45 results on '"Larrea, Luis"'
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2. Personalized pain management: Ready for it?
- Author
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Garcia-Larrea L and Bouhassira D
- Subjects
- Humans, Pain drug therapy, Pain Management
- Published
- 2023
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- View/download PDF
3. Sympathetic skin response as an objective tool to estimate stimulus-associated arousal in a human model of hyperalgesia.
- Author
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Salameh C, Perchet C, Hagiwara K, and Garcia-Larrea L
- Subjects
- Humans, Arousal physiology, Pain Measurement, Capsaicin pharmacology, Skin, Hyperalgesia diagnosis, Pain
- Abstract
Background: Pain is a private experience, whose assessment relies on subjective self-reporting. Inaccurate communication renders pain evaluation unreliable in individuals with alteration of consciousness, lack of verbal interaction, cognitive dysfunction or simple malingering, hence the importance of developing reliable objective assessment tools., Objectives: Since pain is associated with autonomic arousal, here we used readouts of autonomic activity to assess objectively the arousing effect of somatic stimuli in a human model of hyperalgesia., Methods: We used topical capsaicin to induce cutaneous hypersensitivity in the right arm of 20 healthy volunteers, and recorded sympathetic skin responses (SSR) and numerical perceptive ratings (NRS) to stimulation of the sensitized region and its homologous contralateral site, using brush (Aβ), pinprick (Aδ) and laser (C-Warmth) stimuli., Results: Both subjective ratings and SSRs were significantly enhanced to stimulation of the sensitized region, and their respective ratios of maximal enhancement were positively correlated. At individual level, a significant association was observed between SSR and NRS behavior (χ2(1)= 11.03; p < 0.001), with a positive predictive value of 87% (CI95 [77-97%]) for SSR increase predicting enhancement of subjective reports. A "lie experiment" asking subjects to simulate elevated NRS failed to enhance SSRs. Significant habituation of SSRs appeared when stimuli were repeated at ∼15s intervals, hence decreasing their negative predictive value when several consecutive stimuli were averaged (NPV=46%; CI95 [30-62%])., Conclusion: The SSR may represent a rapid and reliable procedure to assess cutaneous hypersensitivity, simple to use in clinical practice and resistant to simulation. Rapid habituation is a drawback that can be countered by using few repetitions and low stimulus rates., Competing Interests: Conflict of interest The authors declare that there are no financial or other relationships that might lead to a conflict of interest., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)
- Published
- 2022
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- View/download PDF
4. IMI2-PainCare-BioPain-RCT2 protocol: a randomized, double-blind, placebo-controlled, crossover, multicenter trial in healthy subjects to investigate the effects of lacosamide, pregabalin, and tapentadol on biomarkers of pain processing observed by non-invasive neurophysiological measurements of human spinal cord and brainstem activity.
- Author
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Leone C, Di Stefano G, Di Pietro G, Bloms-Funke P, Boesl I, Caspani O, Chapman SC, Finnerup NB, Garcia-Larrea L, Li T, Goetz M, Mouraux A, Pelz B, Pogatzki-Zahn E, Schilder A, Schnetter E, Schubart K, Tracey I, Troconiz IF, Van Niel H, Hernandez JMV, Vincent K, Vollert J, Wanigasekera V, Wittayer M, Phillips KG, Truini A, and Treede RD
- Subjects
- Biomarkers, Brain Stem, Cross-Over Studies, Double-Blind Method, Healthy Volunteers, Humans, Lacosamide, Multicenter Studies as Topic, Pregabalin, Randomized Controlled Trials as Topic, Tapentadol, Analgesics pharmacology, Pain drug therapy, Spinal Cord
- Abstract
Background: IMI2-PainCare-BioPain-RCT2 is one of four similarly designed clinical studies aiming at profiling a set of functional biomarkers of drug effects on specific compartments of the nociceptive system that could serve to accelerate the future development of analgesics. IMI2-PainCare-BioPain-RCT2 will focus on human spinal cord and brainstem activity using biomarkers derived from non-invasive neurophysiological measurements., Methods: This is a multisite, single-dose, double-blind, randomized, placebo-controlled, 4-period, 4-way crossover, pharmacodynamic (PD) and pharmacokinetic (PK) study in healthy subjects. Neurophysiological biomarkers of spinal and brainstem activity (the RIII flexion reflex, the N13 component of somatosensory evoked potentials (SEP) and the R2 component of the blink reflex) will be recorded before and at three distinct time points after administration of three medications known to act on the nociceptive system (lacosamide, pregabalin, tapentadol), and placebo, given as a single oral dose in separate study periods. Medication effects on neurophysiological measures will be assessed in a clinically relevant hyperalgesic condition (high-frequency electrical stimulation of the skin), and in a non-sensitized normal condition. Patient-reported outcome measures (pain ratings and predictive psychological traits) will also be collected; and blood samples will be taken for pharmacokinetic modelling. A sequentially rejective multiple testing approach will be used with overall alpha error of the primary analysis split between the two primary endpoints, namely the percentage amplitude changes of the RIII area and N13 amplitude under tapentadol. Remaining treatment arm effects on RIII, N13 and R2 recovery cycle are key secondary confirmatory analyses. Complex statistical analyses and PK-PD modelling are exploratory., Discussion: The RIII component of the flexion reflex is a pure nociceptive spinal reflex widely used for investigating pain processing at the spinal level. It is sensitive to different experimental pain models and to the antinociceptive activity of drugs. The N13 is mediated by large myelinated non-nociceptive fibers and reflects segmental postsynaptic response of wide dynamic range dorsal horn neurons at the level of cervical spinal cord, and it could be therefore sensitive to the action of drugs specifically targeting the dorsal horn. The R2 reflex is mediated by large myelinated non-nociceptive fibers, its circuit consists of a polysynaptic chain lying in the reticular formation of the pons and medulla. The recovery cycle of R2 is widely used for assessing brainstem excitability. For these reasons, IMI2-PainCare-BioPain-RCT2 hypothesizes that spinal and brainstem neurophysiological measures can serve as biomarkers of target engagement of analgesic drugs for future Phase 1 clinical trials. Phase 2 and 3 clinical trials could also benefit from these tools for patient stratification., Trial Registration: This trial was registered on 02 February 2019 in EudraCT ( 2019-000755-14 )., (© 2022. The Author(s).)
- Published
- 2022
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5. IMI2-PainCare-BioPain-RCT3: a randomized, double-blind, placebo-controlled, crossover, multi-center trial in healthy subjects to investigate the effects of lacosamide, pregabalin, and tapentadol on biomarkers of pain processing observed by electroencephalography (EEG).
- Author
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Mouraux A, Bloms-Funke P, Boesl I, Caspani O, Chapman SC, Di Stefano G, Finnerup NB, Garcia-Larrea L, Goetz M, Kostenko A, Pelz B, Pogatzki-Zahn E, Schubart K, Stouffs A, Truini A, Tracey I, Troconiz IF, Van Niel J, Vela JM, Vincent K, Vollert J, Wanigasekera V, Wittayer M, Phillips KG, and Treede RD
- Subjects
- Biomarkers, Cross-Over Studies, Double-Blind Method, Healthy Volunteers, Humans, Lacosamide, Pain Measurement, Pregabalin adverse effects, Tapentadol, Electroencephalography, Pain
- Abstract
Background: IMI2-PainCare-BioPain-RCT3 is one of four similarly designed clinical studies aiming at profiling a set of functional biomarkers of drug effects on the nociceptive system that could serve to accelerate the future development of analgesics, by providing a quantitative understanding between drug exposure and effects of the drug on nociceptive signal processing in human volunteers. IMI2-PainCare-BioPain-RCT3 will focus on biomarkers derived from non-invasive electroencephalographic (EEG) measures of brain activity., Methods: This is a multisite single-dose, double-blind, randomized, placebo-controlled, 4-period, 4-way crossover, pharmacodynamic (PD) and pharmacokinetic (PK) study in healthy subjects. Biomarkers derived from scalp EEG measurements (laser-evoked brain potentials [LEPs], pinprick-evoked brain potentials [PEPs], resting EEG) will be obtained before and three times after administration of three medications known to act on the nociceptive system (lacosamide, pregabalin, tapentadol) and placebo, given as a single oral dose in separate study periods. Medication effects will be assessed concurrently in a non-sensitized normal condition and a clinically relevant hyperalgesic condition (high-frequency electrical stimulation of the skin). Patient-reported outcomes will also be collected. A sequentially rejective multiple testing approach will be used with overall alpha error of the primary analysis split between LEP and PEP under tapentadol. Remaining treatment arm effects on LEP or PEP or effects on EEG are key secondary confirmatory analyses. Complex statistical analyses and PK-PD modeling are exploratory., Discussion: LEPs and PEPs are brain responses related to the selective activation of thermonociceptors and mechanonociceptors. Their amplitudes are dependent on the responsiveness of these nociceptors and the state of the pathways relaying nociceptive input at the level of the spinal cord and brain. The magnitude of resting EEG oscillations is sensitive to changes in brain network function, and some modulations of oscillation magnitude can relate to perceived pain intensity, variations in vigilance, and attentional states. These oscillations can also be affected by analgesic drugs acting on the central nervous system. For these reasons, IMI2-PainCare-BioPain-RCT3 hypothesizes that EEG-derived measures can serve as biomarkers of target engagement of analgesic drugs for future Phase 1 clinical trials. Phase 2 and 3 clinical trials could also benefit from these tools for patient stratification., Trial Registration: This trial was registered 25/06/2019 in EudraCT ( 2019%2D%2D001204-37 ).
- Published
- 2021
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6. Pain behavior without pain sensation: an epileptic syndrome of "symbolism for pain"?
