Laser-evoked Potentials Amplitude Research Articles

Unravelling the role of unmyelinated nerve fibres in trigeminal neuralgia with concomitant continuous pain

ObjectiveIn this clinical and neurophysiological study, we aimed to test trigeminal nerve fibre function in patients with trigeminal neuralgia, with and without concomitant continuous pain. MethodsWe enrolled 65 patients with a definite diagnosis of primary trigeminal neuralgia. Patients were grouped according to whether they experienced purely paroxysmal pain (36) or also had concomitant continuous pain (29). All participants underwent trigeminal reflex testing to assess the function of large non-nociceptive myelinated fibres and laser-evoked potentials to assess the function of small myelinated Aδ and unmyelinated C fibres. Neurophysiological examiners were blinded to the affected side. ResultsThe only neurophysiological abnormality distinguishing the two groups of patients was the side asymmetry of C fibre-related laser-evoked potential amplitude (p = 0.005), which was higher in patients with concomitant continuous pain than in patients with purely paroxysmal pain (indicative of a reduced C fibre-related laser-evoked potential amplitude in the affected side of patients with concomitant continuous pain). ConclusionsOur clinical and neurophysiological study indicates that in patients with trigeminal neuralgia concomitant continuous pain is associated with unmyelinated C fibre damage as assessed with laser-evoked potentials. SignificanceOur findings suggest that concomitant continuous pain is related to unmyelinated C fibre loss, possibly triggering abnormal activity in denervated trigeminal second-order neurons.

Just Breathe: Improving LEP Outcomes through Long Interval Breathing

Background: Laser-evoked potentials (LEPs) constitute an objective clinical diagnostic method used to investigate the functioning of the nociceptor system, including signaling in thin peripheral nerve fibers: Aδ and C fibers. There is preliminary evidence that phase locking LEPs with the breathing cycle can improve the parameters used to evaluate LEPs. Methods: We tested a simple breathing protocol as a low-cost improvement to LEP testing of the hands. Twenty healthy participants all underwent three variants of LEP protocols: following a video-guided twelve-second breathing instruction, watching a nature video, or using the classic LEP method of focusing on the hand being stimulated. Results: The breath protocol produced significantly shorter latencies as compared with the nature or classic protocol. It was also the least prone to artifacts and was deemed most acceptable by the subjects. There was no difference between the protocols regarding LEP amplitudes. Conclusions: Using a breathing video can be a simple, low-cost improvement for LEP testing in research and clinical diagnostics.

OC18: Transspinal direct current stimulation for pain treatment. Objective proof of concept, initial clinical findings and BDNF polymorphism

Introduction Transspinal Direct Current Stimulation (tsDCS) has been reported to block pain signaling. To approach clinical usage, two studies were performed. In both, the effect of BDNF polymorphism (Val/Met) was investigated. Materials and methods Study I Nineteen healthy controls, the anode over the tenth thoracic vertebra, the cathode over the shoulder. tsDCS: 2.5 A for 20 minutes, double blinded cross over design. Laser Evoked Potentials (LEPs): Stimulation of the dorsum of the hand and foot respectively, recordings at baseline, immediately after- and 30 minutes after the tsDCS stimulation. Amplitude and latency of the N2 peak was assessed and the subjects rated pain intensity. BDNF polymorphism was investigated in DNA from buccal mucosa cells. Study II Patients with neuropathic pain due to polyneuropathy are recruited. tsDCS is given at three days with one day between, BDNF polymorphism investigated as above. Results Study I Group level: LEP amplitudes successively reduced over time. Placebo; latencies unaffected from upper-, slightly increased from lower extremities. Verum; transiently increased from upper-, accumulatively increased from lower extremities in proportion to experienced pain. Individual level: Large variations. BDNF polymorphism influences the effect of stimulation with less pain reduction in those with less active BDNF (Val/Val). Study II Fourteen patients have been investigated. The results will be presented at the conference. Conclusions Short term, anodal thoracic tsDCS affects transspinal pain signaling with large inter-individual differences. Individualized tsDCS may be a treatment option for neuropathic pain. The type of BDNF one carries, seem to influence the effect of stimulation.

