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S112 LASER-INDUCED GAMMA OSCILLATIONS ROBUSTLY CORRELATE WITH PAIN PERCEPTION REGARDLESS OF STIMULUS SALIENCY
POSTER SESSIONS / European Journal of Pain Supplements 5 (2011) 15–295
S110 THE DEFENSIVE BLINK REFLEX EVOKED BY HAND STIMULATION IS INCREASED WHEN THE HAND ENTERS THE PERIPERSONAL SPACE SURROUNDING THE FACE C. Sambo1 *, M. Liang1 , G. Cruccu2 , G.D. Iannetti1 . 1 Neuroscience, Physiology, and Pharmacology, University College London, London, UK; 2 Department of Neurology and Psychiatry, La Sapienza University, Rome, Italy Background and Aims: Electrical stimulation of the hand may elicit a blink reflex (HBR) mediated by a neural circuit at brainstem level. As, in a Sherringtonian sense, the blink reflex is a defensive response, in six experiments we tested whether and how the HBR is modulated by the proximity of the stimulated hand to the face. Methods: Electrical stimuli were applied to the median nerve at the wrist (or to the supraorbital nerve) while the stimulated hand was inside or outside the peripersonal space surrounding the face. Electromyographic activity was recorded from the orbicularis oculi, bilaterally. Results: The HBR is enhanced in a graded fashion when the stimulated hand gets closer to the peripersonal space of the face. This enhancement is independent of whether (1) the participants have their eyes open and closed, and (2) the proximity of the hand to the face is manipulated by changing the position of the arm or by rotating the head while keeping the arm position constant. In contrast, the N20 wave of the somatosensory evoked potentials elicited by median nerve stimulation, as well as the blink reflex elicited by supraorbital nerve stimulation are entirely unaffected by hand position.
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for encoding the location of somatosensory stimuli in external space coordinates. Disclosure: None declared
S111 COGNITIVE MODULATION OF THE EXCITABILITY OF BRAINSTEM DEFENSIVE REFLEXES C. Sambo1,2 *, B. Forster2 , S. Williams3 , G.D. Iannetti1 . 1 Neuroscience, Physiology, and Pharmacology, University College London, 2 Psychology Department, City University London, 3 Neuroimaging, King’s College London, Institute of Psychiatry, London, UK Background and Aims: We have previously shown that the blink reflex elicited by the electrical stimulation of the hand (HBR) is dramatically enhanced when the stimulated hand enters the peripersonal space of the face. Here, we investigated whether this effect is influenced by cognitive expectations. Methods: Electrical stimuli were applied to the median nerve at the wrist while the hand was either inside or outside the peripersonal space surrounding the face (‘near’ vs. ‘far’). In Experiment 1, a screen was placed between the participants’ face and the hand undergoing the ‘near’ and ‘far’ manipulation. In Experiments 2, the HBR was elicited by the stimulation of either the hand undergoing the ‘near’ and ‘far’ manipulation or the contralateral hand, which was always kept in the ‘far’ position. In Experiment 3, only the hand contralateral to the one undergoing the ‘near’ and ‘far’ manipulation was stimulated. Results: The HBR enhancement by hand position was (1) abolished when the screen was interposed between the participants’ face and their hand, (2) significantly reduced in the response elicited by the stimulation of the hand contralateral to the one placed near the face, and (3) abolished when stimuli were only delivered to the hand always kept in the ‘far’ position. Conclusions: These findings that that the brainstem circuits mediating the HBR are modulated by cognitive expectations indicate that the nervous system is able to adjust its output in a very specific and fine-grained manner, even at the level of seemingly stereotyped reflex responses. Disclosure: None declared
S112 LASER-INDUCED GAMMA OSCILLATIONS ROBUSTLY CORRELATE WITH PAIN PERCEPTION REGARDLESS OF STIMULUS SALIENCY L. Hu1,2 *, Z.G. Zhang3,4 , Y. Hu2 , Y.S. Hung4 , A. Mouraux5 , G.D. Iannetti3 . 1 Key Laboratory of Cognition and Personality (Ministry of Education) and School of Psychology, Southwest University, Chongqing, 2 Department of Orthopaedics and Traumatology, The University of Hong Kong, Hong Kong, China; 3 Department of Neuroscience, Physiology and Pharmacology, University College London, London, UK; 4 Department of Electrical and Electronic Engineering, The University of Hong Kong, Hong Kong, China; 5 Institute of Neuroscience, Universit´e catholique de Louvain, Brussels, Belgium
Figure: HBR modulation by hand position.