- Author
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Hagiwara K, Garcia-Larrea L, Tremblay L, Montavont A, Catenoix H, Rheims S, Guénot M, and Isnard J
- Subjects
- Adult, Electroencephalography methods, Female, Humans, Male, Pain etiology, Pain physiopathology, Seizures complications, Seizures physiopathology, Symbolism, Syndrome, Young Adult, Pain diagnosis, Pain Measurement methods, Pain Perception physiology, Seizures diagnosis, Stereotaxic Techniques
- Abstract
"Asymbolia for pain" has shown the potentiality of diseased insular networks to dissociate sensory from affective-behavioral dimensions of pain, resulting in the lack of appropriate motor and affective responses despite preserved sensory aspect of pain. Here, we describe 4 patients with an inverse phenomenon of asymbolia for pain, namely an isolated "symbolism for pain" triggered by epileptic seizures, characterized by pain behavior without declarative pain sensation despite fully preserved contact and vigilance. Stereoelectroencephalography demonstrated in each case focal seizure discharges within the posterior insulo-opercular cortex, with little or no propagation to other cortical structures, especially those considered to drive subjective pain experiences. The pain behavior might reflect seizure propagation from the insula to brain networks serving for behavioral responses associated with pain, including the cingulate motor region and possibly also the basal ganglia. We propose that the isolated symbolism for pain is a novel epileptic syndrome of dissociation between pain perception and behaviors associated with the insular nociceptive-related networks.
- Published
- 2020
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7. Hyperalgesia when observing pain-related images is a genuine bias in perception and enhances autonomic responses.
- Author
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Chapon A, Perchet C, Garcia-Larrea L, and Frot M
- Subjects
- Adolescent, Adult, Female, Humans, Hyperalgesia physiopathology, Male, Pain physiopathology, Photic Stimulation, Young Adult, Arousal physiology, Autonomic Nervous System physiopathology, Hyperalgesia psychology, Pain psychology, Pain Perception physiology
- Abstract
Observing pain in others can enhance our own pain. Two aspects of this effect remain unknown or controversial: first, whether it depends on the 'painfulness' of the visual stimulus; second, whether it reflects a genuine bias in perception or rather a bias in the memory encoding of the percept. Pain ratings and vegetative skin responses were recorded while 21 healthy volunteers received electric nociceptive shocks under three experimental conditions: (i) observing a painful contact between the body and a harmful object; (ii) observing a non-painful body contact, (iii) observing a control scene where the body and the object are not in contact. Pain reports and vegetative responses were enhanced exclusively when the subjects observed a painful body contact. The effect on perception was immediate, abated 3 sec after the shock, and positively correlated with the magnitude of vegetative arousal. This suggests that (a) hyperalgesia during observation of painful scenes was induced by their pain-related nature, and not by the simple body contact, and (b) hyperalgesia emerged from a very rapid bias in the perceptual encoding of the stimulus, and was not the result of a retrospective bias in memory recollection. Observing pain-depicting scenes can modify the processing of concomitant somatic stimuli, increasing their arousal value and shifting perception toward more painful levels.
- Published
- 2019
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8. Pain and consciousness.
- Author
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Garcia-Larrea L and Bastuji H
- Subjects
- Humans, Consciousness physiology, Pain physiopathology, Pain psychology
- Abstract
The aversive experience we call "pain" results from the coordinated activation of multiple brain areas, commonly described as a "pain matrix". This is not a fixed arrangement of structures but rather a fluid system composed of several interacting networks: A 'nociceptive matrix' includes regions receiving input from ascending nociceptive systems, and ensures the bodily characteristics of physical pain. A further set of structures receiving secondary input supports the 'salience' attributes of noxious stimuli, triggers top-down cognitive controls, and -most importantly- ensures the passage from pre-conscious nociception to conscious pain. Expectations and beliefs can still modulate the conscious experience via activity in supramodal regions with widespread cortical projections such as the ventral tegmental area. Intracortical EEG responses in humans show that nociceptive cortical processing is initiated in parallel in sensory, motor and limbic areas; it progresses rapidly to the recruitment of anterior insular and fronto-parietal networks, and finally to the activation of perigenual, posterior cingulate and hippocampal structures. Functional connectivity between sensory and high-level networks increases during the first second post-stimulus, which may be determinant for access to consciousness. A model is described, progressing from unconscious sensori-motor and limbic processing of spinothalamic and spino-parabrachial input, to an immediate sense of awareness supported by coordinated activity in sensorimotor and fronto-parieto-insular networks, and leading to full declarative consciousness through integration with autobiographical memories and self-awareness, involving posterior cingulate and medial temporal areas. This complete sequence is only present during full vigilance states. We contend, however, that even in unconscious subjects, repeated limbic and vegetative activation by painful stimuli via spino-amygdalar pathways can generate implicit memory traces and stimulus-response abnormal sequences, possibly contributing to long-standing anxiety or hyperalgesic syndromes in patients surviving coma., (Copyright © 2017 Elsevier Inc. All rights reserved.)
- Published
- 2018
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9. Convergence of sensory and limbic noxious input into the anterior insula and the emergence of pain from nociception.
- Author
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Bastuji H, Frot M, Perchet C, Hagiwara K, and Garcia-Larrea L
- Subjects
- Adult, Female, Humans, Male, Middle Aged, Amygdala physiopathology, Neural Pathways physiopathology, Nociception, Pain physiopathology, Synaptic Transmission
- Abstract
Two parallel di-synaptic routes convey nociceptive input to the telencephalon: the spino-thalamic system projecting principally to the posterior insula, and the spino-parabrachial pathway reaching the amygdalar nucleus. Interplay between the two systems underlies the sensory and emotional aspects of pain, and was explored here in humans with simultaneous recordings from the amygdala, posterior and anterior insulae. Onsets of thermo-nociceptive responses were virtually identical in the posterior insula and the amygdalar complex, but no significant functional connectivity was detected between them using coherence analysis. Anterior insular sectors responded with ~30 ms delay relative to both the posterior insula and the amygdala. While intra-insular functional correlation was significant during the whole analysis period, coherence between the anterior insula and the amygdala became significant after 700 ms of processing. Phase lags indicated information transfer initially directed from the amygdalar complex to the insula. Parallel but independent activation of sensory and limbic nociceptive networks appear to converge in the anterior insula in less than one second. While the anterior insula is often considered as providing input into the limbic system, our results underscore its reverse role, i.e., receiving and integrating very rapidly limbic with sensory input, to initiate a perceptual decision on the stimulus 'painfulness'.
- Published
- 2018
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10. Pain dilates time perception.
- Author
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Rey AE, Michael GA, Dondas C, Thar M, Garcia-Larrea L, and Mazza S
- Subjects
- Adult, Female, Humans, Male, Task Performance and Analysis, Time Factors, Pain physiopathology, Time Perception
- Abstract
We have all experienced that time seems stretched during unpleasant situations. While there is evidence of subjective time overestimation when perceiving external unpleasant stimuli, no study has measured the dilation of time when individuals experience an unpleasant situation in their own body. Here we measured the time dilation induced by a painful homeostatic deviance using temporal bisection task. We show that being in pain leads to an expansion of subjective time whereby a stronger increase in pain perception relative to non-painful stimulation leads to a stronger time-estimate distortion. Neurophysiological studies suggest that time estimation and the perception of self might share a common neural substrate. We propose that, along with bodily arousal and attentional capture, the enhancement of self-awareness may be critical to support dilated subjective time when experiencing pain. As other homeostatic deviances, pain may induce a focus on ourselves contributing to the impression that "time stands still".
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- 2017
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11. Thalamic pain: anatomical and physiological indices of prediction.
- Author
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Vartiainen N, Perchet C, Magnin M, Creac'h C, Convers P, Nighoghossian N, Mauguière F, Peyron R, and Garcia-Larrea L
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- Adult, Aged, Female, Humans, Male, Middle Aged, Predictive Value of Tests, Pain diagnosis, Pain etiology, Pain Measurement methods, Stroke complications, Stroke diagnosis, Thalamus anatomy & histology, Thalamus physiology
- Abstract
Thalamic pain is a severe and treatment-resistant type of central pain that may develop after thalamic stroke. Lesions within the ventrocaudal regions of the thalamus carry the highest risk to develop pain, but its emergence in individual patients remains impossible to predict. Because damage to the spino-thalamo-cortical system is a crucial factor in the development of central pain, in this study we combined detailed anatomical atlas-based mapping of thalamic lesions and assessment of spinothalamic integrity using quantitative sensory analysis and laser-evoked potentials in 42 thalamic stroke patients, of whom 31 had developed thalamic pain. More than 97% of lesions involved an area between 2 and 7 mm above the anterior-posterior commissural plane. Although most thalamic lesions affected several nuclei, patients with central pain showed maximal lesion convergence on the anterior pulvinar nucleus (a major spinothalamic target) while the convergence area lay within the ventral posterior lateral nucleus in pain-free patients. Both involvement of the anterior pulvinar nucleus and spinothalamic dysfunction (nociceptive thresholds, laser-evoked potentials) were significantly associated with the development of thalamic pain, whereas involvement of ventral posterior lateral nucleus and lemniscal dysfunction (position sense, graphaesthesia, pallaesthesia, stereognosis, standard somatosensory potentials) were similarly distributed in patients with or without pain. A logistic regression model combining spinothalamic dysfunction and anterior pulvinar nucleus involvement as regressors had 93% sensitivity and 87% positive predictive value for thalamic pain. Lesion of spinothalamic afferents to the posterior thalamus appears therefore determinant to the development of central pain after thalamic stroke. Sorting out of patients at different risks of developing thalamic pain may be achievable at the individual level by combining lesion localization and functional investigation of the spinothalamic system. As the methods proposed here do not need complex manipulations, they can be added to routine patients' work up, and the results replicated by other investigators in the field., (© The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
- Published
- 2016
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12. On the origin of painful somatosensory seizures.