Laser evoked potentials in fibromyalgia with peripheral small fiber involvement

ObjectiveTo evaluate multichannel laser evoked potentials (LEPs) in patients with fibromyalgia (FM) and small fiber impairment. MethodsWe recorded LEPs using 65 electrodes in 22 patients with FM and proximal denervation, 18 with normal skin biopsy, and 7 with proximal and distal intraepidermal nerve fiber density (IENFD) reduction. We considered the amplitude and topographical distribution of N1, N2 and P2 components, and habituation of N2 and P2 waves. The sLORETA dipolar analysis was also applied. We evaluated 15 healthy subjects as controls. ResultsWe observed reduced amplitude of the P2 component in FM group, without a topographic correspondence with the prevalent site of denervation. Decreased habituation of P2 prevailed in patients with reduced IENFD. The cingulate cortex and prefrontal cortex, were activated in the FM group, without correlation between the degree of denervation and the strength of late wave dipoles. A correlation was noted between anxiety, depression, fibromyalgia invalidity, and pain diffusion. ConclusionsThe amplitude and topography of LEPs were not coherent with epidermal nerve fiber density loss. They supposedly reflected the clinical expression of pain and psychopathological factors. SignificanceMultichannel LEPs are not the expression of small fiber impairment in FM. Rather, they reflect the complexity of the disease.

Laser-evoked potentials recover gradually when using dorsal root ganglion stimulation, and this influences nociceptive pathways in neuropathic pain patients.

Dorsal root ganglion stimulation (DRGS) is able to relieve chronic neuropathic pain. There seems evidence that DRGS might achieve this by gradually influencing pain pathways. We used laser-evoked potentials (LEP) to verify our hypothesis that the recovery of the LEP may reflect DRGS-induced changes within the nociceptive system. Nine patients (mean age 56.8years, range 36-77years, two females) diagnosed with chronic neuropathic pain in the knee or groin were enrolled in the study. We measured each patient's LEP at the painful limb and contralateral control limb on the first, fourth, and seventh day after implantation of the DRGS system. We used the numeric rating scale (NRS) for the simultaneous pain assessment. The LEP amplitude of the N2-P2 complex showed a significant increase on day 7 when compared to day 1 (Z=-2.666, p=0.008) and to day 4 (Z=-2.547, p=0.011), respectively. There was no significant difference in the N2-P2 complex amplitude between ON and OFF states during DRGS. The patients' NRS significantly decreased after 1day (p=0.007), 4days (p=0.007), and 7days (p=0.007) when compared to the baseline. The results show that with DRGS, the LEP recovered gradually within 7days in neuropathic pain patients. Therefore, reduction of the NRS in patients with chronic neuropathic pain might be due to DRGS-induced processes within the nociceptive system. These processes might indicate neuroplasticity mediated recovery of the LEP.

Segmental Chiropractic Spinal Manipulation Does not Reduce Pain Amplification and the Associated Pain-Related Brain Activity in a Capsaicin-Heat Pain Model.

Musculoskeletal injuries lead to sensitization of nociceptors and primary hyperalgesia (hypersensitivity to painful stimuli). This occurs with back injuries, which are associated with acute pain and increased pain sensitivity at the site of injury. In some cases, back pain persists and leads to central sensitization and chronic pain. Thus, reducing primary hyperalgesia to prevent central sensitization may limit the transition from acute to chronic back pain. It has been shown that spinal manipulation (SM) reduces experimental and clinical pain, but the effect of SM on primary hyperalgesia and hypersensitivity to painful stimuli remains unclear. The goal of the present study was to investigate the effect of SM on pain hypersensitivity using a capsaicin-heat pain model. Laser stimulation was used to evoke heat pain and the associated brain activity, which were measured to assess their modulation by SM. Eighty healthy participants were recruited and randomly assigned to one of the four experimental groups: inert cream and no intervention; capsaicin cream and no intervention; capsaicin cream and SM at T7; capsaicin cream and placebo. Inert or capsaicin cream (1%) was applied to the T9 area. SM or placebo were performed 25 min after cream application. A series of laser stimuli were delivered on the area of cream application (1) before cream application, (2) after cream application but before SM or placebo, and (3) after SM or placebo. Capsaicin cream induced a significant increase in laser pain (p < 0.001) and laser-evoked potential amplitude (p < 0.001). However, SM did not decrease the amplification of laser pain or laser-evoked potentials by capsaicin. These results indicate that segmental SM does not reduce pain hypersensitivity and the associated pain-related brain activity in a capsaicin-heat pain model.