Conclusions: These findings provide compelling evidence that the brainstem circuits mediating the HBR undergo tonic and selective top-down modulation from higher-order cortical areas responsible
Background and Aims: In most experimental conditions, the magnitude of different features of the laser-evoked EEG responses (the phase-locked N1, N2 and P2 waves, and the non-phase-locked modulation of low-frequency (<40 Hz) oscillations) correlates robustly with the intensity of pain perception. However, when identical laser stimuli are presented at a short and constant interstimulus interval (e.g. 1 s) this correlation is markedly disrupted. As laser-induced gamma band oscillations (>40 Hz) have been recently suggested to be related to the subjective perception of pain, here we investigated whether they are able to maintain a robust correlation with the intensity of pain perception even when laser stimuli are repeated. Methods: EEG responses were elicited by trains of three identical laser pulses delivered to the hand dorsum using a constant 1 s inter-stimulus interval and four different energies. The modulation
200
POSTER SESSIONS / European Journal of Pain Supplements 5 (2011) 15–295
exerted by stimulus repetition and intensity of pain perception on the laser-induced time-frequency responses was tested using pointby-point, two-way, repeated-measures ANOVA and permutation testing. Results: The magnitude of laser-induced gamma oscillations (>40 Hz) was significantly and positively correlated with the intensity of pain perception, and, crucially, not significantly modulated by stimulus repetition. The magnitude of such gamma oscillations was maximal the central electrodes contralateral to the stimulated hand (e.g. C3 and C4). Conclusions: Laser-induced gamma oscillations correlate with the intensity of pain perception even when the saliency content of the eliciting stimulus is reduced by stimulus repetition. Thus, they represent the feature of the laser-elicited EEG response that best relates to the intensity of perceived pain. Disclosure: None declared
S113 IMPAIRED WORKING MEMORY PERFORMANCE IN NEUROPATHIC RATS IS ACCOMPANIED BY REDUCED FLOW OF INFORMATION IN THE FRONTOHIPPOCAMPAL PATHWAY V. Galhardo1,2 *, H. Cardoso-Cruz1 , D. Lima1 . 1 Departamento Biologia Experimental, Faculdade de Medicina, 2 IBMC – Instituto Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal Background and Aims: Performance in working memory tasks is impaired by lesions to either the medial prefrontal contral (mPFC) or the hippocampus (CA1) although how these two areas contribute to successful performance is not well understood. To address the effect of prolonged pain on working memory circuitry, we chronically implanted arrays of multielectrodes in the mPFC and dorsal hippocampus to record neuronal activity during a food reinforced spatial alternation task in a figure-eight runway. Methods: Recordings of neural activity were performed over a three week period before and after the establishment of neuropathic spared nerve injury model (SNI). Data included LFP signals and spiking activity from 175 neurons recorded in 10 male adult rats. Results: Our results showed a clear decrease in performance after peripheral nerve injury. The perievents time histograms of the spiking frequencies for correct and error trials, revealed no differences in the percentage of neurons with altered activity across correct trials, while for error trials a significant increase was evident in CA1 neurons. In addition, both recorded areas presented a different tuning phase of correlation between spiking activity and hippocampal theta rhythm during the delay period after lesion. Partial directed coherence – PDC – revealed that after lesion the volume of information transmitted across the mPFC-CA1 pathway was significantly reduced in both directions. Conclusions: The present results demonstrate that peripheral nerve lesion leads to disturbances in the functional mPFC-CA1 circuit probably caused by working memory deficits. Supported by FCT Grants SFRH/BD/42500/2007, PTDC/SAUNEU/100773/2008, BIAL Foundation Grant 126/08. Disclosure: None declared