- Author
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Montavont A, Mauguière F, Mazzola L, Garcia-Larrea L, Catenoix H, Ryvlin P, and Isnard J
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- Adult, Aged, Electroencephalography, Female, Humans, Male, Middle Aged, Pain Management, Seizures physiopathology, Seizures surgery, Somatosensory Cortex physiopathology, Somatosensory Cortex surgery, Video Recording, Cerebral Cortex physiopathology, Cerebral Cortex surgery, Pain etiology, Pain physiopathology, Seizures complications, Seizures therapy
- Abstract
Objective: To explore whether painful somatosensory seizures (PSS) are generated in the primary somatosensory cortex (SI area) or in the operculo-insular cortex., Methods: We analyzed ictal recordings and data from stimulation using intracerebral electrodes exploring the operculo-insular cortex (including secondary somatosensory [SII] region), SI area,and other areas of the pain matrix (cingulate gyrus and supplementary motor area) in a case series study of 5 patients with PSS., Results: Clinical features of PSS were different from those of seizures arising from the SI area: (1)pain intensity was higher; (2) pain spreading was not from one somatotopic territory to adjacentones; and (3) the spatial extent of pain was large, fitting better with the size of somatosensory receptive fields of the insula and SII region than of the SI area. The insula and SII region were systematically involved at the onset of seizures, rapidly followed by the opercular portion of SI area.The upper part of SI cortex was involved at a lesser degree, with some delay, and pain duration did not correlate in time with that of the discharge in SI. Ictal pain was consistently reproduced by stimulation of the insula or SII region but never by stimulating the SI area., Conclusions: These data strongly suggest that PSS originate in the operculo-insular cortex and not in the SI area and corroborate the concept that this region is involved in the sensory discriminative processing of pain inputs. Pain at the onset of PSS has a high value for localizing the epileptogenic area.
- Published
- 2015
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13. Filtering the reality: functional dissociation of lateral and medial pain systems during sleep in humans.
- Author
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Bastuji H, Mazza S, Perchet C, Frot M, Mauguière F, Magnin M, and Garcia-Larrea L
- Subjects
- Adolescent, Adult, Electrodes, Implanted, Electroencephalography, Evoked Potentials, Female, Humans, Male, Middle Aged, Young Adult, Brain physiology, Pain, Sleep physiology
- Abstract
Behavioral reactions to sensory stimuli during sleep are scarce despite preservation of sizeable cortical responses. To further understand such dissociation, we recorded intracortical field potentials to painful laser pulses in humans during waking and all-night sleep. Recordings were obtained from the three cortical structures receiving 95% of the spinothalamic cortical input in primates, namely the parietal operculum, posterior insula, and mid-anterior cingulate cortex. The dynamics of responses during sleep differed among cortical sites. In sleep Stage 2, evoked potential amplitudes were similarly attenuated relative to waking in all three cortical regions. During paradoxical, or rapid eye movements (REM), sleep, opercular and insular potentials remained stable in comparison with Stage 2, whereas the responses from mid-anterior cingulate abated drastically, and decreasing below background noise in half of the subjects. Thus, while the lateral operculo-insular system subserving sensory analysis of somatic stimuli remained active during paradoxical-REM sleep, mid-anterior cingulate processes related to orienting and avoidance behavior were suppressed. Dissociation between sensory and orienting-motor networks might explain why nociceptive stimuli can be either neglected or incorporated into dreams without awakening the subject., (Copyright © 2011 Wiley Periodicals, Inc.)
- Published
- 2012
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14. Insights gained into pain processing from patients with focal brain lesions.
- Author
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Garcia-Larrea L
- Subjects
- Animals, Humans, Pain Perception, Somatosensory Cortex physiopathology, Stroke physiopathology, Thalamic Diseases physiopathology, Thalamus physiopathology, Brain Injuries physiopathology, Cerebral Cortex physiopathology, Pain physiopathology, Spinothalamic Tracts physiopathology
- Abstract
The recognition that dissociated sensory loss affecting selectively pain and temperature results from lesions of the operculo-insular cortex is due to Biemond in 1956. This contrasted with the prevailing view that the sensory aspects of pain did not imply regions above the thalamus. Anatomical data in non-human primates, as well as electrophysiology and functional imaging in humans have now abundantly demonstrated that the opercular-insular region is the main cortical target of the spinothalamic system, and a vast number of reports have confirmed the relation between lesions in this region and the development of dissociated sensory symptoms and central neuropathic pain. Operculo-insular pain (parasylvian pain) is a distinct entity that can be clinically suspected and objectively diagnosed with combined radiological and electrophysiological methods, in particular evoked potentials to spinothalamic (laser) input. The region comprising the posterior insula and medial operculum may deserve being considered as a third somatosensory cortex (S3) contributing to the spinothalamic attributes of somatic perception., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2012
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15. Do we activate specifically somatosensory thin fibres with the concentric planar electrode? A scalp and intracranial EEG study.
- Author
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Perchet C, Frot M, Charmarty A, Flores C, Mazza S, Magnin M, and Garcia-Larrea L
- Subjects
- Electrodes statistics & numerical data, Electrodes, Implanted statistics & numerical data, Electroencephalography instrumentation, Electroencephalography standards, Female, Humans, Lasers, Solid-State, Male, Middle Aged, Pain diagnosis, Scalp innervation, Somatosensory Cortex cytology, Spinothalamic Tracts cytology, Young Adult, Electroencephalography methods, Evoked Potentials, Somatosensory physiology, Nerve Fibers, Myelinated physiology, Pain physiopathology, Somatosensory Cortex physiology, Spinothalamic Tracts physiology
- Abstract
Laser-evoked potentials (LEPs) are acknowledged as the most reliable laboratory tool for assessing thermal and pain pathways. Electrical stimulation with a newly developed planar concentric electrode, delivering stimuli limited to the superficial skin layers, has been suggested to provide selective activation of Aδ fibres without the inconveniences linked to laser stimulation. The aim of our study was to compare the scalp and intracranial responses to planar concentric electrode stimulation (CE-SEPs) with those of LEPs and standard somatosensory-evoked potentials (SEPs). Sixteen healthy subjects, 6 patients with intracortical electrodes, and 2 patients with selective lesions of the spinothalamic pathway were submitted to Neodymium:Yttrium-Aluminium-Perovskite laser stimulations, and electrical stimulations using standard electrodes or planar concentric electrodes (CE). In both healthy controls and epileptic implanted patients, CE- and standard SEPs showed significantly shorter latencies than LEPs. This is consistent with Aβ-fibre activation, peripheral activation time being unable to account for longer LEP latencies. In the patients with spinothalamic lesions, LEPs were absent after stimulation of the affected territory, while CE-SEPs were still present. For these 2 reasons, we conclude that the planar CE does not selectively activate the Aδ and C fibers, but coexcites a significant proportion of large myelinated Aβ fibres that dominate the ensuing cortical response. The use of CE-SEPs for the detection of spinothalamic system lesions is therefore not warranted; the planar electrode can, however, represent a useful tool to study nociceptive reflexes, which can be reliably elicited even in the presence of Aβ coactivation., (Copyright © 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.)
- Published
- 2012
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16. Does the insula tell our brain that we are in pain?
- Author
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Isnard J, Magnin M, Jung J, Mauguière F, and Garcia-Larrea L
- Subjects
- Electric Stimulation methods, Electrocoagulation adverse effects, Electroencephalography methods, Epilepsy etiology, Epilepsy pathology, Evoked Potentials physiology, Humans, Magnetic Resonance Imaging, Male, Time Factors, Young Adult, Brain Mapping, Cerebral Cortex physiopathology, Epilepsy complications, Pain complications, Pain pathology
- Abstract
Current knowledge on pain-related cerebral networks has relied so far on stimulus-induced brain responses, but not on the analysis of brain activity during spontaneous pain attacks. In this case report, correlation between intracerebral field potentials and online sensations during spontaneously painful epileptic seizures suggests a crucial role of the insula in the development of subjective pain. Attacks originated from a very limited dysplasia located in the posterior third of the right insula and propagated to other areas of the pain matrix, including the parietal operculum and the midcingulate gyrus. Concomitant painful symptoms started on the left hand or the left foot and extended in a few seconds to the whole left side of the body, sparing the head. Continuous during the first seconds of the attack, the painful feeling evolved to throbbing and remained so until it progressively vanished, together with the spike discharge. Stimulation of the insula, but not of other pain matrix regions, induced pain identical to that of seizures. After thermocoagulation of the insular epileptic focus, a short, transient exacerbation of seizures with same painful features but different location was observed before a long-lasting and complete remission of the attacks. Although these preliminary data need to be confirmed, they strongly suggest that if the full pain experience involves the pain matrix network, the posterior insula seems to play a leading role in the triggering of this network and the resulting emergence of subjective pain experience., (Copyright © 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.)
- Published
- 2011
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17. Operculo-insular pain (parasylvian pain): a distinct central pain syndrome.
- Author
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Garcia-Larrea L, Perchet C, Creac'h C, Convers P, Peyron R, Laurent B, Mauguière F, and Magnin M
- Subjects
- Adult, Afferent Pathways pathology, Afferent Pathways physiopathology, Electroencephalography methods, Female, Functional Laterality, Humans, Magnetic Resonance Imaging methods, Male, Middle Aged, Pain physiopathology, Pain Measurement methods, Physical Stimulation methods, Sensory Thresholds physiology, Thermosensing physiology, Brain Mapping, Cerebral Cortex pathology, Cerebral Cortex physiopathology, Evoked Potentials, Somatosensory physiology, Pain pathology, Touch physiology
- Abstract
Central pain with dissociated thermoalgesic sensory loss is common in spinal and brainstem syndromes but not in cortical lesions. Out of a series of 270 patients investigated because of somatosensory abnormalities, we identified five subjects presenting with central pain and pure thermoalgesic sensory loss contralateral to cortical stroke. All of the patients had involvement of the posterior insula and inner parietal operculum. Lemniscal sensory modalities (position sense, graphaestesia, stereognosis) and somatosensory evoked potentials to non-noxious inputs were always preserved, while thermal and pain sensations were profoundly altered, and laser-evoked potentials to thermo-nocoiceptive stimuli were always abnormal. Central pain resulting from posterior parasylvian lesions appears to be a distinct entity that can be identified unambiguously on the basis of clinical, radiological and electrophysiological data. It presents with predominant or isolated deficits for pain and temperature sensations, and is paradoxically closer to pain syndromes from brainstem lesions affecting selectively the spinothalamic pathways than to those caused by focal lesions of the posterior thalamus. The term 'pseudo-thalamic' is therefore inappropriate to describe it, and we propose parasylvian or operculo-insular pain as appropriate labels. Parasylvian pain may be extremely difficult to treat; the magnitude of pain-temperature sensory disturbances may be prognostic for its development, hence the importance of early sensory assessment with quantitative methods.