Disruption of working memory and contralateral delay activity by nociceptive stimuli is modulated by task demands.

Top-down processes allow the selection and prioritization of information by limiting attentional capture by distractors, and these mechanisms depend on task demands such as working memory (WM) load. However, bottom-up processes give salient stimuli a stronger neuronal representation and provoke attentional capture. The aim of this study was to examine the effect of salient nociceptive stimuli on WM while manipulating task demands. Twenty-one healthy participants performed a change detection task during which they had to determine whether 2 successive visual arrays were different or the same. Task demands were modulated by manipulating the WM load (set size included 2 or 4 objects to recall) and by the correspondence between the 2 successive visual arrays (change vs no change). Innocuous stimuli (control) or nociceptive stimuli (distractors) were delivered during the delay period between the 2 visual arrays. Contralateral delay activity and laser-evoked potentials were recorded to examine neural markers of visual WM and nociceptive processes. Nociceptive stimuli decreased WM performance depending on task demands (all P < 0.05). Moreover, compared with control stimuli, nociceptive stimuli abolished the increase in contralateral delay activity amplitude for set size 4 vs set size 2 (P = 0.04). Consistent with these results, laser-evoked potential amplitude was not decreased when task demands were high (P = 0.5). These findings indicate that WM may shield cognition from nociceptive stimuli, but nociceptive stimuli disrupt WM and alter task performance when cognitive resources become insufficient to process all task-relevant information.

Paving the way for a better management of pain in patients with spinal cord injury: An exploratory study on the use of Functional Electric Stimulation(FES)-cycling

Context/objective: Chronic pain is common in patients with spinal cord injury (SCI), for whom it negatively affects quality of life, and its treatment requires an integrated approach. To this end, lower limb functional electrical stimulation (FES) cycling holds promise. Objective: To investigate pain reduction in a sample of patients with SCI by means of lower limb rehabilitation using FES cycling. Design, setting and participants: Sixteen patients with incomplete and complete SCIs, attending the Neurorobotic Unit of our research institute and reporting pain at or below the level of their SCI were recruited to this exploratory study. Interventions: Patients undertook two daily sessions of FES cycling, six times weekly, for 6 weeks. Outcome measures: Pain outcomes were measured using the 0–10 numerical rating scale (NRS), the Multidimensional Pain Inventory for SCI (MPI-SCI), and the 36-Item Short Form Survey (SF-36). Finally, we assessed the features of dorsal laser-evoked potentials (LEPs) to objectively evaluate Aδ fiber pathways. Results: All participants tolerated the intervention well, and completed the training without side effects. Statistically significant changes were found in pain-NRS, MPI-SCI, and SF-36 scores, and LEP amplitudes. Following treatment, we found that three patients experienced high pain relief (an NRS decrease of at least 80%), six individuals achieved moderate pain relief (an NRS decrease of about 30–70%), and five participants had mild pain relief (an NRS decrease of less than 30%). Conclusion: Our preliminary results suggest that FES cycling training is capable of reducing the pain reported by patients with SCI, regardless of American Spinal Injury Association scoring, pain level, or the neurological level of injury. The neurophysiological mechanisms underlying such effects are likely to be both spinal and supraspinal.

Revealing the time course of laser-evoked potential habituation by high temporal resolution analysis.

Reduced laser-evoked potential (LEP) habituation indicates abnormal central pain processing. But the paradigm (four stimulation blocks a 25 stimuli) is time consuming and potentially omits important information on the exact habituation time course. This study examined whether a high temporal resolution (HTR) analysis (dividing the four stimulation blocks into 12 analysis blocks) can answer the following questions: (a) After how many stimuli does LEP habituation occur? (b) Is there a difference in LEP habituation in younger versus older subjects? (c) Is HTR applicable on radiculopathy patients? EEG data of 129 subjects were included. Thirty-four young healthy and 28 advanced-aged healthy subjects were tested with LEPs on the hand dorsum. Thirty-seven radiculopathy patients and 30 controls were tested with LEPs on the L3 dermatome. The EEG data of the hand dorsa have been analysed conventionally and with HTR analysis. The applicability of HTR has been tested on radiculopathy patients and respective controls. HTR was well feasible in young healthy subjects and revealed a strong habituation effect during the first 25 stimuli (i.e. within the first 5min). After approximately 48 stimuli, no further significant habituation was detectable. LEP amplitudes were higher in young subjects. HTR was unsuitable for elderly subjects and middle-aged radiculopathy patients. In young healthy subjects, HTR allows a shortening of the test protocol while providing a detailed information on the time course of LEP habituation. A shorter protocol might be useful for the applicability of the LEP paradigm for clinical and experimental settings as well as pharmacological studies. The usage of high temporal resolution (HTR) analysis in young healthy subjects enables a short test protocol and provides the exact time course of laser-evoked potential habituation. This can be useful for the examination of neurological conditions affecting younger patients and for pharmacological studies. HTR was inapplicable in advanced-aged subjects and patients with radiculopathy.

