reactions to threats.

Central habituation and distraction alter C‐fibre‐mediated laser‐evoked potential amplitudes

Recent studies applied laser-evoked potentials (LEP) for the analysis of small nerve fibre function and focused on the detection of stable C-fibre-mediated potentials (C-LEPs); high technical requirements were needed. The diagnostic significance is still controversially discussed. So far, only few studies focused on the susceptibility of C-LEPs to distraction and other influences. We hypothesized that C-LEPs are altered by habituation processes and distraction. Twelve subjects were tested with a C-fibre laser set-up (neodymium:yttrium-aluminium-perovskite laser with a 10-mm beam diameter and 10-ms stimulus time) at the left perioral area. In condition I, the subjects received repetitive painful laser stimuli at the right hand to induce habituation. In condition II, the subjects had to fulfil an auditory discrimination task (where the subjects had to estimate the pitch of different tones on a scale for 20min). C-LEPs were retrieved before and after the habituation or distraction paradigm. C-LEPs were also measured in a control group who was not influenced by laser stimuli or other disturbances during a 23-min break between the two test sessions. In both test conditions, there was significant C-LEP amplitude reduction. The LEP amplitudes of the control group remained unchanged. In the approach of detecting C-fibre-mediated potentials with LEP, future studies should take the high susceptibility to distraction and habituation into account.

Effect of sleep deprivation on the electrophysiological signature of habituation to noxious laser stimuli.

Sleep deprivation induces hyperalgesia. However, this pro-nociceptive effect is not reflected at the electrophysiological level, since sleep restricted subjects show amplitude reduction of Laser-evoked Potentials (LEP). We aimed to explore the contribution of habituation to this paradoxical LEP amplitude decline. We compared LEP's of 12 healthy students (23.2 ± 1.1 years) after habitual sleep (HS) and a night of total sleep deprivation (TSD). Twelve repetitive laser stimulus blocks (each comprising twenty stimuli) were applied under three attention conditions ('focusing' - 'neutral' - 'distraction' condition). Stimulus blocks were split in part 1 (stimulus 1-10) and part 2 (stimulus 11-20). The contribution of habituation to the TSD-induced LEP amplitude decline was studied by calculating the percentage amplitude reduction of part 2 as compared to part 1. Individual sleepiness levels were correlated with (1) averaged LEP's and (2) the degree of habituation. TSD induced hyperalgesia to laser stimuli (p < 0.001). In contrast, depending on the attention condition, the P2 amplitude of the N2P2-complex was significantly reduced ('focusing': p = 0.004; 'neutral': p = 0.017; distraction: p = 0.71). Habituation of the P2 amplitude to radiant heat was increased after TSD ('focusing': p = 0.04; 'neutral': p < 0.001; distraction: p = 0.88). TSD had no significant effect on N1 amplitudes (p > 0.05). Individual sleepiness correlated negatively with averaged P2 amplitudes (p = 0.02), but not with the degree of habituation (p = 0.14). TSD induces hyperalgesia and results in attention-dependent enhanced habituation of the P2 component. Increased habituation may--to a substantial degree--explain the TSD-induced LEP-amplitude decline. For this article, a commentary is available at the Wiley Online Library.