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Background and Objective: Pain influences motor control. Previous reviews observed that pain reduces the excitability of corticospinal projections to muscles tested with transcranial magnetic stimulation. However, the independent effect of the type of pain models (tonic, phasic), pain location and tissues targeted (e.g. muscle, skin) remains unexplored. The objective of this review was to determine the influence of experimental pain and of different methodological factors on the corticospinal excitability., Databases and Data Treatment: Three electronic databases were searched: Embase, Pubmed and Web of Science. Meta-analyses were conducted in three consecutive steps to reduce methodological variability: (a) all studies; (b) same pain location; (c) same tissues, pain location and muscle state. Strength of evidence was assessed for each analysis performed., Results: Forty studies were included in the review and 26 in the meta-analysis as it focused only on studies using tonic pain. Overall, there was conflicting/moderate evidence of a diminution of corticospinal excitability during and after tonic pain. When considering only pain location, tonic hand and face pain induced a reduction in corticospinal excitability (limited evidence). Both muscle and cutaneous hand pain reduced corticospinal excitability (limited/conflicting evidence). Similar results were observed for phasic pain (limited evidence)., Conclusions: Our results confirm the inhibitory effect of pain on corticospinal excitability for both tonic and phasic pain. This reduction was specific to hand and face pain. Also, both cutaneous and muscle hand pain reduced excitability. The strength of evidence remains limited/conflicting. More high-quality studies are needed to confirm our conclusions., Significance: This study adds evidence on the effect of specific factors on the modulation of corticospinal excitability during/after experimental pain. The reduction in corticospinal excitability was driven by hand and face pain. We confirmed previous results that muscle pain reduces corticospinal excitability and provided evidence of a similar effect for cutaneous pain. Both models may inform on the influence of different types of pain on motor control. Future studies are needed to determine the origin of the effect of pain., (© 2021 European Pain Federation - EFIC®.)

Background: Sensorimotor conflicts are well known to induce sensory disturbances. However, explanations as to why patients with chronic pain are more sensitive to sensorimotor conflicts remain elusive. The main objectives of this study were (a) to assess and compare the sensory disturbances induced by sensorimotor conflict in complex regional pain syndrome (n = 38), fibromyalgia (n = 36), arthritis (n = 34) as well as in healthy volunteers (HV) (n = 32); (b) to assess whether these disturbances were related to the intensity and duration of pain, or to other clinical variables assessed using questionnaires (abnormalities in sensory perception, depression and anxiety); and (c) to categorize different subgroups of conflict-induced sensory disturbances., Methods: One hundred and forty participants performed in phase or anti-phase movements with their arms while viewing a reflection of one arm in a mirror (and the other arm obscured). They were asked to report changes in sensory disturbances using a questionnaire., Results: First, results showed that patients with complex regional pain syndrome and fibromyalgia were more prone to report sensory disturbances than arthritis patients and HV in response to conflicts (small effect size). Second, conflict-induced sensory disturbances were correlated with pain intensity (large effect size) and abnormalities in sensory perception (only in the CRPS group) but were not related to the duration of the disease or psychological factors. Finally, we identified two distinct subgroups of conflict-induced sensory disturbances., Conclusions: Our results suggest that pain lowers the threshold for the detection of sensorimotor conflicts, a phenomenon that could contribute to the maintenance of pain in clinical populations., Significance: Individuals with complex regional pain syndrome and fibromyalgia were more sensitive to sensorimotor conflicts than arthritis patients and controls. Moreover, conflict-induced sensory disturbances were specific to higher pain intensity and higher sensory abnormalities in all groups, suggesting that pain lowers the threshold for the detection of sensorimotor conflicts., (© 2018 European Pain Federation - EFIC®.)

Background: The ability of growth hormone (GH) to promote the weaning-off of parenteral nutrition (PN) in short bowel syndrome (SBS) is unclear. No randomized controlled study is available in children. This study was undertaken to determine if GH could enhance the weaning off of PN in PN-dependent children with SBS., Methods: A prospective randomized open-label multicenter study was performed in 14 patients (mean age, 9 ± 1.4 years) with SBS (average small bowel length, 33 cm) and long-term PN dependency (8 years) on an unrestricted diet. A standardized PN decrease with and without GH (0.14 mg/kg/d) was conducted. The patients were randomized to either a GH group (4 months of GH) or a control (CTR) group (4 months without GH, followed by 4 months with GH). Blood tests and a nutrition assessment of enteral and parenteral intakes were performed. Groups were compared with the Wilcoxon test., Results: Treatment with GH did not improve the weaning off of PN (decrease in PN caloric intake of 32.5% ± 9.6% in the GH group vs 35.2% ± 8.7% in the CTR group, nonsignificant). In the CTR group, GH treatment induced an additional but not statistically significant decrease of 8.8% ± 12.4% in daily calories. Parenteral needs returned to near basal rates 6 months after GH discontinuation (GH: 77.6% ± 10.6% vs CTR: 73.2% ± 7.4%). Weight decreased slightly in both groups. No biological parameters varied significantly., Conclusions: GH did not improve the weaning off of PN in PN-dependent children with SBS.

