Cortical disinhibition occurs in chronic neuropathic, but not in chronic nociceptive pain

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to examine the relationship between chronic neuropathic pain after incomplete peripheral nerve lesion, chronic nociceptive pain due to osteoarthritis, and the excitability of the motor cortex assessed by transcranial magnetic stimulation (TMS). Hence in 26 patients with neuropathic pain resulting from an isolated incomplete lesion of the median or ulnar nerve (neuralgia), 20 patients with painful osteoarthritis of the hand, and 14 healthy control subjects, the excitability of the motor cortex was tested using paired-pulse TMS to assess intracortical inhibition and facilitation. These excitability parameters were compared between groups, and the relationship between excitability parameters and clinical parameters was examined.</p> <p>Results</p> <p>We found a significant reduction of intracortical inhibition in the hemisphere contralateral to the lesioned nerve in the neuralgia patients. Intracortical inhibition in the ipsilateral hemisphere of neuralgia patients and in both hemispheres of osteoarthritis patients did not significantly differ from the control group. Disinhibition was significantly more pronounced in neuralgia patients with moderate/severe pain intensity than in patients with mild pain intensity, whereas the relative compound motor action potential as a parameter of nerve injury severity did not correlate with the amount of disinhibition.</p> <p>Conclusions</p> <p>Our results suggest a close relationship between motor cortex inhibition and chronic neuropathic pain in the neuralgia patients, which is independent from nerve injury severity. The lack of cortical disinhibition in patients with painful osteoarthritis points at differences in the pathophysiological processes of different chronic pain conditions with respect to the involvement of different brain circuitry.</p

Evidence for Thalamic Involvement in the Thermal Grill Illusion: An fMRI Study

Perceptual illusions play an important role in untangling neural mechanisms underlying conscious phenomena. The thermal grill illusion (TGI) has been suggested as a promising model for exploring percepts involved in neuropathic pain, such as cold-allodynia (pain arising from contact with innocuous cold). The TGI is an unpleasant/painful sensation from touching juxtapositioned bars of cold and warm innocuous temperatures.To develop an MRI-compatible TGI-unit and explore the supraspinal correlates of the illusion, using fMRI, in a group of healthy volunteers.We constructed a TGI-thermode allowing the rapid presentation of warm(41°C), cold(18°C) and interleaved(41°C+18°C = TGI) temperatures in an fMRI-environment. Twenty volunteers were tested. The affective-motivational (“unpleasantness”) and sensory-disciminatory (“pain-intensity”) dimensions of each respective stimulus were rated. Functional images were analyzed at a corrected α-level <0.05.The TGI was rated as significantly more unpleasant and painful than stimulation with each of its constituent temperatures. Also, the TGI was rated as significantly more unpleasant than painful. Thermal stimulation versus neutral baseline revealed bilateral activations of the anterior insulae and fronto-parietal regions. Unlike its constituent temperatures the TGI displayed a strong activation of the right (contralateral) thalamus. Exploratory contrasts at a slightly more liberal threshold-level also revealed a TGI-activation of the right mid/anterior insula, correlating with ratings of unpleasantness(rho = 0.31).To the best of our knowledge, this is the first fMRI-study of the TGI. The activation of the anterior insula is consistent with this region's putative role in processing of homeostatically relevant feeling-states. Our results constitute the first neurophysiologic evidence of thalamic involvement in the TGI. Similar thalamic activity has previously been observed during evoked cold-allodynia in patients with central neuropathic pain. Our results further the understanding of the supraspinal correlates of the TGI-phenomenon and pave the way for future inquiries into if and how it may relate to neuropathic pain

Relapses in Patients Treated with High-Dose Biotin for Progressive Multiple Sclerosis

High-dose biotin (HDB) is a therapy used in non-active progressive multiple sclerosis (PMS). Several reports have suggested that HDB treatment may be associated with an increased risk of relapse. We aimed to determine whether HDB increases the risk of clinical relapse in PMS and describe the characteristics of the patients who experience it. We conducted a French, multicenter, retrospective study, comparing a group of PMS patients treated with HDB to a matched control group. Poisson regression was applied to model the specific statistical distribution of the annualized relapse rate (ARR). A propensity score (PS), based on the inverse probability of treatment weighting (IPTW), was used to adjust for indication bias and included the following variables: gender, primary PMS or not, age, EDSS, time since the last relapse, and co-prescription of a DMT. Two thousand six hundred twenty-eight patients treated with HDB and 654 controls were analyzed with a follow-up of 17 ± 8 months. Among them, 148 validated relapses were observed in the group treated with biotin and 38 in the control group (p = 0.62). After adjustment based on the PS, the ARR was 0.044 ± 0.23 for the biotin-treated group and 0.028 ± 0.16 for the control group (p = 0.18). The more relapses there were before biotin, the higher the risk of relapse during treatment, independently from the use of HDB. While the number of relapses reported for patients with no previous inflammatory activity receiving biotin has gradually increased, the present retrospective study is adequately powered to exclude an elevated risk of relapse for patients with PMS treated with HDB.Observatoire Français de la Sclérose en Plaque

