Phenotypes of Motor Deficit and Pain after Experimental Spinal Cord Injury.
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ABSTRACT:
SUBMITTER: Krotov V
PROVIDER: S-EPMC9220047 | biostudies-literature | 2022 Jun
REPOSITORIES: biostudies-literature
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Phenotypes of Motor Deficit and Pain after Experimental Spinal Cord Injury.
Krotov Volodymyr V Medvediev Volodymyr V Abdallah Ibrahim I Bozhenko Arseniy A Tatarchuk Mykhailo M Ishchenko Yevheniia Y Pichkur Leonid L Savosko Serhii S Tsymbaliuk Vitaliy V Kopach Olga O Voitenko Nana N
Bioengineering (Basel, Switzerland) 20220620 6
Motor disability is a common outcome of spinal cord injury (SCI). The recovery of motor function after injury depends on the severity of neurotrauma; motor deficit can be reversible, at least partially, due to the innate tissue capability to recover, which, however, deteriorates with age. Pain is often a comorbidity of injury, although its prediction remains poor. It is largely unknown whether pain can attend motor dysfunction. Here, we implemented SCI for modelling severe and moderate neurotrau ...[more]
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Project description:BackgroundPhysical and psychosocial rehabilitation following spinal cord injury (SCI) leans heavily on learning and practicing new skills. However, despite research relating motor sequence learning to spinal cord activity and clinical observations of impeded skill-learning after SCI, implicit procedural learning following spinal cord damage has not been examined.ObjectiveTo test the hypothesis that spinal cord injury (SCI) in the absence of concomitant brain injury is associated with a specific implicit motor sequence learning deficit that cannot be explained by depression or impairments in other cognitive measures.MethodsTen participants with SCI in T1-T11, unharmed upper limb motor and sensory functioning, and no concomitant brain injury were compared to ten matched control participants on measures derived from the serial reaction time (SRT) task, which was used to assess implicit motor sequence learning. Explicit generation of the SRT sequence, depression, and additional measures of learning, memory, and intelligence were included to explore the source and specificity of potential learning deficits.ResultsThere was no between-group difference in baseline reaction time, indicating that potential differences between the learning curves of the two groups could not be attributed to an overall reduction in response speed in the SCI group. Unlike controls, the SCI group showed no decline in reaction time over the first six blocks of the SRT task and no advantage for the initially presented sequence over the novel interference sequence. Meanwhile, no group differences were found in explicit learning, depression, or any additional cognitive measures.ConclusionsThe dissociation between impaired implicit learning and intact declarative memory represents novel empirical evidence of a specific implicit procedural learning deficit following SCI, with broad implications for rehabilitation and adjustment.
| S-EPMC4927174 | biostudies-literature
Project description:Study designAn experimental study.ObjectivesTo investigate the changes in somatosensory functions using the combined application of quantitative sensory testing (QST), contact heat-evoked potentials (CHEPs) and laser-evoked potentials (LEPs) studies in individuals with spinal cord injury (SCI) in relation to neuropathic pain (NeP).SettingCentre for Pain Medicine, Swiss Paraplegic Centre, Nottwil, Switzerland.MethodsIndividuals with SCI were compared: 12 with NeP (SCI NeP) and 12 without NeP (SCI no NeP). Tools used were QST, CHEPs, LEPs and self-reported questionnaires. Tests were applied to the control (hand) and test (dermatome of altered sensation) sites, and compared to the able-bodied group.ResultsQST, LEPs and CHEPs assessments showed abnormalities both on the test and control sites, which did not differ between the groups with SCI. QST showed higher prevalence of allodynia in SCI NeP. CHEPs and LEPs demonstrated diminished amplitudes in both groups with SCI in comparison to able-bodied individuals. Only reaction time (RT) analysis revealed the difference of SCI NeP from the other two groups, expressed in partially preserved responses to the laser C-fibre stimulations.ConclusionsCombination of assessments in our study allowed to examine spinothalamic and dorsal column functions in individuals with SCI. Changes in QST, CHEPs and LEPs were detected below the level of injury independent of NeP and at the control site indicating modifications in sensory processing rostral to the spinal lesion. Analysis of RT during laser stimulation could be an essential component when evaluating the somatosensory functions related to NeP in persons with SCI.