- Published
- 2010
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18. Involuntary orienting of attention to nociceptive events: neural and behavioral signatures.
- Author
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Legrain V, Perchet C, and García-Larrea L
- Subjects
- Adult, Analysis of Variance, Cognition physiology, Electroencephalography, Evoked Potentials, Female, Hand, Humans, Lasers, Male, Neuropsychological Tests, Reaction Time, Time Factors, Attention physiology, Brain physiopathology, Pain physiopathology
- Abstract
Pain can involuntarily capture attention and disrupt pain-unrelated cognitive activities. The brain mechanisms of these effects were explored by laser- and visual-evoked potentials. Consecutive nociceptive laser stimuli and visual stimuli were delivered in pairs. Subjects were instructed to ignore nociceptive stimuli while performing a task on visual targets. Because involuntary attention is particularly sensitive to novelty, in some trials (17%), unexpected laser stimuli were delivered on a different hand area (location-deviant) relative to the more frequent standard laser stimuli. Compared with frequent standard laser stimuli, deviant stimuli enhanced all nociceptive-evoked brain potentials (laser N1, N2, P2a, P2b). Deviant laser stimuli also decreased the amplitude of late latency-evoked responses (visual N2-P3) to the subsequent visual targets and delayed reaction times to them. The data confirm that nociceptive processing competes with pain-unrelated cognitive activities for attentional resources and that concomitant nociceptive events affect behavior by depressing attention allocation to ongoing cognitive processing. The laser-evoked potential magnitude reflected the engagement of attention to the novel nociceptive stimuli. We conclude that the laser-evoked potentials index the activity of a neural system involved in the detection of novel salient stimuli in order to focus attention and prioritize action to potentially damaging dangers.
- Published
- 2009
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19. Evoked potentials to nociceptive stimuli delivered by CO2 or Nd:YAP lasers.
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Perchet C, Godinho F, Mazza S, Frot M, Legrain V, Magnin M, and Garcia-Larrea L
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- Adult, Brain Mapping, Electroencephalography, Electromyography, Female, Functional Laterality, Humans, Male, Middle Aged, Reaction Time physiology, Evoked Potentials, Somatosensory physiology, Lasers, Gas adverse effects, Pain etiology, Pain Threshold physiology
- Abstract
Objective: This study compares the amplitude, latency, morphology, scalp topography and intracranial generators of laser-evoked potentials (LEPs) to CO(2) and Nd:YAP laser stimuli., Methods: LEPs were assessed in 11 healthy subjects (6 men, mean age 39+/-10 years) using a 32-channel acquisition system. Laser stimuli were delivered on the dorsum of both hands (intensity slightly above pain threshold), and permitted to obtain lateralised (N1) and vertex components (N2-P2) with similar scalp distribution for both types of lasers., Results: The N1-YAP had similar latencies but significantly higher amplitudes relative to N1-CO(2). The N2-P2 complex showed earlier latencies, higher amplitudes (N2) and more synchronised responses when using Nd:YAP stimulation. The distribution of intracranial generators assessed with source localization analyses (sLORETA) was similar for Nd:YAP and CO(2) lasers. The insular, opercular, and primary sensorimotor cortices were active during the N1 time-window, whereas the anterior midcingulate, supplementary motor areas and mid-anterior insulae were active concomitant to the N2-P2 complex., Conclusions: Earlier latencies and larger amplitudes recorded when using Nd:YAP pulses suggest a more synchronized nociceptive afferent volley with this type of laser., Significance: This, together with its handy utilization due to optic fibre transmission, may favour the use of Nd:YAP lasers in clinical settings.
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- 2008
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20. Pain influences hedonic assessment of visual inputs.
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Godinho F, Frot M, Perchet C, Magnin M, and Garcia-Larrea L
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- Adult, Evoked Potentials, Visual physiology, Female, Humans, Male, Brain physiology, Brain Mapping, Emotions physiology, Pain physiopathology, Visual Perception physiology
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It is acknowledged that the emotional state created by visual inputs can modulate the way we feel pain; however, little is known about how acute pain influences the emotional assessment of what we see. In this study healthy subjects scored affective images while receiving painful or innocuous electrical shocks. Painful stimuli did not make unpleasant images more unpleasant, but rendered pleasant pictures significantly less pleasant. Brain responses to visual inputs (64-channels electroencephalogram) mirrored behavioural results, showing pain-induced effects in the orbitofrontal cortex, the subgenual portion of the cingulate gyrus, the anterior prefrontal and the temporal cortices, exclusively during presentation of pleasant images. In addition to this specific effect on pleasant pictures, pain also produced non-specific effects upon all categories of images, engaging cerebral areas associated with attention, alertness and motor preparation (middle-cingulate, supplemental motor, prefrontal cortex). Thus, pain appears to have a dual influence on visual processing: a non-specific effect related to orienting phenomena; and a more specific action exerted on supra-modal limbic areas involved in the production of affective states. The latter correlated with changes in the subjective appraisal of visual stimuli, and may underlie not only the change in their subjective assessment but also reactive processes aimed at coping with unpleasant contexts.
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- 2008
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21. Parallel processing of nociceptive A-delta inputs in SII and midcingulate cortex in humans.
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Frot M, Mauguière F, Magnin M, and Garcia-Larrea L
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- Adolescent, Adult, Brain Mapping methods, Female, Humans, Male, Middle Aged, Pain Measurement methods, Reaction Time physiology, Time Factors, Gyrus Cinguli physiology, Nociceptors physiology, Pain physiopathology, Somatosensory Cortex physiology
- Abstract
The cingulate cortex (CC) as a part of the "medial" pain subsystem is generally assumed to be involved in the affective and/or cognitive dimensions of pain processing, which are viewed as relatively slow processes compared with the sensory-discriminative pain coding by the lateral second somatosensory area (SII)-insular cortex. The present study aimed at characterizing the location and timing of the CC evoked responses during the 1 s period after a painful laser stimulus, by exploring the whole rostrocaudal extent of this cortical area using intracortical recordings in humans. Only a restricted area in the median CC region responded to painful stimulation, namely the posterior midcingulate cortex (pMCC), the location of which is consistent with the so-called "motor CC" in monkeys. Cingulate pain responses showed two components, of which the earliest peaked at latencies similar to those obtained in SII. These data provide direct evidence that activations underlying the processing of nociceptive information can occur simultaneously in the "medial" and "lateral" subsystems. The existence of short-latency pMCC responses to pain further indicates that the "medial pain system" is not devoted exclusively to the processing of emotional information, but is also involved in fast attentional orienting and motor withdrawal responses to pain inputs. These functions are, not surprisingly, conducted in parallel with pain intensity coding and stimulus localization specifically subserved by the sensory-discriminative "lateral" pain system.
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- 2008
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22. Motor cortex stimulation for neuropathic pain: From phenomenology to mechanisms.
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Garcia-Larrea L and Peyron R
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- Animals, Cerebrovascular Circulation physiology, Chronic Disease, Endorphins metabolism, Humans, Magnetic Resonance Imaging, Neurosurgical Procedures, Pain diagnostic imaging, Peripheral Nervous System Diseases diagnostic imaging, Positron-Emission Tomography, Motor Cortex physiology, Pain etiology, Pain Management, Peripheral Nervous System Diseases complications, Peripheral Nervous System Diseases therapy
- Abstract
Motor cortex stimulation (MCS) is relatively recent neurosurgical technique for pain control, the use of which is growing steadily since its description in the last decade. While clinical series show that at least 50% of patients with chronic, pharmacoresistant neuropathic pain may benefit from this technique, the mechanisms of action of MCS remain elusive. In this review, we synthesise a number of studies that, combining electrophysiology and functional imaging, have permitted to proceed from phenomenology to models that may account for part of such mechanisms. MCS appears to trigger rapid and phasic activation in the lateral thalamus, which leads to a cascade of events of longer time-course in medial thalamus, anterior cingulate/orbitofrontal cortices and periaqueductal grey matter. Activity in these latter structures is delayed relative to actual cortical neurostimulation and becomes maximal during the hours that follow MCS arrest. Current hypotheses suggest that MCS may act through at least two mechanisms: activation of perigenual cingulate and orbitofrontal areas may modulate the emotional appraisal of pain, rather than its intensity, while top down activation of brainstem PAG may lead to descending inhibition toward the spinal cord. Recent evidence also points to a possible secretion of endogenous opioids triggered by chronic MCS. This, along with the delayed and long-lasting activation of several brain structures, is consistent with the clinical effects of MCS, which may also last for hours or days after MCS discontinuation.
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- 2007
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23. Emotional modulation of pain: is it the sensation or what we recall?
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Godinho F, Magnin M, Frot M, Perchet C, and Garcia-Larrea L
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- Adult, Electric Stimulation methods, Female, Humans, Male, Pain psychology, Photic Stimulation methods, Emotions physiology, Mental Recall physiology, Pain physiopathology, Pain Measurement methods, Sensation physiology
- Abstract
Emotions modulate pain perception, although the mechanisms underlying this phenomenon remain unclear. In this study, we show that intensity reports significantly increased when painful stimuli were concomitant to images showing human pain, whereas pictures with identical emotional values but without somatic content failed to modulate pain. Early somatosensory responses (<200 ms) remained unmodified by emotions. Conversely, late responses showed a significant enhancement associated with increased pain ratings, localized to the right prefrontal, right temporo-occipital junction, and right temporal pole. In contrast to selective attention, which enhances pain ratings by increasing sensory gain, emotions triggered by seeing other people's pain did not alter processing in SI-SII (primary and second somatosensory areas), but may have biased the transfer to, and the representation of pain in short-term memory buffers (prefrontal), as well as the affective assignment to this representation (temporal pole). Memory encoding and recall, rather than sensory processing, appear to be modulated by empathy with others' physical suffering.