It is generally considered that hand amputation changes primary motor cortex (M1) stump muscle representations. Transcranial magnetic stimulation (TMS) studies show that the corticospinal excitability of a stump muscle and its homologous muscle on the intact side is not equivalent, and that the resting level of excitability is higher in the stump muscle. Since changes in M1 stump muscle map characteristics (e.g., size and location) are identified by comparing stump and intact muscle maps, such changes might reflect between-side differences in corticospinal excitability rather than a true reorganization of the stump muscle's map. In eight above-elbow amputees we used TMS to map the M1 representation of a stump muscle and its homologous muscle on the intact side during rest and contraction. Importantly, the same relative stimulation intensity was used to construct each map; stimulation was performed at 120% of the motor threshold of each muscle (intact/amputated limb) measured in each condition (rest/active contraction). Resting motor threshold was lower in the stump muscle, but active motor thresholds did not differ. Motor-evoked potential amplitudes increased between the rest and muscle contraction conditions, but this increase was smaller for the stump muscle because its at-rest corticospinal excitability was higher than that of the intact muscle. When the between-side difference in excitability was considered no interhemispheric difference was found for map areas or for their medio-lateral locations. The present results challenge the view that after an upper limb amputation the stump representation moves laterally and occupies a larger M1 territory., (Copyright © 2010 Wiley-Liss, Inc.)

A critical step in infection by the apicomplexan parasite Toxoplasma gondii is the formation of a membrane-bound compartment within which the parasite proliferates. This process relies on a set of secretory organelles that discharge their contents into the host cell upon invasion. Among these organelles, the dense granules are specialized in the export of transmembrane (TM) GRA proteins, which are major components of the mature parasitophorous vacuole (PV) membrane. How eukaryotic pathogens export and sort membrane-bound proteins destined for the host cell is still poorly understood at the mechanistic level. In this study, we show that soluble trafficking of the PV-targeted GRA5 TM protein is parasite specific: when expressed in mammalian cells, GRA5 is targeted to the plasma membrane and behaves as an integral membrane protein with a type I toplogy. We also demonstrate the dual role of the GRA5 N-terminal ectodomain, which is sufficient to prevent membrane integration within the parasite and is essential for both sorting and post-secretory membrane insertion into the vacuolar membrane. These results contrast with the general rule that states that information contained within the cytoplasmic tail and/or the TM domain of integral membrane proteins dictates their cellular localization. They also highlight the diversity of sorting mechanisms that leads to the specialization of secretory processes uniquely adapted to intracellular parasitism.

Neural activity in the motor cortex and its descending projections is modulated in a task-related manner. Several TMS studies have shown that when normal human subjects execute different manual tasks requiring similar contraction levels in first dorsal interroseous (FDI) there is a task-related modulation of the amplitude of FDI motor evoked potentials (MEPs). Not all studies of task-related changes show the same pattern of results, however. One reason for this might be methodological. Studies have assessed task-related changes by stimulating a single site, which can provide information about task-related changes in the excitability of the cortex at that site, but which is not sensitive to excitability changes throughout the muscle's cortical representation. We investigated how the execution of an individuated versus a nonindividuated isometric grasping task affected the excitability of FDI's entire cortical representation. We examined FDI MEP amplitudes while subjects grasped an object between their thumb and index finger, or when they grasped the same object between their thumb and all four fingers, keeping the background level of EMG in FDI constant for the two tasks. We found no overall task-related change in the excitability of FDI or its cortical topography, possibly due to behavioral differences of individual subjects. The stability of FDI's cortical representation during two different manual tasks expands the possibilities for studying cortical reorganization in the context of active muscle contraction, which will enable us to better understand whether changes in the motor system observed when muscles are at rest are also present during voluntary muscle recruitment., ((Copyright) 2006 Wiley-Liss, Inc.)

Most Apicomplexa reside and multiply in the cytoplasm of their host cell, within a parasitophorous vacuole (PV) originating from both parasite and host cell components. Trafficking of parasite-encoded proteins destined to membrane compartments beyond the confine of the parasite plasma membrane is a process that offers a rich territory to explore novel mechanisms of protein-membrane interactions. Here, we focus on the PVs formed by the asexual stages of two pathogens of medical importance, Plasmodium and Toxoplasma. We compare the PVs of both parasites, with a particular emphasis on their evolutionary divergent compartmentalization within the host cell. We also discuss the existence of peculiar export mechanisms and/or sorting determinants that are potentially involved in the post-secretory targeting of parasite proteins to the PV subcompartments.

Background: Surgical removal and radiation therapy are associated with significant risk for morbidity in the pediatric population with craniopharyngioma. Intracystic therapies have been utilized in some centers to potentially decrease morbidity associated with cystic craniopharyngioma. The aim of the study was to review the Canadian experience with intracystic bleomycin therapy (ICB)., Methods: All centers in the Canadian Pediatric Brain Tumor Consortium (CPBTC) were invited to participate in a retrospective review of this treatment. A questionnaire was sent to each center. The data were analyzed at British Columbia's Children's Hospital., Results: In all, 6 of 17 centers utilized ICB and submitted data. A total of 17 of 19 patients with the intention to treat received bleomycin. Twelve were treated at the time of diagnosis, and 5 at the time of recurrence. Five patients achieved a complete response, 6 achieved a partial response, and 5 achieved a minor response to bleomycin. One patient was stable for 2.8 years. At the time of last follow-up, 8 patients have not required further intervention. Complications included transient symptomatic peritumoral edema (2 patients), precocious puberty (1 patient) and panhypopituitarism (2 patients). The median follow-up was 4 years (range, 0.5-10.2 years). The median progression-free survival was 1.8 years (range, 0.3-6.1 years). One patient died of a massive infarct secondary to radiation-induced moyamoya syndrome., Conclusions: ICB was found to be well tolerated in this group of children. ICB may be a feasible and effective therapy for certain children with craniopharyngioma. Bleomycin may delay the need for aggressive surgery or radiation therapy for several years. Prospective multiinstitutional clinical trials are required to further evaluate the feasibility, effectiveness, and dose schedules of this treatment., ((c) 2007 American Cancer Society)