S114 INTER-RELATIONS BETWEEN OFFSET ANALGESIA (OA) AND CONDITIONED PAIN MODULATION (CPM) L. Honigman1 *, I. Weissman-Fogel2 , D. Yarnitsky1 . 1 Department of Neurology, Rambam Health Care Campus, and The Laboratory of Clinical Neurophysiology, Faculty of Medicine, Technion – Israel Institute of Technology, 2 Faculty of Social Welfare and Health Sciences, University of Haifa, Haifa, Israel Background and Aims: Pain modulation can be evaluated psychophysically in different dimensions; conditioned pain modulation (CPM) expressing spatial filtering, and offset analgesia (OA) expressing temporal filtering. We examined the inter-relations
and possible accumulation effect between these paradigms, asking whether they are sub-served by a single mechanism. Methods: 29 healthy subjects (14 women) underwent 4 series of thermal stimuli, in random order: OA evoked by threetemperature stimulus train (T1 = 49, T2 = 50, T3 = 49°C; 5 s, 5 s, 20 s respectively), 30 s constant 49°C stimulus (‘control train’) and two CPM paradigms (30 s of OA or constant 49°C stimulus given alone and simultaneously with immersion of the other hand in hot water). Differences in pain rating between (i) T1 and T3 in the OA train, and (ii) before and during immersion for the CPM paradigms, both versus the ‘control train’, were taken as OA and CPM effects, respectively. Results: A correlation was found between OA and CPM (r = 0.59, P = 0.000) at the maximum OA effect. For simultaneous activation of OA+CPM a nearly significant additive effect was found (P = 0.056). Conclusions: Correlation between OA and CPM suggests similar mechanism for the two. However, accumulation of the magnitude of pain inhibition implies some differences. It might be that while both activate brainstem analgesia centers, the spino-bulbar-spinal tonic pain inhibition evoked via CPM, is further improved by the short offset stimulus possibly evoking a phasic activity in the cerebral pain gate-keepers amygdala and accumbens. The ability to augment pain inhibition by simple means of stimulus manipulation is of importance in future pain treatment. Disclosure: None declared
S115 ARE NOCICEPTIVE CORTICAL RESPONSES NECESSARILY RELAYED THROUGH THE PRIMARY SOMATOSENSORY CORTEX? D.M. Torta1,2 *, V. Legrain1,3 , J. Duque´ 1 , E. Olivier1 , A. Mouraux1 . 1 Institute of Neuroscience (IONS), Universit´e catholique de Louvain, Brussel, Belgium; 2 Department of Psychology, University of Turin, Torino, Italy; 3 Department of Experimental and Clinical Health Psychology, Ghent University, Ghent, Belgium Background and Aims: Whether or not the contralateral primary somatosensory cortex (S1) constitutes the first and obligatory relay for the cortical processing of both non-nociceptive and nociceptive somatosensory inputs is debated. We addressed this question by examining the effect of temporarily inhibiting S1 using continuous theta burst stimulation (cTBS) on non-nociceptive and nociceptive somatosensory event-related potentials (SEPs). Methods: Non-nociceptive (transcutaneous median nerve stimulation) and nociceptive (CO2 laser stimulation of the hand dorsum) SEPs were recorded following stimulation of the left and right hand, before and after applying cTBS over the left or right S1 (localized using coregistration of individual MRI data). For each of the different peaks characterizing late non-nociceptive and nociceptive SEPs, the finding of an interaction between the factors ‘session’ (before vs. after cTBS) and ‘side’ (stimuli applied ipsilateral vs. contralateral to the hemisphere onto which cTBS was applied) was considered as evidence that S1 constitutes an obligatory relay for their generation. Results: Eleven subjects participated in the study. The N20 of nonnociceptive SEPs, known to originate from S1, was reduced when stimuli were applied contralateral to the conditioned hemisphere (p = 0.038), thus confirming the effectiveness of cTBS at modulating S1 responsiveness. In contrast, no interaction was found for the later components of non-nociceptive (e.g. N140 and P200) and nociceptive (N240 and P350) SEPs. Conclusions: These results indicate that S1 does not constitute an obligatory relay for the late cortical responses of both nonnociceptive and nociceptive SEPs, hypothesized to originate mainly from S2, the insula and the ACC. Disclosure: None declared