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- 2006
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24. Cognitive modulation of pain-related brain responses. Comments on Seminowicz et al. (Pain 2004;112:48-58).
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Legrain V, Plaghki L, and García-Larrea L
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- Humans, Attention physiology, Cognition physiology, Pain physiopathology, Pain psychology
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- 2005
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25. Thalamic thermo-algesic transmission: ventral posterior (VP) complex versus VMpo in the light of a thalamic infarct with central pain.
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Montes C, Magnin M, Maarrawi J, Frot M, Convers P, Mauguière F, and Garcia-Larrea L
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- Brain Mapping, Electroencephalography methods, Evoked Potentials, Somatosensory physiology, Functional Laterality physiology, Humans, Hyperalgesia pathology, Hyperalgesia physiopathology, Imaging, Three-Dimensional methods, Magnetic Resonance Imaging methods, Male, Middle Aged, Neural Pathways physiopathology, Neuropsychological Tests statistics & numerical data, Pain physiopathology, Reaction Time, Thalamus physiopathology, Brain Infarction pathology, Neural Pathways pathology, Pain pathology, Thalamus pathology
- Abstract
The respective roles of the ventral posterior complex (VP) and of the more recently described VMpo (posterior part of the ventral medial nucleus) as thalamic relays for pain and temperature pathways have recently been the subject of controversy. Data we obtained in one patient after a limited left thalamic infarct bring some new insights into this debate. This patient presented sudden right-sided hypesthesia for both lemniscal (touch, vibration, joint position) and spinothalamic (pain and temperature) modalities. He subsequently developed right-sided central pain with allodynia. Projection of 3D magnetic resonance images onto a human thalamic atlas revealed a lesion involving the anterior two thirds of the ventral posterior lateral nucleus (VPL) and, to a lesser extent, the ventral posterior medial (VPM) and inferior (VPI) nuclei. Conversely, the lesion did not extend posterior and ventral enough to concern the putative location of the spinothalamic-afferented nucleus VMpo. Neurophysiological studies showed a marked reduction (67%) of cortical responses depending on dorsal column-lemniscal transmission, while spinothalamic-specific, CO2-laser induced cortical responses were only moderately attenuated (33%). Our results show that the VP is definitely involved in thermo-algesic transmission in man, and that its selective lesion can lead to central pain. However, results also suggest that much of the spino-thalamo-cortical volley elicited by painful heat stimuli does not transit through VP, supporting the hypothesis that a non-VP locus lying more posteriorly in the human thalamus is important for thermo-algesic transmission.
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- 2005
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26. Predictive value of somatosensory evoked potentials for long-lasting pain relief after spinal cord stimulation: practical use for patient selection.
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Sindou MP, Mertens P, Bendavid U, García-Larrea L, and Mauguière F
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- Adult, Aged, Chronic Disease, Electrodes, Implanted, Female, Follow-Up Studies, Humans, Male, Middle Aged, Neural Conduction physiology, Pain etiology, Pain Measurement, Predictive Value of Tests, Reaction Time physiology, Spinal Cord Diseases complications, Time Factors, Electric Stimulation Therapy, Evoked Potentials, Somatosensory physiology, Outcome Assessment, Health Care, Pain physiopathology, Pain Management, Patient Selection, Spinal Cord Diseases physiopathology, Spinal Cord Diseases therapy
- Abstract
Objective: Spinal cord stimulation (SCS) has been used for more than 30 years in patients with intractable neuropathic pain, and global success rates have varied from 40 to 70%, according to reported series. Patient selection is currently based on a preliminary percutaneous test, which is useful but invasive, increases the risk of infection, and has yielded false-positive and false-negative results. In this study, we evaluated an alternative method of predicting the effectiveness of SCS before deciding whether to implant laminotomy electrodes-specifically, assessment of neural conduction in the dorsal columns with the use of somatosensory evoked potentials (SSEPs). Thus, we examined the value of preoperative central conduction time (CCT) of SSEPs to stimulation at the level of the painful area as a possible predictor of patient outcome after SCS., Methods: Ninety-five patients were evaluated during a mean follow-up period of 18.8 months. Patients were classified into four categories according to the location of the lesion responsible for pain: 28 patients had lesions of the peripheral nerves, 27 had radicular lesions, 8 had root avulsions, and 32 had cord lesions. The SCS electrode was implanted through an interlaminar opening at the upper part of the painful territory without performing a percutaneous screening test. Clinical and social markers of pain relief (i.e., Visual Analog Scale scores, analgesic drug intake, work status) were evaluated prospectively 2 months after implantation and then annually., Results: The global success rate in our study group, with success defined as at least 50% long-term pain relief, was 54.7% (52 of 95 patients). Statistical analyses showed a clear influence of preoperative CCT on SCS outcome. Thus, the success rate was nil in patients with significantly abnormal CCT, whereas it was 75.4% in patients with normal preoperative SSEPs. Significant differences between the two groups of patients also were observed with regard to medication intake and work status., Conclusion: Preoperative SSEPs provide an objective prediction of patient outcome after SCS. We suggest that if a patient's CCT is abolished or significantly altered, the patient should not undergo SCS.
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- 2003
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27. Laser-evoked potential abnormalities in central pain patients: the influence of spontaneous and provoked pain.
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Garcia-Larrea L, Convers P, Magnin M, André-Obadia N, Peyron R, Laurent B, and Mauguière F
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- Adult, Aged, Analysis of Variance, Chi-Square Distribution, Female, Humans, Hyperalgesia diagnosis, Hyperalgesia physiopathology, Male, Middle Aged, Pain diagnosis, Evoked Potentials physiology, Lasers, Pain physiopathology
- Abstract
We recorded laser-evoked cortical potentials (LEPs) in 54 consecutive patients presenting with unilateral neuropathic central pain (n = 42) or with lateralized pain of non-organic origin (n = 12). A number of cases in each group had superimposed hyperalgesia or allodynia. In patients with central pain, LEPs were significantly attenuated after stimulation over the painful territory, relative to stimulation of the homologous normal territory. LEP attenuation concerned not only patients with decreased pain/heat sensation, but also those with allodynia or hyperalgesia to laser pulses. In contrast, LEPs were never attenuated in patients with non-organic forms of pain, in whom LEPs could even be enhanced to stimulation of the painful territory. Increased responses in non-organic pain were a reminder of the cognitive modulation observed in normal subjects who direct attention to a laser stimulus. Enhanced LEPs never accompanied truly neuropathic hyperalgesia or allodynia. In central pain patients with exclusively spontaneous pain, LEP attenuation was more pronounced than that observed in those with allodynia and hyperalgesia. Patients with allodynia also presented occasionally ultra-late responses (>700 ms) to stimulation of the painful side. The hypothesis that such responses may reflect activation of a slow conducting 'medial' pain system is discussed. We conclude that, as currently recorded, LEPs essentially reflect the activity of a 'lateral' pain system subserved at the periphery by rapidly conducting A-delta fibres. They are useful to document the sensorial deficits (deafferentation) leading to neuropathic pain syndromes. Conversely, in the case of deafferentation, they fail to index adequately the affective aspects of pain sensation. On practical grounds, chronic pain coupled with reduced LEPs substantiates the diagnosis of neuropathic pain, whereas the finding of normal or enhanced LEPs to stimulation of a painful territory suggests the integrity of pain pathways, and does not support a neuropathic pathophysiology. In neuropathic cases, partial LEP preservation might increase the probability of developing provoked pain (allodynia/hyperalgesia). The possible predictive value of this phenomenon, when observed before the development of pain, remains to be demonstrated. In selected contexts (pain sine materia, non-organic anaesthesia), normal or enhanced LEPs may support a psychogenic participation in the syndrome.
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- 2002
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28. On insular responses and laser-evoked potentials.
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Garcia-Larrea L
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- Evoked Potentials physiology, Humans, Cerebral Cortex physiology, Lasers, Pain physiopathology
- Published
- 2002
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29. Fractal Similarity of Pain Brain Networks
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Fauchon, Camille, Bastuji, Hélène, Peyron, Roland, Garcia-Larrea, Luis, Schousboe, Arne, Series Editor, and Di Ieva, Antonio, editor
- Published
- 2024
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30. Non-invasive cortical stimulation for drugresistant pain.
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Garcia-Larrea, Luis
- Abstract
Purpose of review Neuromodulation techniques are being increasingly used to alleviate pain and enhance quality of life. Noninvasive cortical stimulation was originally intended to predict the efficacy of invasive (neurosurgical) techniques, but has now gained a place as an analgesic procedure in its own right. Recent findings Repetitive transcranial magnetic stimulation (rTMS): Evidence from 14 randomised, placebo-controlled trials (~750 patients) supports a significant analgesic effect of high-frequency motor cortex rTMS in neuropathic pain. Dorsolateral frontal stimulation has not proven efficacious so far. The posterior operculo-insular cortex is an attractive target but evidence remains insufficient. Short-term efficacy can be achieved with NNT (numbers needed to treat) ~2-3, but long-lasting efficacy remains a challenge. Like rTMS, transcranial direct-current stimulation (tDCS) induces activity changes in distributed brain networks and can influence various aspects of pain. Lower cost relative to rTMS, few safety issues and availability of home-based protocols are practical advantages. The limited quality of many published reports lowers the level of evidence, which will remain uncertain until more prospective controlled studies are available. Summary Both rTMS and tDCS act preferentially upon abnormal hyperexcitable states of pain, rather than acute or experimental pain. For both techniques, M1 appears to be the best target for chronic pain relief, and repeated sessions over relatively long periods of time may be required to obtain clinically significant benefits. Patients responsive to tDCS may differ from those improved by rTMS. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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31. Pharmacological Probes to Validate Biomarkers for Analgesic Drug Development.