Inhibition of cortical somatosensory processing during and after low frequency peripheral nerve stimulation in humans

ObjectiveTranscutaneous low-frequency stimulation (LFS) elicits long-term depression-like effects on human pain perception. However, the neural mechanisms underlying LFS are poorly understood. We investigated cortical activation changes occurring during LFS and if changes were associated with reduced nociceptive processing and increased amplitude of spontaneous cortical oscillations post-treatment. MethodsLFS was applied to the radial nerve of 25 healthy volunteers over two sessions using active (1 Hz) or sham (0.02 Hz) frequencies. Changes in resting electroencephalography (EEG) and laser-evoked potentials (LEPs) were investigated before and after LFS. Somatosensory-evoked potentials were recorded during LFS and source analysis was carried out. ResultsIpsilateral midcingulate and operculo-insular cortex source activity declined linearly during LFS. Active LFS was associated with attenuated long-latency LEP amplitude in ipsilateral frontocentral electrodes and increased resting alpha (8–12 Hz) and beta (16–24 Hz) band power in electrodes overlying operculo-insular, sensorimotor and frontal cortical regions. Reduced ipsilateral operculo-insular cortex source activity during LFS correlated with a smaller post-treatment alpha-band power increase. ConclusionsLFS attenuated somatosensory processing both during and after stimulation. SignificanceResults further our understanding of the attenuation of somatosensory processing both during and after LFS.

Homotopic reduction in laser-evoked potential amplitude and laser-pain rating by abdominal acupuncture.

The neural mechanism underlying the analgesic effect of acupuncture is largely unknown. We aimed at investigating the effect of abdominal acupuncture (AA) on the laser-evoked potential (LEP) amplitude and laser-pain rating to stimulation of body parts either homotopic or heterotopic to the treated acupoint. Laser-evoked potentials were recorded from 13 healthy subjects to stimulation of the right wrist (RW), left wrist (LW) and right foot (RF). LEPs were obtained before, during and after the AA stimulation of an abdominal area corresponding to the representation of the RW. Subjective laser-pain rating was collected after each LEP recording. The amplitude of the N2/P2 LEP component was significantly reduced during AA and 15min after needle removal to both RW (F=4.14, p=.02) and LW (F=5.48, p=.008) stimulation, while the N2/P2 amplitude to RF stimulation (F=0.94, p=.4) remained unchanged. Laser-pain rating was reduced during AA and 15min after needle removal only to RW stimulation (F=5.67, p=.007). Our findings showing an AA effect on LEP components to both the ipsilateral and contralateral region homotopic to the treated area, without any LEP change to stimulation of a heterotopic region, suggest that the AA analgesia is mediated by a segmental spinal mechanism. Although abdominal acupuncture has demonstrated to be effective in the reduction in laser-evoked potential (LEP) amplitude and laser-pain rating, the exact mechanism of this analgesic effect is not known. In the current study, we found that treatment of an area in the "turtle representation" of the body led to a topographical pattern of LEP amplitude inhibition that can be mediated by a segmental spinal mechanism.