| S-EPMC8338558 | biostudies-literature
Project description:Autophagy is a catabolic process that degrades cytoplasmic constituents and organelles in the lysosome, thus serving an important role in cellular homeostasis and protection against insults. We previously reported that defects in autophagy contribute to neuronal cell damage in traumatic spinal cord injury (SCI). Recent data from other inflammatory models implicate autophagy in regulation of immune and inflammatory responses, with low levels of autophagic flux associated with pro-inflammatory phenotypes. In the present study, we examined the effects of genetically or pharmacologically manipulating autophagy on posttraumatic neuroinflammation and motor function after SCI in mice. Methods: Young adult male C57BL/6, CX3CR1-GFP, autophagy hypomorph Becn1+/- mice, and their wildtype (WT) littermates were subjected to moderate thoracic spinal cord contusion. Neuroinflammation and autophagic flux in the injured spinal cord were assessed using flow cytometry, immunohistochemistry, and NanoString gene expression analysis. Motor function was evaluated with the Basso Mouse Scale and horizontal ladder test. Lesion volume and spared white matter were evaluated by unbiased stereology. To stimulate autophagy, disaccharide trehalose, or sucrose control, was administered in the drinking water immediately after injury and for up to 6 weeks after SCI. Results: Flow cytometry demonstrated dysregulation of autophagic function in both microglia and infiltrating myeloid cells from the injured spinal cord at 3 days post-injury. Transgenic CX3CR1-GFP mice revealed increased autophagosome formation and inhibition of autophagic flux specifically in activated microglia/macrophages. NanoString analysis using the neuroinflammation panel demonstrated increased expression of proinflammatory genes and decreased expression of genes related to neuroprotection in Becn1+/- mice as compared to WT controls at 3 days post-SCI. These findings were further validated by qPCR, wherein we observed significantly higher expression of proinflammatory cytokines. Western blot analysis confirmed higher protein expression of the microglia/macrophage marker IBA-1, inflammasome marker, NLRP3, and innate immune response markers cGAS and STING in Becn1+/- mice at 3 day after SCI. Flow cytometry demonstrated that autophagy deficit did not affect either microglial or myeloid counts at 3 days post-injury, instead resulting in increased microglial production of proinflammatory cytokines. Finally, locomotor function showed significantly worse impairments in Becn1+/- mice up to 6 weeks after SCI, which was accompanied by worsening tissue damage. Conversely, treatment with a naturally occurring autophagy inducer trehalose, reduced protein levels of p62, an adaptor protein targeting cargo to autophagosomes as well as the NLRP3, STING, and IBA-1 at 3 days post-injury. Six weeks of trehalose treatment after SCI led to improved motor function recovery as compared to control group, which was accompanied by reduced tissue damage. Conclusions: Our data indicate that inhibition of autophagy after SCI potentiates pro-inflammatory activation in microglia and is associated with worse functional outcomes. Conversely, increasing autophagy with trehalose, decreased inflammation and improved outcomes. These findings highlight the importance of autophagy in spinal cord microglia and its role in secondary injury after SCI.