S110 THE DEFENSIVE BLINK REFLEX EVOKED BY HAND STIMULATION IS INCREASED WHEN THE HAND ENTERS THE PERIPERSONAL SPACE SURROUNDING THE FACE C. Sambo1 *, M. Liang1 , G. Cruccu2 , G.D. Iannetti1 . 1 Neuroscience, Physiology, and Pharmacology, University College London, London, UK; 2 Department of Neurology and Psychiatry, La Sapienza University, Rome, Italy Background and Aims: Electrical stimulation of the hand may elicit a blink reflex (HBR) mediated by a neural circuit at brainstem level. As, in a Sherringtonian sense, the blink reflex is a defensive response, in six experiments we tested whether and how the HBR is modulated by the proximity of the stimulated hand to the face. Methods: Electrical stimuli were applied to the median nerve at the wrist (or to the supraorbital nerve) while the stimulated hand was inside or outside the peripersonal space surrounding the face. Electromyographic activity was recorded from the orbicularis oculi, bilaterally. Results: The HBR is enhanced in a graded fashion when the stimulated hand gets closer to the peripersonal space of the face. This enhancement is independent of whether (1) the participants have their eyes open and closed, and (2) the proximity of the hand to the face is manipulated by changing the position of the arm or by rotating the head while keeping the arm position constant. In contrast, the N20 wave of the somatosensory evoked potentials elicited by median nerve stimulation, as well as the blink reflex elicited by supraorbital nerve stimulation are entirely unaffected by hand position.
199
for encoding the location of somatosensory stimuli in external space coordinates. Disclosure: None declared
S111 COGNITIVE MODULATION OF THE EXCITABILITY OF BRAINSTEM DEFENSIVE REFLEXES C. Sambo1,2 *, B. Forster2 , S. Williams3 , G.D. Iannetti1 . 1 Neuroscience, Physiology, and Pharmacology, University College London, 2 Psychology Department, City University London, 3 Neuroimaging, King’s College London, Institute of Psychiatry, London, UK Background and Aims: We have previously shown that the blink reflex elicited by the electrical stimulation of the hand (HBR) is dramatically enhanced when the stimulated hand enters the peripersonal space of the face. Here, we investigated whether this effect is influenced by cognitive expectations. Methods: Electrical stimuli were applied to the median nerve at the wrist while the hand was either inside or outside the peripersonal space surrounding the face (‘near’ vs. ‘far’). In Experiment 1, a screen was placed between the participants’ face and the hand undergoing the ‘near’ and ‘far’ manipulation. In Experiments 2, the HBR was elicited by the stimulation of either the hand undergoing the ‘near’ and ‘far’ manipulation or the contralateral hand, which was always kept in the ‘far’ position. In Experiment 3, only the hand contralateral to the one undergoing the ‘near’ and ‘far’ manipulation was stimulated. Results: The HBR enhancement by hand position was (1) abolished when the screen was interposed between the participants’ face and their hand, (2) significantly reduced in the response elicited by the stimulation of the hand contralateral to the one placed near the face, and (3) abolished when stimuli were only delivered to the hand always kept in the ‘far’ position. Conclusions: These findings that that the brainstem circuits mediating the HBR are modulated by cognitive expectations indicate that the nervous system is able to adjust its output in a very specific and fine-grained manner, even at the level of seemingly stereotyped reflex responses. Disclosure: None declared
S112 LASER-INDUCED GAMMA OSCILLATIONS ROBUSTLY CORRELATE WITH PAIN PERCEPTION REGARDLESS OF STIMULUS SALIENCY L. Hu1,2 *, Z.G. Zhang3,4 , Y. Hu2 , Y.S. Hung4 , A. Mouraux5 , G.D. Iannetti3 . 1 Key Laboratory of Cognition and Personality (Ministry of Education) and School of Psychology, Southwest University, Chongqing, 2 Department of Orthopaedics and Traumatology, The University of Hong Kong, Hong Kong, China; 3 Department of Neuroscience, Physiology and Pharmacology, University College London, London, UK; 4 Department of Electrical and Electronic Engineering, The University of Hong Kong, Hong Kong, China; 5 Institute of Neuroscience, Universit´e catholique de Louvain, Brussels, Belgium
Figure: HBR modulation by hand position.