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van Niel, Johannes, Bloms-Funke, Petra, Caspani, Ombretta, Cendros, Jose Maria, Garcia-Larrea, Luis, Truini, Andrea, Tracey, Irene, Chapman, Sonya C., Marco-Ariño, Nicolás, Troconiz, Iñaki F., Phillips, Keith, Finnerup, Nanna Brix, Mouraux, André, and Treede, Rolf-Detlef
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DRUG development ,CLINICAL trials ,ANALGESICS ,BIOMARKERS ,CHRONIC pain ,CHRONIC diseases - Abstract
There is an urgent need for analgesics with improved efficacy, especially in neuropathic and other chronic pain conditions. Unfortunately, in recent decades, many candidate analgesics have failed in clinical phase II or III trials despite promising preclinical results. Translational assessment tools to verify engagement of pharmacological targets and actions on compartments of the nociceptive system are missing in both rodents and humans. Through the Innovative Medicines Initiative of the European Union and EFPIA, a consortium of researchers from academia and the pharmaceutical industry was established to identify and validate a set of functional biomarkers to assess drug-induced effects on nociceptive processing at peripheral, spinal and supraspinal levels using electrophysiological and functional neuroimaging techniques. Here, we report the results of a systematic literature search for pharmacological probes that allow for validation of these biomarkers. Of 26 candidate substances, only 7 met the inclusion criteria: evidence for nociceptive system modulation, tolerability, availability in oral form for human use and absence of active metabolites. Based on pharmacokinetic characteristics, three were selected for a set of crossover studies in rodents and healthy humans. All currently available probes act on more than one compartment of the nociceptive system. Once validated, biomarkers of nociceptive signal processing, combined with a pharmacometric modelling, will enable a more rational approach to selecting dose ranges and verifying target engagement. Combined with advances in classification of chronic pain conditions, these biomarkers are expected to accelerate analgesic drug development. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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32. Les fonctions sensorielles et la maladie d'Alzheimer : une approche multidisciplinaire
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Kenigsberg, Paul-Ariel, Aquino, Jean-Pierre, Berard, Alain, Boucart, Muriel, Bouccara, Didier, Brand, Gérard, Charras, Kevin, Garcia-Larrea, Luis, Gzil, Fabrice, Krolak-Salmon, Pierre, Madjlessi, Arach, Malaquin-Pavan, Evelyne, Pénicaud, Luc, Platel, Hervé, Pozzo, Thierry, Reintjens, Christophe, Salmon, Eric, Vergnon, Laurent, Robert, Philippe, Fondation Médéric Alzheimer, UMR 8160 Laboratoire de neurosciences fonctionnelles et pathologie, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Service ORL, CHU Pitié-Salpêtrière [APHP], Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Société Française de Réflexion Sensori-Cognitive (Sofresc), Hôpital Vaugirard-Gabriel Pallez, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Neuropsychologie cognitive et neuroanatomie fonctionnelles de la mémoire humaine, École pratique des hautes études (EPHE)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cognition, Action, et Plasticité Sensorimotrice [Dijon - U1093] (CAPS), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de neurologie, Centre de jour de la mémoire, Centre Hospitalier Universitaire de Liège, Groupement de recherche Alzheimer-presbyacousie (GRAP-santé), Centre Hospitalier Simone Veil (CH Simone Veil), Centre mémoire de ressources et de recherche, CoBTeK-IA, Centre Hospitalier Universitaire de Nice (CHU de Nice)-Université de Nice Sophia-Antipolis (UNSA), fondation médéric alzheimer, Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ) -Centre National de la Recherche Scientifique ( CNRS ), Centre des Sciences du Goût et de l'Alimentation [Dijon] ( CSGA ), Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS ), Centre de recherche en neurosciences de Lyon ( CRNL ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] ( UJM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Société Française de Réflexion Sensori-Cognitive ( Sofresc ), Hôpital gériatrique Vaugirard-Gabriel Pallez, Assistance Publique - Hôpitaux de Paris, Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -École pratique des hautes études ( EPHE ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Cognition, Action, et Plasticité Sensorimotrice [Dijon - U1093] ( CAPS ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Simone Veil ( CH Simone Veil ), Centre Hospitalier Universitaire de Nice ( CHU de Nice ) -Université de Nice - Sophia Antipolis ( UNSA ), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre National de la Recherche Scientifique (CNRS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-École pratique des hautes études (EPHE), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)
- Subjects
cognition ,vision ,maladie d'Alzheimer ,[ SDV.AEN ] Life Sciences [q-bio]/Food and Nutrition ,[SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology ,detection ,goût ,balance ,qualité de vie ,[ SDV.MHEP.GEG ] Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology ,Alzheimer's disease ,rehabilitation ,taste ,repérage ,quality of life ,hearing ,pain ,équilibre ,douleur ,[SDV.AEN]Life Sciences [q-bio]/Food and Nutrition ,olfaction - Abstract
Relations between sensory functions and Alzheimer's disease are still under explored.To understand them better, theFondation MédfJricAlzheimer has brought together a multi-disciplinary expert group. Aristote's five senses must be enhanced by today's know ledge of proprioception, motor cognition and pain perception. When cognition breaks dawn, the persan with dementia perceives the world around her with her sensory experience, yet is unable to intagratB all this information to understand the contaxt.The trBBtment of mul tiple sensory inputs by the brain is closely linked to cognitive processes. Sensory deficits reduce considerably the autonomy of people with dementia in their daily fife and their rela tions with others, increase their social isolation and the risk of accidents. Professionals involved with neurodegenerative diseases remain poorly aware of sensory deficits, which can bias the results of cognitive tests. However. there are simple tools to detect these deficits, notably for vision, hearing and balance disorders, which can be corrected. Many interventions for cognitive rehabilitation or quality of fife improvement are based on sen sory functions. The environment of people with dementia must be adapted to become understandable, comfortable, safe and eventually therapeutic.; Afin de mieux comprendre les relations, encore insuffisamment étudiées, entre les fonctions sensorielles et la maladie d'Alzheimer, la Fondation Médéric Alzheimer a réuni un groupe d'experts multi-disciplinaire. Aux cinq sens d'Aristote, il faut aujourd'hui ajouter la proprioception, la cognition motrice et la perception de la douleur. Lorsque la cognition se détériore, la personne atteinte de la maladie d'Alzheimer voit le monde qui l'entoure avec son expérience sensorielle, sans qu'elle puisse toutefois intégrer toutes ces informations pour comprendre le contexte. Le traitement des multiples informations sensorielles par le cerveau est étroitement lié à des processus cognitifs. Les déficits sensoriels réduisent considérablement l'autonomie des personnes malades dans la vie quotidienne, leurs relations avec autrui, augmentent leur isolement social et le risque d'accidents. Les professionnels impliqués dans les maladies neurodégénératives restent insuffisamment sensibilisés aux déficits sensoriels, qui peuvent fausser l'évaluation de la cognition. Il existe pourtant des outils de repérage simples de ces déficits, notamment pour les troubles de la vision, de l'audition et de l'équilibre qui peuvent être corrigés. De nombreuses interventions pour la réhabilitation cognitive ou l'amélioration de la qualité de vie s'appuient sur les fonctions sensorielles. L'environnement des personnes malades doit être adapté pour le rendre compréhensible, confortable, sûr et si possible thérapeutique.
- Published
- 2015
33. Evidence-based source modeling of nociceptive cortical responses: A direct comparison of scalp and intracranial activity in humans.
- Author
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Bradley, Claire, Bastuji, Hélène, and Garcia‐Larrea, Luis
- Abstract
Background Source modeling of EEG traditionally relies on interplay between physiological hypotheses and mathematical estimates. We propose to optimize the process by using evidence gathered from brain imaging and intracortical recordings. Methods We recorded laser-evoked potentials in 18 healthy participants, using high-density EEG. Brain sources were modeled during the first second poststimulus, constraining their initial position to regions where nociceptive-related activity has been ascertained by intracranial EEG. These comprised the two posterior operculo-insular regions, primary sensorimotor, posterior parietal, anterior cingulate/supplementary motor (ACC/SMA), bilateral frontal/anterior insular, and posterior cingulate (PCC) cortices. Results The model yielded an average goodness of fit of 91% for individual and 95.8% for grand-average data. When compared with intracranial recordings from 27 human subjects, no significant difference in peak latencies was observed between modeled and intracranial data for 5 of the 6 assessable regions. Morphological match was excellent for operculo-insular, frontal, ACC/SMA and PCC regions (cross-correlation > 0.7) and fair for sensori-motor and posterior parietal cortex (c-c ∼ 0.5). Conclusions Multiple overlapping activities evoked by nociceptive input can be disentangled from high-density scalp EEG guided by intracranial data. Modeled sources accurately described the timing and morphology of most activities recorded with intracranial electrodes, including those coinciding with the emergence of stimulus awareness. Hum Brain Mapp 38:6083-6095, 2017. © 2017 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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34. Parallel processing of nociceptive A-delta inputs in SII and midcingulate cortex in humans
- Author
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Frot, Maud, Mauguiere, François, Magnin, Michel, Garcia-Larrea, Luis, Mauguière, F., Intégration centrale de la douleur chez l'homme, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Neurologie Fonctionnelle et d'Epileptologie, Hospices Civils de Lyon (HCL), Frot, Maud, NeuroPain - CRNL, Centre de recherche en neurosciences de Lyon (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de neurologie fonctionnelle et d'épileptologie, Hospices Civils de Lyon (HCL)-Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL)-Université de Lyon, INSERM E342, Institut National de la Santé et de la Recherche Médicale (INSERM), The Neurodis Fondation, and Neurodis
- Subjects
Cingulate cortex ,Adult ,Male ,Time Factors ,Adolescent ,Painful Stimulation ,Pain ,MESH: Pain Measurement ,Stimulus (physiology) ,Somatosensory system ,Gyrus Cinguli ,Pain processing ,MESH: Somatosensory Cortex ,03 medical and health sciences ,0302 clinical medicine ,Midcingulate cortex ,MESH: Gyrus Cinguli ,Reaction Time ,Humans ,[SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,MESH: Nociceptors ,MESH: Brain Mapping ,030304 developmental biology ,Pain Measurement ,MESH: Adolescent ,0303 health sciences ,Brain Mapping ,MESH: Humans ,MESH: Middle Aged ,General Neuroscience ,MESH: Time Factors ,Nociceptors ,MESH: Adult ,Articles ,Somatosensory Cortex ,Middle Aged ,MESH: Male ,MESH: Reaction Time ,Pain responses ,Nociception ,Female ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,MESH: Pain ,Psychology ,Neuroscience ,MESH: Female ,030217 neurology & neurosurgery - Abstract
International audience; The cingulate cortex (CC) as a part of the "medial" pain subsystem is generally assumed to be involved in the affective and/or cognitive dimensions of pain processing, which are viewed as relatively slow processes compared with the sensory-discriminative pain coding by the lateral second somatosensory area (SII)-insular cortex. The present study aimed at characterizing the location and timing of the CC evoked responses during the 1 s period after a painful laser stimulus, by exploring the whole rostrocaudal extent of this cortical area using intracortical recordings in humans. Only a restricted area in the median CC region responded to painful stimulation, namely the posterior midcingulate cortex (pMCC), the location of which is consistent with the so-called "motor CC" in monkeys. Cingulate pain responses showed two components, of which the earliest peaked at latencies similar to those obtained in SII. These data provide direct evidence that activations underlying the processing of nociceptive information can occur simultaneously in the "medial" and "lateral" subsystems. The existence of short-latency pMCC responses to pain further indicates that the "medial pain system" is not devoted exclusively to the processing of emotional information, but is also involved in fast attentional orienting and motor withdrawal responses to pain inputs. These functions are, not surprisingly, conducted in parallel with pain intensity coding and stimulus localization specifically subserved by the sensory-discriminative "lateral" pain system.