| S-EPMC9330534 | biostudies-literature
Project description:BackgroundThe mechanisms by which mobility function and neuropathic pain are mutually influenced by supraspinal plasticity in motor- and pain-related brain networks following spinal cord injury (SCI) remains poorly understood.ObjectiveTo determine cortical and subcortical resting-state network alterations using power spectral density (PSD) analysis and investigate the relationships between these intrinsic alterations and mobility function and neuropathic pain following SCI.MethodsA total of 41 patients with incomplete SCI and 33 healthy controls were included. The degree of mobility and balance function and severity of neuropathic pain and depressive mood were evaluated. The resting-state functional magnetic resonance imaging data of low-frequency fluctuations were analyzed based on PSD. Differences in PSD values between patients with SCI and controls were assessed using the two-sample t-test (false discovery rate-corrected P < 0.05). The relationship between PSD values and mobility function and pain intensity was assessed using Pearson's correlation coefficient adjusted for the severity of depressive mood.ResultsCompared with healthy controls, lower PSD values in supplementary motor and medial prefrontal areas (the anterior cingulate cortex, ventral medial prefrontal cortex, and superior orbito-prefrontal cortex) were associated with greater pain severity and poorer postural balance and mobility (P < 0.05) in patients with SCI, whereas higher PSD values in the primary motor cortex, premotor cortex, thalamus, and periaqueductal gray were associated with greater pain severity and poorer postural balance and mobility (P < 0.05).ConclusionsCortical and subcortical plastic alterations in intrinsic motor- and pain-related networks were observed in patients with SCI and were simultaneously associated with neuropathic pain intensity and degree of mobility function.
| S-EPMC7453139 | biostudies-literature
Project description:Spinal cord injury is associated with chronic sensorimotor deficits due to the interruption of ascending and descending tracts between the brain and spinal cord. Functional recovery after anatomically complete spinal cord injury is limited due to the lack of long-distance axonal regeneration of severed fibers in the adult central nervous system. Most spinal cord injuries in humans, however, are anatomically incomplete. Although restorative treatment options for spinal cord injury remain currently limited, research from experimental models of spinal cord injury have revealed a tremendous capability for both spontaneous and treatment-induced plasticity of the corticospinal system that supports functional recovery. We review recent advances in the understanding of corticospinal circuit plasticity after spinal cord injury and concentrate mainly on the hindlimb motor cortex, its corticospinal projections, and the role of spinal mechanisms that support locomotor recovery. First, we discuss plasticity that occurs at the level of motor cortex and the reorganization of cortical movement representations. Next, we explore downstream plasticity in corticospinal projections. We then review the role of spinal mechanisms in locomotor recovery. We conclude with a perspective on harnessing neuroplasticity with therapeutic interventions to promote functional recovery.
| S-EPMC6788232 | biostudies-literature
Project description:Chx10-expressing V2a (Chx10+V2a) spinal interneurons play a large role in the excitatory drive of motoneurons. Chemogenetic ablation studies have demonstrated the essential nature of Chx10+V2a interneurons in the regulation of locomotor initiation, maintenance, alternation, speed, and rhythmicity. The role of Chx10+V2a interneurons in locomotion and autonomic nervous system regulation is thought to be robust, but their precise role in spinal motor regulation and spinal cord injury have not been fully explored. The present paper reviews the origin, characteristics, and functional roles of Chx10+V2a interneurons with an emphasis on their involvement in the pathogenesis of spinal cord injury. The diverse functional properties of these cells have only been substantiated by and are due in large part to their integration in a variety of diverse spinal circuits. Chx10+V2a interneurons play an integral role in conferring locomotion, which integrates various corticospinal, mechanosensory, and interneuron pathways. Moreover, accumulating evidence suggests that Chx10+V2a interneurons also play an important role in rhythmic patterning maintenance, left-right alternation of central pattern generation, and locomotor pattern generation in higher order mammals, likely conferring complex locomotion. Consequently, the latest research has focused on postinjury transplantation and noninvasive stimulation of Chx10+V2a interneurons as a therapeutic strategy, particularly in spinal cord injury. Finally, we review the latest preclinical study advances in laboratory derivation and stimulation/transplantation of these cells as a strategy for the treatment of spinal cord injury. The evidence supports that the Chx10+V2a interneurons act as a new therapeutic target for spinal cord injury. Future optimization strategies should focus on the viability, maturity, and functional integration of Chx10+V2a interneurons transplanted in spinal cord injury foci.
