Arthurcovington3749

© 2020 American Academy of Neurology.OBJECTIVE To determine whether Scrambler therapy is an effective, acceptable, and feasible treatment of persistent central neuropathic pain in patients with neuromyelitis optica spectrum disorder (NMOSD) and to explore the effect of Scrambler therapy on co-occurring symptoms. click here METHODS We conducted a randomized single-blind, sham-controlled trial in patients with NMOSD who have central neuropathic pain using Scrambler therapy for 10 consecutive weekdays. Pain severity, pain interference, anxiety, depression, and sleep disturbance were assessed at baseline, at the end of treatment, and at the 30- and 60-day follow-up. RESULTS Twenty-two patients (11 per arm) were enrolled in and completed this trial. The median baseline numeric rating scale (NRS) pain score decreased from 5.0 to 1.5 after 10 days of treatment with Scrambler therapy, whereas the median NRS score did not significantly decrease in the sham arm. Depression was also reduced in the treatment arm, and anxiety was decreased in a subset of patients who responded to treatment. These symptoms were not affected in the sham arm. The safety profiles were similar between groups. CONCLUSIONS Scrambler therapy is an effective, feasible, and safe intervention for central neuropathic pain in patients with NMOSD. Decreasing pain with Scrambler therapy may additionally improve depression and anxiety. CLINICALTRIALSGOV IDENTIFIER NCT03452176. CLASSIFICATION OF EVIDENCE This study provides Class II evidence that Scrambler therapy significantly reduces pain in patients with NMOSD and persistent central neuropathic pain. © 2020 American Academy of Neurology.Calcineurin inhibitors, such as tacrolimus (FK506) and cyclosporine, are widely used as standard immunosuppressants in organ transplantation recipients. However, these drugs can cause severe pain in patients, commonly referred to as calcineurin inhibitor-induced pain syndrome (CIPS). Although calcineurin inhibition increases N-methyl-D-aspartate receptor (NMDAR) activity in the spinal cord, the underlying mechanism remains enigmatic. Using an animal model of CIPS, we found that systemic administration of FK506 in male and female mice significantly increased the amount of α2δ-1-GluN1 complexes in the spinal cord and the level of α2δ-1-bound GluN1 proteins in spinal synaptosomes. Treatment with FK506 significantly increased the frequency of miniature excitatory postsynaptic currents (EPSCs) and the amplitudes of monosynaptic EPSCs evoked from the dorsal root and puff NMDAR currents in spinal dorsal horn neurons. Inhibiting α2δ-1 with gabapentin or disrupting the α2δ-1-NMDAR interaction with α2δ-1Tat peptide comin inhibition enhances physical interaction between α2δ-1 and NMDA receptors and their synaptic trafficking in the spinal cord. α2δ-1 is essential for calcineurin inhibitor-induced aberrant activation of presynaptic and postsynaptic NMDA receptors in the spinal cord. Furthermore, inhibiting α2δ-1 or disrupting α2δ-1-NMDA receptor interaction reduces calcineurin inhibitor-induced pain hypersensitivity. Eliminating NMDA receptors in primary sensory neurons or α2δ-1 knockout also attenuates calcineurin inhibitor-induced pain hypersensitivity. This new information extends our mechanistic understanding of the role of endogenous calcineurin in regulating synaptic plasticity and nociceptive transmission and suggests new strategies for treating this painful condition. Copyright © 2020 Huang et al.MECP2 gain- and loss-of-function in genetically-engineered monkeys recapitulates typical phenotypes in autism, yet where MECP2 mutation affects the monkey brain and whether/how it relates to autism pathology remains unknown. Here we report a combination of gene-circuit-behavior analyses including MECP2 co-expression network, locomotive and cognitive behaviors, EEG and fMRI in five MECP2 overexpressed (Macaca fascicularis; 3 female) and twenty wild-type (Macaca fascicularis; 11 female) monkeys. Whole-genome expression analysis revealed MECP2 co-expressed genes significantly enriched in GABA-related signaling pathways, whereby reduced beta synchronization within fronto-parieto-occipital networks was associated with abnormal locomotive behaviors. Meanwhile, MECP2-induced hyper-connectivity in prefrontal and cingulate networks accounted for regressive deficits in reversal learning tasks. Furthermore, we stratified a cohort of 49 autisms and 72 controls out of 1112 subjects using functional connectivity patterns, mapped to a homogeneous ASD subgroup, thereby offering a new strategy to deconstruct clinical heterogeneity in ASD. Copyright © 2020 Cai et al.Emerging evidence suggests that there is a reduction in overall cortical excitatory to inhibitory balance in major depressive disorder (MDD), which afflicts approximately 14-20% of individuals. Reduced pyramidal cell arborization occurs with stress and MDD, and may diminish excitatory neurotransmission. Enhanced deposition of perineuronal net (PNN) components also occurs with stress. Since parvalbumin-expressing interneurons are the predominant cell population that is enveloped by PNNs, which enhance their ability to release GABA, excess PNN deposition likely increases pyramidal cell inhibition. In the present study we investigate the potential for matrix metalloprotease-9 (MMP-9), an endopeptidase secreted in response to neuronal activity, to contribute to the antidepressant efficacy of the serotonin/norepinephrine reuptake inhibitor venlafaxine in male mice. Chronic venlafaxine increases MMP-9 levels in murine cortex, and increases both pyramidal cell arborization and PSD-95 expression in the cortex of wildnvestigate a potential role for an extracellular protease, released from neurons and known to play a role in learning and memory, in anti-depressant-associated increases in excitatory transmission. Our data suggests that this protease, MMP-9, increases branching of excitatory neurons and concomitantly attenuates the perineuronal net to potentially reduce inhibitory input to these neurons. MMP-9 may thus enhance overall excitatory/inhibitory balance and neuronal population dynamics that are important to mood and memory. Copyright © 2020 Alaiyed et al.