Peripheral and central nervous system correlates in fibromyalgia

Fibromyalgia (FM) is a syndrome characterized by altered pain processing at central and peripheral level, whose pathophysiologic mechanisms remain obscure. We aimed at exploring the structural changes of peripheral nociceptor measured by skin biopsy, the functional changes of central nociceptive pathway assessed by laser-evoked potentials (LEP), and their correlation with clinical features and comorbidities. In all, 81 patients diagnosed with FM underwent skin biopsies with quantification of intraepidermal nerve fibre density (IENFD) at the thigh and distal leg, and LEP recording by stimulating hand, thigh and foot. Nerve conduction study (NCS), clinical features, comorbidity with migraine and mood disorders, and previous, non-active immune-mediated disorders were recorded. Intraepidermal nerve fibre density was reduced in 85% of patients at the thigh and in 12.3% of patients at the distal leg, whereas it was normal in 14.8% of patients. N2P2 habituation index from laser stimulation at the thigh was altered in 97.5% of patients and correlated with reduced IENFD at the thigh. LEP latencies and amplitudes did not differ among groups. No association was found between IENFD, LEP, clinical features and comorbidities. Fibromyalgia patients most commonly showed a mild loss of peripheral nociceptors at the thigh rather than distal small fibre neuropathy. This finding was associated with an altered habituation index and strengthened the hypothesis that central sensitization plays a key role in the pathogenesis of the disease. Central impairment of pain processing likely underlies FM, which in most patients is associated with mild proximal small fibre pathology.

Does Motor Cortex Engagement During Movement Preparation Differentially Inhibit Nociceptive Processing in Patients with Chronic Whiplash Associated Disorders, Chronic Fatigue Syndrome and Healthy Controls? An Experimental Study.

Background: Patients with chronic fatigue syndrome (CFS) and chronic whiplash associated disorders (cWAD) present a reduced ability to activate central descending nociceptive inhibition after exercise, compared to measurements before exercise. It was hypothesised that a dysfunctional motor-induced inhibition of nociception partly explains this dysfunctional exercise-induced hypoalgesia. This study investigates if engagement of the motor system during movement preparation inhibits nociception-evoked brain responses in these patients as compared to healthy controls (HC). Methods: The experiment used laser-evoked potentials (LEPs) during three conditions (no task, mental task, movement preparation) while recording brain activity with a 32-channel electroencephalogram in 21 patients with cWAD, 20 patients with CFS and 18 HC. Two-factor mixed design Analysis of variance were used to evaluate differences in LEP amplitudes and latencies. Results: No differences in N1, N2, N2P2, and P2 LEP amplitudes were found between the HC, CFS, and cWAD groups. After nociceptive stimulation, N1, N2 (only at hand location), N2P2, and P2 LEP amplitudes significantly decreased during movement preparation compared to no task (within group differences). Conclusion: Movement preparation induces a similar attenuation of LEPs in patients with CFS, patients with cWAD and HC. These findings do not support reduced motor-induced nociceptive inhibition in these patients.

Do nociceptive stimulation intensity and temporal predictability influence pain-induced corticospinal excitability modulation?

Temporal predictability and intensity of an impending nociceptive input both shape pain experience and modulate laser-evoked potentials (LEPs) amplitude. However, it remains unclear whether and how these two factors could influence pain-induced corticospinal excitability modulation. The current study investigated the influence of nociceptive stimulation intensity and temporal predictability on motor-evoked potentials (MEPs) modulation, in parallel to their effect on pain perception and LEPs amplitude. Twenty participants completed electroencephalographic and transcranial magnetic stimulation experiments during which two laser nociceptive stimulation intensities (high and low) were either unpredictably delivered (random delay) or preceded by a fixed-timing cue (fixed delay). The amplitude of the conditioned MEPs was significantly reduced only for the high nociceptive stimulation and was not affected by the temporal predictability of pain (despite the fact that temporal predictability modulated the amplitude of P2 LEP component amplitude). However, a posteriori analyses based on patterns of pain-induced MEPs modulation revealed that participants in which nociceptive stimulation resulted in an increase in corticospinal excitability were more affected by the predictability of pain (i.e. increasing corticospinal excitability even more when pain occurrence was predictable), regardless of the nociceptive stimulation intensity; whereas participants in which nociceptive stimulation resulted in a decrease in corticospinal excitability were sensitive to the intensity of the stimulation but not its predictability. These results suggest a potential influence of cognitive factors such as temporal predictability on the response of the motor system in the presence of pain for some participants, contributing to explain, at least in part, the high variability highlighted in a number of previous studies.

ZNRD1-AS and RP11-819C21.1 long non-coding RNA changes following painful laser stimulation correlate with laser-evoked potential amplitude and habituation in healthy subjects: A pilot study.