Conclusions: These findings provide compelling evidence that the brainstem circuits mediating the HBR undergo tonic and selective top-down modulation from higher-order cortical areas responsible
Background and Aims: In most experimental conditions, the magnitude of different features of the laser-evoked EEG responses (the phase-locked N1, N2 and P2 waves, and the non-phase-locked modulation of low-frequency (<40 Hz) oscillations) correlates robustly with the intensity of pain perception. However, when identical laser stimuli are presented at a short and constant interstimulus interval (e.g. 1 s) this correlation is markedly disrupted. As laser-induced gamma band oscillations (>40 Hz) have been recently suggested to be related to the subjective perception of pain, here we investigated whether they are able to maintain a robust correlation with the intensity of pain perception even when laser stimuli are repeated. Methods: EEG responses were elicited by trains of three identical laser pulses delivered to the hand dorsum using a constant 1 s inter-stimulus interval and four different energies. The modulation
200
POSTER SESSIONS / European Journal of Pain Supplements 5 (2011) 15–295
exerted by stimulus repetition and intensity of pain perception on the laser-induced time-frequency responses was tested using pointby-point, two-way, repeated-measures ANOVA and permutation testing. Results: The magnitude of laser-induced gamma oscillations (>40 Hz) was significantly and positively correlated with the intensity of pain perception, and, crucially, not significantly modulated by stimulus repetition. The magnitude of such gamma oscillations was maximal the central electrodes contralateral to the stimulated hand (e.g. C3 and C4). Conclusions: Laser-induced gamma oscillations correlate with the intensity of pain perception even when the saliency content of the eliciting stimulus is reduced by stimulus repetition. Thus, they represent the feature of the laser-elicited EEG response that best relates to the intensity of perceived pain. Disclosure: None declared
S113 IMPAIRED WORKING MEMORY PERFORMANCE IN NEUROPATHIC RATS IS ACCOMPANIED BY REDUCED FLOW OF INFORMATION IN THE FRONTOHIPPOCAMPAL PATHWAY V. Galhardo1,2 *, H. Cardoso-Cruz1 , D. Lima1 . 1 Departamento Biologia Experimental, Faculdade de Medicina, 2 IBMC – Instituto Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal Background and Aims: Performance in working memory tasks is impaired by lesions to either the medial prefrontal contral (mPFC) or the hippocampus (CA1) although how these two areas contribute to successful performance is not well understood. To address the effect of prolonged pain on working memory circuitry, we chronically implanted arrays of multielectrodes in the mPFC and dorsal hippocampus to record neuronal activity during a food reinforced spatial alternation task in a figure-eight runway. Methods: Recordings of neural activity were performed over a three week period before and after the establishment of neuropathic spared nerve injury model (SNI). Data included LFP signals and spiking activity from 175 neurons recorded in 10 male adult rats. Results: Our results showed a clear decrease in performance after peripheral nerve injury. The perievents time histograms of the spiking frequencies for correct and error trials, revealed no differences in the percentage of neurons with altered activity across correct trials, while for error trials a significant increase was evident in CA1 neurons. In addition, both recorded areas presented a different tuning phase of correlation between spiking activity and hippocampal theta rhythm during the delay period after lesion. Partial directed coherence – PDC – revealed that after lesion the volume of information transmitted across the mPFC-CA1 pathway was significantly reduced in both directions. Conclusions: The present results demonstrate that peripheral nerve lesion leads to disturbances in the functional mPFC-CA1 circuit probably caused by working memory deficits. Supported by FCT Grants SFRH/BD/42500/2007, PTDC/SAUNEU/100773/2008, BIAL Foundation Grant 126/08. Disclosure: None declared