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- 2008
35. Thalamic pain: anatomical and physiological indices of prediction.
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Vartiainen, Nuutti, Perchet, Caroline, Magnin, Michel, Creac'h, Christelle, Convers, Philippe, Nighoghossian, Norbert, Mauguière, François, Peyron, Roland, and Garcia-Larrea, Luis
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STROKE ,THALAMIC nuclei ,MEDICAL emergencies ,BRAIN mapping ,BRAIN anatomy ,NEUROLOGY ,PAIN diagnosis ,THALAMUS physiology ,THALAMUS ,STROKE diagnosis ,PAIN ,PAIN measurement ,PREDICTIVE tests ,DISEASE complications ,ANATOMY - Abstract
Thalamic pain is a severe and treatment-resistant type of central pain that may develop after thalamic stroke. Lesions within the ventrocaudal regions of the thalamus carry the highest risk to develop pain, but its emergence in individual patients remains impossible to predict. Because damage to the spino-thalamo-cortical system is a crucial factor in the development of central pain, in this study we combined detailed anatomical atlas-based mapping of thalamic lesions and assessment of spinothalamic integrity using quantitative sensory analysis and laser-evoked potentials in 42 thalamic stroke patients, of whom 31 had developed thalamic pain. More than 97% of lesions involved an area between 2 and 7 mm above the anterior-posterior commissural plane. Although most thalamic lesions affected several nuclei, patients with central pain showed maximal lesion convergence on the anterior pulvinar nucleus (a major spinothalamic target) while the convergence area lay within the ventral posterior lateral nucleus in pain-free patients. Both involvement of the anterior pulvinar nucleus and spinothalamic dysfunction (nociceptive thresholds, laser-evoked potentials) were significantly associated with the development of thalamic pain, whereas involvement of ventral posterior lateral nucleus and lemniscal dysfunction (position sense, graphaesthesia, pallaesthesia, stereognosis, standard somatosensory potentials) were similarly distributed in patients with or without pain. A logistic regression model combining spinothalamic dysfunction and anterior pulvinar nucleus involvement as regressors had 93% sensitivity and 87% positive predictive value for thalamic pain. Lesion of spinothalamic afferents to the posterior thalamus appears therefore determinant to the development of central pain after thalamic stroke. Sorting out of patients at different risks of developing thalamic pain may be achievable at the individual level by combining lesion localization and functional investigation of the spinothalamic system. As the methods proposed here do not need complex manipulations, they can be added to routine patients' work up, and the results replicated by other investigators in the field. [ABSTRACT FROM AUTHOR]
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- 2016
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36. Cortical representation of pain in primary sensory-motor areas (S1/M1)-a study using intracortical recordings in humans.
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Frot, Maud, Magnin, Michel, Mauguière, François, and Garcia‐Larrea, Luis
- Abstract
Intracortical evoked potentials to nonnoxious Aβ (electrical) and noxious Aδ (laser) stimuli within the human primary somatosensory (S1) and motor (M1) areas were recorded from 71 electrode sites in 9 epileptic patients. All cortical sites responding to specific noxious inputs also responded to nonnoxious stimuli, while the reverse was not always true. Evoked responses in S1 area 3b were systematic for nonnoxious inputs, but seen in only half of cases after nociceptive stimulation. Nociceptive responses were systematically recorded when electrode tracks reached the crown of the postcentral gyrus, consistent with an origin in somatosensory areas 1-2. Sites in the precentral cortex also exhibited noxious and nonnoxious responses with phase reversals indicating a local origin in area 4 (M1). We conclude that a representation of thermal nociceptive information does exist in human S1, although to a much lesser extent than the nonnociceptive one. Notably, area 3b, which responds massively to nonnoxious Aβ activation was less involved in the processing of noxious heat. S1 and M1 responses to noxious heat occurred at latencies comparable to those observed in the supra-sylvian opercular region of the same patients, suggesting a parallel, rather than hierarchical, processing of noxious inputs in S1, M1 and opercular cortex. This study provides the first direct evidence for a spinothalamic related input to the motor cortex in humans. Hum Brain Mapp 34:2655-2668, 2013. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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37. Parallel Processing of Nociceptive A-δInputs in SII and Midcingulate Cortex in Humans.
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Frot, Maud, Mauguière, François, Magnin, Michel, and Garcia-Larrea, Luis
- Subjects
PREFRONTAL cortex ,PAIN ,SENSORY neurons ,LABORATORY monkeys ,NEUROSCIENCES - Abstract
The cingulate cortex (CC) as a part of the "medial" pain subsystem is generally assumed to be involved in the affective and/or cognitive dimensions of pain processing, which are viewed as relatively slow processes compared with the sensory-discriminative pain coding by the lateral second somatosensory area (SII)-insular cortex. The present study aimed at characterizing the location and timing of the CC evoked responses during the 1 s period after a painful laser stimulus, by exploring the whole rostrocaudal extent of this cortical area using intracortical recordings in humans. Only a restricted area in the medianCCregion responded to painful stimulation, namely the posterior midcingulate cortex (pMCC), the location of which is consistent with the so-called "motor CC" in monkeys. Cingulate pain responses showed two components, of which the earliest peaked at latencies similar to those obtained in SII. These data provide direct evidence that activations underlying the processing of nociceptive information can occur simultaneously in the "medial" and "lateral" subsystems. The existence of short-latency pMCC responses to pain further indicates that the "medial pain system" is not devoted exclusively to the processing of emotional information, but is also involved in fast attentional orienting and motor withdrawal responses to pain inputs. These functions are, not surprisingly, conducted in parallel with pain intensity coding and stimulus localization specifically subserved by the sensory-discriminative "lateral" pain system. [ABSTRACT FROM AUTHOR]
- Published
- 2008
- Full Text
- View/download PDF
38. Modulation attentionnelle et cognitive des re´ponses e´voque´es par laser
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Lorenz, Jürgen and Garcia-Larrea, Luis
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EVOKED potentials (Electrophysiology) , *ELECTROPHYSIOLOGY , *ELECTROENCEPHALOGRAPHY , *PAIN , *LASERS , *INFRARED technology - Abstract
Painful stimuli delivered by infrared laser stimulators elicit laser-evoked potentials (LEP) or magnetic fields in respective electroencephalogram (EEG) and magnetoencephalogram (MEG). Evidence is reviewed that LEP represent a series of event-related potentials (ERP) that depend on vigilance and arousal, selective spatial attention and contextual task variables. Paradigms adopted from other stimulus modalities in the assessment of attention and cognition in ERP and applied to LEP allow the view that middle-latency (N1) and long latency (N2–P2) components of LEP can be overlapped or supplemented by endogenous components such as the processing negativity and distinct members (P3a and P3b) of the “P300” activities, each of which is considered in detail in this review. This composite entity needs to be considered when LEP are experimentally or clinically used in the assessment of sensory and cognitive phenomena and abnormalities of pain sensation. [Copyright &y& Elsevier]
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- 2003
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39. tDCS as a procedure for chronic pain relief.
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Garcia-Larrea, Luis
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TRANSCRANIAL direct current stimulation , *CHRONIC pain , *PHARMACOLOGY , *ETIOLOGY of diseases , *CHARCOT joints , *VISITATION in hospitals - Abstract
Albeit the general notion of cortical activation via external currents has a long history of trials and failures, transcranial direct-current cortex stimulation (tDCS) has only recently been widely introduced as a neuromodulation procedure for the non-pharmacological relief of chronic pain. In non-cephalic pain syndromes, tDCS is most commonly applied over the sensori-motor or dorsolateral prefrontal cortices, via electrodes of about 35 mm 2 delivering currents not higher than 2 mA. In accordance with a theoretical model establishing that anodal currents tend to activate the underlying (motor) cortex, the anode is commonly placed over the C3/C4 scalp positions, with return of current via a cathode attached to the frontopolar region. Studies on cephalic pain (mainly migraine) have used cathodal stimulation over occipital areas, aimed at inhibiting the occipital cortex. Since current diffusivity when using bipolar montages is important, so-called “focal tDCS” montages are being increasingly used, whereby a number of return points are disposed around the ‘active’ electrode. A recent literature review on tDCS results in more than 1.300 patients treated with tDCS for chronic pain of different aetiologies was unable to propose any ‘A-level’ (i.e. ‘certain efficacy’) recommendation, but suggested a B-level (probable efficacy) of anodal stimulation over M1 in fibromyalgia, and a C-level (possible efficacy) for motor cortex tDCS in neuropathic lower limb pain due to spinal injury. The pain relieving effects of tDCS appear slightly lower than those of rTMS (itself less powerful than epidural stimulation), but some studies have reported tDCS-induced pain relief in patients previously resistant to rTMS. A substantial practical advantage of tDCS is the possibility of implementing home-based stimulation systems, controlled by doctors via an Internet connection, thus avoiding the burden of iterative hospital visits. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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40. Transcranial direct current stimulation of 3 cortical targets is no more effective than placebo as treatment for fibromyalgia: a double-blind sham-controlled clinical trial.