Non-coding RNAs (lncRNAs) are a group of non-coding RNAs that act as regulators of gene expression; they are implicated in various human diseases and have been reported to be involved in the modulation of pain. We aimed to study whether: (a) lncRNAs modifications could be found in an experimental model of pain; (b) there was a correlation between lncRNA changes and laser evoked potential (LEP) amplitude/laser-pain rating. Laser evoked potentials were recorded from 11 healthy subjects to both left hand and perioral region stimulation. Three consecutive averages were calculated for each stimulation site in order to investigate the LEP amplitude habituation. Blood samples were obtained immediately before LEP recording (pre-pain) and 30-min after the recording of the last LEP average (post-pain). Eighty-four lncRNAs, involved in autoimmunity and human inflammatory response, were screened. The criteria used for lncRNAs analysis were fold change >2 and p<.05. By Real-Time PCR, we identified two lncRNAs up-regulated at the post-pain time, as compared to the pre-pain time: RP11-819C21.1 (fold change=8.2; p=.038) and ZNRD1 antisense RNA 1 non-protein coding (ZNRD1-AS; fold change=6.3; p=.037). The ZNRD1-AS up-regulation was directly correlated with the N1 amplitude, while the RP11-819C21.1 increase after pain showed a correlation with the reduced N2/P2 amplitude and laser-pain habituation. IncRNA changes in a human experimental phasic pain model. The correlation between lncRNA changes and LEP amplitude and habituation suggests that RP11-819C21.1 and ZNRD1-AS could be involved in the pathophysiology of painful diseases characterized by abnormal excitability of the cerebral cortex. Long non-coding RNAs are upregulated after experimental pain. RP11-819C21.1 and ZNRD1 could be involved in the pathophysiology of diseases characterized by reduced habituation to pain.

P80-S Transspinal direct current stimulation for pain treatment. Objective proof of concept and initial clinical findings

Background Neuropathic pain is a large clinical problem, not least such pain affecting lower extremities. Transspinal Direct Current Stimulation (tsDCS) has been reported, with varying results, to block afferent nerve signaling from lower extremities. To address this uncertainty and to approach a potential clinical usage, two studies were performed. Materials and methods Study I - In nineteen healthy controls, the anode was placed over the tenth thoracic vertebra, the cathode over the shoulder. tsDCS: 2.5 A for 20 min, double blinded cross over design. Laser Evoked Potentials (LEPs): Stimulation of the dorsum of the hand and foot respectively, recordings at baseline, immediately after- and 30 min after the tsDCS stimulation. Amplitude and latency of the N2 peak was assessed and the subjects rated pain intensities using a visual analog scale. Study II - Patients with neuropathic pain due to polyneuropathy are recruited. tsDCS is given as above. Results Study I - Group level: LEP amplitudes were successively reduced over time. Placebo stimulation; latencies unaffected from upper-, slightly increased from lower extremities. Verum stimulation; transiently increased from upper-, accumulatively increased from lower extremities in proportion to the experienced pain. Individual level: Large variations. Study II - At present, four patients have been investigated. The results from these and a larger group will be presented at the conference. Conclusions LEP amplitude is an unreliable parameter for evaluating transspinal pain signaling. Short term, anodal thoracic tsDCS affects transspinal pain signaling with large inter-individual differences. Individualized tsDCS may be one of the treatment options for neuropathic pain.

Neurophysiological Effects of Dorsal Root Ganglion Stimulation (DRGS) in Pain Processing at the Cortical Level

Dorsal root ganglion stimulation (DRGS) has been used successfully against localized neuropathic pain. Nevertheless, the effects of DRGS on pain processing, particularly at the cortical level, remain largely unknown. In this study, we investigated whether positive responses to DRGS treatment would alter patients' laser-evoked potentials (LEP). We prospectively enrolled 12 adult patients with unilateral localized neuropathic pain in the lower limbs or inguinal region and followed them up for six months. LEPs were assessed at baseline, after one month of DRGS, and after six months of DRGS. Clinical assessment included the Numerical Rating Scale (NRS), Brief Pain Inventory (BPI), SF-36, and Beck Depression Inventory (BDI). For each patient, LEP amplitudes and latencies of the N2 and P2 components on the deafferented side were measured and compared to those of the healthy side and correlated with pain intensity, as measured with the NRS. At the one- and six-month follow-ups, N2-P2 amplitudes were significantly greater and NRS scores were significantly lower compared with baseline (all p's < 0.01). There was a negative correlation between LEP amplitudes and NRS scores (rs = -0.31, p < 0.10). DRGS is able to restore LEPs to normal values in patients with localized neuropathic pain, and LEP alterations are correlated with clinical response in terms of pain intensity.