The Distressed Brain: A Group Blind Source Separation Analysis on Tinnitus

Background: Tinnitus, the perception of a sound without an external sound source, can lead to variable amounts of distress. Methodology: In a group of tinnitus patients with variable amounts of tinnitus related distress, as measured by the Tinnitus Questionnaire (TQ), an electroencephalography (EEG) is performed, evaluating the patients ’ resting state electrical brain activity. This resting state electrical activity is compared with a control group and between patients with low (N = 30) and high distress (N = 25). The groups are homogeneous for tinnitus type, tinnitus duration or tinnitus laterality. A group blind source separation (BSS) analysis is performed using a large normative sample (N = 84), generating seven normative components to which high and low tinnitus patients are compared. A correlation analysis of the obtained normative components ’ relative power and distress is performed. Furthermore, the functional connectivity as reflected by lagged phase synchronization is analyzed between the brain areas defined by the components. Finally, a group BSS analysis on the Tinnitus group as a whole is performed. Conclusions: Tinnitus can be characterized by at least four BSS components, two of which are posterior cingulate based, one based on the subgenual anterior cingulate and one based on the parahippocampus. Only the subgenual component correlates with distress. When performed on a normative sample, group BSS reveals that distress is characterized by two anterior cingulate based components. Spectral analysis of these components demonstrates that distress in tinnitus is relate

Interoception across Modalities: On the Relationship between Cardiac Awareness and the Sensitivity for Gastric Functions

The individual sensitivity for ones internal bodily signals (“interoceptive awareness”) has been shown to be of relevance for a broad range of cognitive and affective functions. Interoceptive awareness has been primarily assessed via measuring the sensitivity for ones cardiac signals (“cardiac awareness”) which can be non-invasively measured by heartbeat perception tasks. It is an open question whether cardiac awareness is related to the sensitivity for other bodily, visceral functions. This study investigated the relationship between cardiac awareness and the sensitivity for gastric functions in healthy female persons by using non-invasive methods. Heartbeat perception as a measure for cardiac awareness was assessed by a heartbeat tracking task and gastric sensitivity was assessed by a water load test. Gastric myoelectrical activity was measured by electrogastrography (EGG) and subjective feelings of fullness, valence, arousal and nausea were assessed. The results show that cardiac awareness was inversely correlated with ingested water volume and with normogastric activity after water load. However, persons with good and poor cardiac awareness did not differ in their subjective ratings of fullness, nausea and affective feelings after drinking. This suggests that good heartbeat perceivers ingested less water because they subjectively felt more intense signals of fullness during this lower amount of water intake compared to poor heartbeat perceivers who ingested more water until feeling the same signs of fullness. These findings demonstrate that cardiac awareness is related to greater sensitivity for gastric functions, suggesting that there is a general sensitivity for interoceptive processes across the gastric and cardiac modality

Migraine in multiple sclerosis and other chronic inflammatory diseases

International audienc

Neurostimulation methods in the treatment of chronic pain

International audienc

P26 - Risque de poussée après vaccination contre le COVID-19 chez les patients atteints de sclérose en plaques en France utilisant un design « self-controlled case series »

International audienceIntroductionLes patients avec sclérose en plaques (SEP) ont eu un accès prioritaire à la vaccination contre le SARS-CoV-2. De nombreux cas de poussées subséquents à la vaccination ont été reportés dans la littérature, décourageant les patients à recevoir la dose de rappel, dans cette population parfois déjà réticente. L'objectif de cette étude était d’évaluer le risque de poussée suivant la vaccination contre le COVID-19 dans la population de patients avec SEP en France.MéthodesL’étude a été réalisée en utilisant les données du Système national des données de santé (SNDS). Les patients avec SEP ont été identifiés sur la base d'une affection de longue durée (ALD) pour SEP via un code CIM-10 ou traitement spécifique et suivis jusqu'en mars 2022. Les poussées nécessitant des corticoïdes à hautes doses ont été identifiées en utilisant un algorithme précédemment publié. Un design de type « self-controlled case series » (SCCS) a été utilisé pour évaluer le risque de poussée dans les 45 jours suivant la vaccination (analyse de sensibilité avec 90 jours). Le risque a été évalué pour la première, deuxième et troisième (rappel) dose et exprimé sous la forme d'un ratio du taux d'incidence (IRR), en prenant en compte les potentiels biais liés à des critères variants dans le temps tels que la saisonnalité et les traitements de fond de la SEP.RésultatsAu total, 124.545 patients avec SEP ont été identifiés au 1er janvier 2021, dont 82,3 % (n=102 524) ont reçu au moins une dose de vaccin contre le COVID-19 au 31 décembre 2021, pour un total de 259 880 doses. Aucune majoration du risque de poussée n'a été constatée pour les 1e, 2e et 3e doses, pour un effet combiné donnant un IRR=0,97 [0,91–1,03], p=0,30. Cette absence de risque était aussi valable pour les sous-groupes (âge <50ans, ancienneté de la SEP <10 ans, patients utilisant des traitements de fond de la maladie). Une légère augmentation du risque de poussée a été remarquée après la dose de rappel pour les patients fortement inflammatoires (au moins deux poussées sur les deux années précédentes), principalement portée par les patients non traités, là où les traités n'avaient pas d'augmentation significative du risque.ConclusionDans cette étude d'envergure nationale sur plus de 100 000 patients avec SEP, nous n'avons pas trouvé d'augmentation du risque de poussée nécessitant l'utilisation de corticothérapie, suivant une vaccination contre le COVID-19. La vaccination contre le COVID-19 peut donc être recommandée chez les patients vivant avec une SEP les plus à risque d'infection sévère, avec une prudence toutefois pour les patients avec une forte activité inflammatoire et qui devraient être traités