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Samartin-Veiga, Noelia, Pidal-Miranda, Marina, González-Villar, Alberto J., Bradley, Claire, Garcia-Larrea, Luis, O'Brien, Anthony T., and Carrillo-de-la-Peña, María T.
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TREATMENT of fibromyalgia , *FRONTAL lobe , *RESEARCH , *PAIN , *PAIN measurement , *RESEARCH methodology , *EVALUATION research , *FIBROMYALGIA , *COMPARATIVE studies , *RANDOMIZED controlled trials , *TRANSCRANIAL direct current stimulation , *BLIND experiment , *FATIGUE (Physiology) , *DISEASE complications - Abstract
Abstract: Transcranial direct current stimulation (tDCS) over the primary motor cortex (M1) and the dorsolateral prefrontal cortex seem to improve pain and other symptoms of fibromyalgia (FM), although the evidence on the effectiveness of tDCS and the optimal stimulation target is not robust enough. Our main objective was to establish the optimal area of stimulation, comparing the 2 classical targets and a novel pain-related area, the operculo-insular cortex, in a sham-controlled trial. Using a double-blind design, we randomly assigned 130 women with FM to 4 treatment groups (M1, dorsolateral prefrontal cortex, operculo-insular cortex, and sham), each receiving fifteen 20-minute sessions of 2 mA anodal tDCS over the left hemisphere. Our primary outcome was pain intensity. The secondary outcomes were the other core symptoms of FM (fatigue, mood, cognitive and sleep disorders, and hyperalgesia measured by the pressure pain threshold). We performed the assessment at 3 time points (before, immediately after treatment, and at 6 months follow-up). The linear mixed-model analysis of variances showed significant treatment effects across time for clinical pain and for fatigue, cognitive and sleep disturbances, and experimental pain, irrespective of the group. In mood, the 3 active tDCS groups showed a significantly larger improvement in anxiety and depression than sham. Our findings provide evidence of a placebo effect, support the use of tDCS for the treatment of affective symptoms, and challenge the effectiveness of tDCS as treatment of FM. [ABSTRACT FROM AUTHOR]- Published
- 2022
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41. The N13 spinal component of somatosensory evoked potentials is modulated by heterotopic noxious conditioning stimulation suggesting an involvement of spinal wide dynamic range neurons.
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Pietro, Giuseppe Di, Stefano, Giulia Di, Leone, Caterina, Lionardo, Andrea Di, Sgrò, Emanuele, Blockeel, Anthony James, Caspani, Ombretta, Garcia-Larrea, Luis, Mouraux, André, Phillips, Keith Geoffrey, Treede, Rolf-Detlef, Valeriani, Massimiliano, and Truini, Andrea
- Subjects
- *
SOMATOSENSORY evoked potentials , *NEURONS , *NEURAL stimulation , *PAIN threshold , *MEDIAN nerve , *SPINAL cord - Abstract
Although somatosensory evoked potentials (SEPs) after median nerve stimulation are widely used in clinical practice, the dorsal horn generator of the N13 SEP spinal component is not clearly understood. To verify whether wide dynamic range neurons in the dorsal horn of the spinal cord are involved in the generation of the N13 SEP, we tested the effect of heterotopic noxious conditioning stimulation, which modulates wide dynamic range neurons, on N13 SEP in healthy humans. In 12 healthy subjects, we performed the cold pressor test on the left foot as a heterotopic noxious conditioning stimulus to modulate wide dynamic range neurons. To verify the effectiveness of heterotopic noxious conditioning stimulation, we tested the pressure pain threshold at the thenar muscles of the right hand and recorded SEPs after right median nerve stimulation before, during and after the cold pressor test. The cold pressor test increased pressure pain threshold by 15% (p = 0.04). During the cold pressor test, the amplitude of the N13 component was significantly lower than that recorded at baseline (by 25%, p = 0.04). In this neurophysiological study in healthy humans, we showed that a heterotopic noxious conditioning stimulus significantly reduced N13 SEP amplitude. This finding suggests that the N13 SEP might be generated by the segmental postsynaptic response of dorsal horn wide dynamic range neurons. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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- View/download PDF
42. Contextual modulation of autonomic pain reactivity.
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Fauchon, Camille, Pichot, Vincent, Faillenot, Isabelle, Pommier, Benjamin, Garcia-Larrea, Luis, Peyron, Roland, and Chouchou, Florian
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- *
NOCICEPTIVE pain , *STIMULUS & response (Biology) , *CARDIOVASCULAR system , *WAVELETS (Mathematics) , *AUTONOMIC nervous system - Abstract
Although modulation of cardiac activity may be influenced by several factors, interaction between autonomic nociceptive responses and the high-level of cortical processes is not clearly understood. Here, we studied in 26 subjects whether empathetic or unempathetic contexts could interact with autonomic pain responses. RR intervals variability was used to approach parasympathetic and sympathetic responses to painful thermal stimulations, according to contexts evoked by experimenters' comments. We observed that unempathetic context increased sympathetic reactivity to comments and to painful stimulations without any parasympathetic change. These results show an interaction between context and nociceptive processes in cardiovascular control. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
43. Differential effect of motor cortex stimulation on unit activities in the ventral posterior lateral thalamus in cats.
- Author
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Kobaïter-Maarrawi, Sandra, Maarrawi, Joseph, Saadé, Nayef, Garcia-Larrea, Luis, and Magnin, Michel
- Subjects
- *
NOCICEPTORS , *MOTOR cortex , *ANALGESICS , *THALAMUS , *HEALTH outcome assessment , *ANATOMY - Abstract
Although motor cortex stimulation (MCS) is being increasingly used to treat chronic refractory neuropathic pain in humans, its mechanisms of action remain elusive. Studies in animals have suggested the involvement of subcortical structures, in particular, the thalamus. Most of these studies have been performed in rats, a species presenting significant differences in thalamic anatomy and function relative to primates, in particular, a very limited number of thalamic GABA interneurons. The aim of this study was to investigate the effects of MCS on single-unit activities of the thalamic ventral posterior lateral (VPL) nucleus in cats, which contains substantial numbers of GABA interneurons. Spontaneous and evoked activities of VPL units were studied before and after MCS. Motor cortex stimulation induced significant depression of the wide-dynamic-range (WDR) cells' firing rate, concomitant with activity enhancement of nonnociceptive (NN) units. More than half of WDR cells showed a significant decrease in the firing rate, while a similar proportion of NN units exhibited the opposite after-effect. Maximal firing attenuation of WDR cells occurred when the MCS location matched somatotopically their receptive field. Repetition of MCS runs led to an accentuation of WDR depression. After peripheral stimulation, evoked activity in each cell showed MCS effects similar to those observed in spontaneous activity. These data demonstrate a selective top-down inhibition by MCS of nonspecific nociceptive (WDR) cells, enhanced by somatotopic concordance and stimulation repetition, in parallel to facilitation of NN cells. These 2 outcomes may play a role in the complex analgesic effect of MCS observed in neuropathic pain conditions. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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44. Painful Sensory Neuropathy.
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Truini, Andrea, Cruccu, Giorgio, and Garcia-Larrea, Luis
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LETTERS to the editor , *PAIN - Abstract
A letter to the editor is presented in response to the article "Painful Sensory Neuropathy," by J. R. Mendell and Z. Sahenk in the 2003 issue.
- Published
- 2003
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45. Differential brain opioid receptor availability in central and peripheral neuropathic pain
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Maarrawi, Joseph, Peyron, Roland, Mertens, Patrick, Costes, Nicolas, Magnin, Michel, Sindou, Marc, Laurent, Bernard, and Garcia-Larrea, Luis
- Subjects
- *
OPIOID receptors , *PAIN , *THALAMUS , *TOMOGRAPHY - Abstract
Abstract: This study used positron emission tomography (PET) and [11C]diprenorphine to compare the in vivo distribution abnormalities of brain opioid receptors (OR) in patients with peripheral (n =7) and central post-stroke pain (CPSP, n =8), matched for intensity and duration. Compared with age- and sex-matched controls, peripheral neuropathic pain (NP) patients showed bilateral and symmetrical OR binding decrease, while in CPSP binding decrease predominated in the hemisphere contralateral to pain. In CPSP patients, interhemispheric comparison demonstrated a significant decrease in opioid binding in posterior midbrain, medial thalamus and the insular, temporal and prefrontal cortices contralateral to the painful side. Peripheral NP patients did not show any lateralised decrease in opioid binding. Direct comparison between the central and peripheral groups confirmed a significant OR decrease in CPSP, contralateral to pain. While bilateral binding decrease in both NP groups may reflect endogenous opioid release secondary to chronic pain, the more important and lateralised decrease specific to CPSP suggests opioid receptor loss or inactivation in receptor-bearing neurons. Opioid binding decrease was much more extensive than brain anatomical lesions, and was not co-localised with them; metabolic depression (diaschisis) and/or degeneration of OR neurons-bearing secondary to central lesions appears therefore as a likely mechanism. Central and peripheral forms of NP may differ in distribution of brain opioid system changes and this in turn might underlie their different sensitivity to opiates. [Copyright &y& Elsevier]
- Published
- 2007
- Full Text
- View/download PDF
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