Neurophysiological Comparison Among Tonic, High Frequency, and Burst Spinal Cord Stimulation: Novel Insights Into Spinal and Brain Mechanisms of Action

Spinal cord stimulation (SCS) is an effective option for neuropathic pain treatment. New technological developments, as high-frequency (HF) and theta burst stimulation (TBS), have shown promising results, although putative mechanisms of action still remain debated. thirty patients with lower back pain were enrolled and underwent LF, HF, and TBS. Laser evoked potentials (LEPs) were recorded by using a Nd:YAG laser. Amplitudes and latencies of the main two components (N1, N2/P2) were compared among different experimental sessions. Changes in resting motor threshold (RMT), cortical silent period (cSP), short intracortical inhibition (SICI), and intracortical facilitation (ICF) were also evaluated. TBS dampened LEP amplitudes compared with LF (N1: p = 0.032; N2/P2: p < 0.0001) and HF stimulation (N1: p = 0.029; N2/P2: p < 0.0001, Holm-Sidak post-hoc test). Concurrently, TBS increased N1 latency, when compared with baseline and LF stimulation (p = 0.009 and 0.0033). Whereas RMT and SICI did not change among experimental conditions, TBS significantly prolonged cSP duration compared with baseline (p = 0.002), LF (p = 0.048), and HF-SCS (p = 0.016); finally, both HF (p = 0.004) and TBS (p = 0.0039) increased ICF. TBS modulates medial and lateral pain pathways through distinct mechanisms, possibly involving both GABA(a)ergic and Glutamatergic networks at an intracortical level. These results may have implications for therapy and for the choice of best stimulation protocol.

S154. Effect of transspinal direct current stimulation on afferent pain signaling in humans

Introduction Neuropathic pain is a large clinical problem, not least such pain affecting lower extremities. Transspinal Direct Current Stimulation (tsDCS) has been reported to block afferent nerve signaling from lower extremities. However, the results vary between studies. Our aim was to study this neuromodulatory technique using a published stimulation paradigm under strict methodological control. This could reveal whether tsDCS might be developed into a treatment option for neuropathic pain. Methods Nineteen healthy young adults of both sexes were investigated. The anode was placed over the tenth thoracic vertebra, the cathode over the shoulder opposed to the side stimulated with laser light. tsDCS was given with 2.5 A for 20 min using a double blinded (verum vs. placebo), cross over design. Laser Evoked Potentials (LEPs) were evoked by stimulation of the dorsum of the hand and foot respectively on the dominating side. Recordings were made from standard scalp positions. LEPs were recorded at three time points: at baseline, immediately after- and 30 min after the tsDCS stimulation. Amplitude and latency of the N2 peak was assessed and the subjects rated the pain intensity using a visual analog scale. Results Reliable recordings were achieved from 17/19 subjects. No long standing discomfort was reported. At the group level, LEP amplitudes were successively reduced over time, more for stimulation of lower- than for upper extremities, irrespective of type of tsDCS stimulation. With placebo stimulation, latencies were unaffected from upper- and slightly increased from lower extremities. With verum stimulation, they were transiently increased from upper-, accumulatively increased from lower extremities. The intensity of the pain experienced from the laser stimulation was related to LEP latency. At the individual level, the degree to which LEP parameters were affected by tsDCS varied widely. Conclusion LEP amplitude is an unreliable parameter for evaluating transspinal pain signaling. Short term, anodal thoracic tsDCS may affect transspinal pain signaling as assessed by LEP latency. The degree to which this happens shows large inter-individual difference. Alternative stimulation paradigms may have larger effect. After further evaluation and optimization, tsDCS may be one of the treatment options for neuropathic pain e.g. in polyneuropathy and during child labor. If so, individualization seems to be necessary.

69. Abdominal acupuncture reduces pain at the spinal cord 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 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; and (3) rest, in which LEPs were recorded 15 min after the needle removal. 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. 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.