S114 INTER-RELATIONS BETWEEN OFFSET ANALGESIA (OA) AND CONDITIONED PAIN MODULATION (CPM) L. Honigman1 *, I. Weissman-Fogel2 , D. Yarnitsky1 . 1 Department of Neurology, Rambam Health Care Campus, and The Laboratory of Clinical Neurophysiology, Faculty of Medicine, Technion – Israel Institute of Technology, 2 Faculty of Social Welfare and Health Sciences, University of Haifa, Haifa, Israel Background and Aims: Pain modulation can be evaluated psychophysically in different dimensions; conditioned pain modulation (CPM) expressing spatial filtering, and offset analgesia (OA) expressing temporal filtering. We examined the inter-relations
and possible accumulation effect between these paradigms, asking whether they are sub-served by a single mechanism. Methods: 29 healthy subjects (14 women) underwent 4 series of thermal stimuli, in random order: OA evoked by threetemperature stimulus train (T1 = 49, T2 = 50, T3 = 49°C; 5 s, 5 s, 20 s respectively), 30 s constant 49°C stimulus (‘control train’) and two CPM paradigms (30 s of OA or constant 49°C stimulus given alone and simultaneously with immersion of the other hand in hot water). Differences in pain rating between (i) T1 and T3 in the OA train, and (ii) before and during immersion for the CPM paradigms, both versus the ‘control train’, were taken as OA and CPM effects, respectively. Results: A correlation was found between OA and CPM (r = 0.59, P = 0.000) at the maximum OA effect. For simultaneous activation of OA+CPM a nearly significant additive effect was found (P = 0.056). Conclusions: Correlation between OA and CPM suggests similar mechanism for the two. However, accumulation of the magnitude of pain inhibition implies some differences. It might be that while both activate brainstem analgesia centers, the spino-bulbar-spinal tonic pain inhibition evoked via CPM, is further improved by the short offset stimulus possibly evoking a phasic activity in the cerebral pain gate-keepers amygdala and accumbens. The ability to augment pain inhibition by simple means of stimulus manipulation is of importance in future pain treatment. Disclosure: None declared
S115 ARE NOCICEPTIVE CORTICAL RESPONSES NECESSARILY RELAYED THROUGH THE PRIMARY SOMATOSENSORY CORTEX? D.M. Torta1,2 *, V. Legrain1,3 , J. Duque´ 1 , E. Olivier1 , A. Mouraux1 . 1 Institute of Neuroscience (IONS), Universit´e catholique de Louvain, Brussel, Belgium; 2 Department of Psychology, University of Turin, Torino, Italy; 3 Department of Experimental and Clinical Health Psychology, Ghent University, Ghent, Belgium Background and Aims: Whether or not the contralateral primary somatosensory cortex (S1) constitutes the first and obligatory relay for the cortical processing of both non-nociceptive and nociceptive somatosensory inputs is debated. We addressed this question by examining the effect of temporarily inhibiting S1 using continuous theta burst stimulation (cTBS) on non-nociceptive and nociceptive somatosensory event-related potentials (SEPs). Methods: Non-nociceptive (transcutaneous median nerve stimulation) and nociceptive (CO2 laser stimulation of the hand dorsum) SEPs were recorded following stimulation of the left and right hand, before and after applying cTBS over the left or right S1 (localized using coregistration of individual MRI data). For each of the different peaks characterizing late non-nociceptive and nociceptive SEPs, the finding of an interaction between the factors ‘session’ (before vs. after cTBS) and ‘side’ (stimuli applied ipsilateral vs. contralateral to the hemisphere onto which cTBS was applied) was considered as evidence that S1 constitutes an obligatory relay for their generation. Results: Eleven subjects participated in the study. The N20 of nonnociceptive SEPs, known to originate from S1, was reduced when stimuli were applied contralateral to the conditioned hemisphere (p = 0.038), thus confirming the effectiveness of cTBS at modulating S1 responsiveness. In contrast, no interaction was found for the later components of non-nociceptive (e.g. N140 and P200) and nociceptive (N240 and P350) SEPs. Conclusions: These results indicate that S1 does not constitute an obligatory relay for the late cortical responses of both nonnociceptive and nociceptive SEPs, hypothesized to originate mainly from S2, the insula and the ACC. Disclosure: None declared