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Project description:Increased use of epidural Spinal Cord Stimulation (eSCS) for the rehabilitation of spinal cord injury (SCI) has highlighted the need for a greater understanding of the properties of reflex circuits in the isolated spinal cord, particularly in response to repetitive stimulation. Here, we investigate the frequency-dependence of modulation of short- and long-latency EMG responses of lower limb muscles in patients with SCI at rest. Single stimuli could evoke short-latency responses as well as long-latency (likely polysynaptic) responses. The short-latency component was enhanced at low frequencies and declined at higher rates. In all muscles, the effects of eSCS were more complex if polysynaptic activity was elicited, making the motor output become an active process expressed either as suppression, tonic or rhythmical activity. The polysynaptic activity threshold is not constant and might vary with different stimulation frequencies, which speaks for its temporal dependency. Polysynaptic components can be observed as direct responses, neuromodulation of monosynaptic responses or driving the muscle activity by themselves, depending on the frequency level. We suggest that the presence of polysynaptic activity could be a potential predictor for appropriate stimulation conditions. This work studies the complex behaviour of spinal circuits deprived of voluntary motor control from the brain and in the absence of any other inputs. This is done by describing the monosynaptic responses, polysynaptic activity, and its interaction through its input-output interaction with sustain stimulation that, unlike single stimuli used to study the reflex pathway, can strongly influence the interneuron circuitry and reveal a broader spectrum of connectivity.
| S-EPMC8354937 | biostudies-literature
Project description:BackgroundThe prevalence of comorbid pain after spinal cord injury (SCI) is relatively high in clinical observations and has continued to increase over time. Neuropathic pain (70.14%) is the most popular subject in academic journals after SCI. However, studies that used the bibliometric method to analyze comorbid pain after SCI are still lacking. This study is aimed at combining and integrating acquired information to analyze the global trends of research on the comorbidity of pain after SCI in the last three decades (1990-2019).MethodsSystematic works of literature published from 1990 to 2019 were obtained from the Web of Science Core Collection. CiteSpace software was used to analyze the relationship of publication year with the country, institution, journals, authors, references, and keywords. The regression analysis is used to evaluate the percentage of the category increase or decrease over time significantly. IBM SPSS Statistics was used in the statistical analysis.ResultsA total of 730 publications were included in the analysis. A remarkable increase in the number of publications was observed in the study period (P < 0.05). A total of 202 academic journals focused on the categories of clinical neurology, neurosciences, and rehabilitation, and the annual growth rate of articles in these three categories was statistically significant (P < 0.05). The USA (356, 48.77%) and the University of Miami (64, 8.77%) were the country and institution with the highest number of publications, respectively. Spinal Cord, which was the main journal for research on pain after SCI, had the most publications (88, 12.05%). Burst keywords showed that the individual, inflammation, and central sensitization with pain after SCI are the research development trends and focus in this research field.ConclusionsOverall, this study provides the latest research direction for pain after SCI. This historical overview of research into pain after SCI will be a useful basis for further research into development trends, focus issues, cooperators, and cooperative institutions.
| S-EPMC7914384 | biostudies-literature
Project description:IntroductionNeuropathic pain is a common complication of spinal cord injury (SCI), and is notoriously difficult to adequately treat. Gunshot wounds (GSW) near the spinal cord may cause intractable chronic pain through spinal/nerve root transection, or reactive tissue formation resulting in nerve root compression from retained bullet fragments (RBF).Case presentationThis case report describes a 30-year-old man with a T12 AIS B incomplete spinal cord injury with paraplegia secondary to multiple GSW who presented with severe bilateral lower extremity dysesthesias and muscle spasms. Symptoms failed to improve with oral antispasmodic medications. After being diagnosed with Complex regional pain syndrome (CRPS) type I secondary to an SCI via GSW, he underwent a spinal cord stimulator (SCS) trial, which improved his symptoms by greater than 80%.DiscussionNeuropathic pain refractory to conservative treatment may benefit from SCS. Effects of therapy go beyond gate-theory in SCI patients, and may benefit patients at the cellular and molecular level. Our case demonstrates the effectiveness of SCS treatment in a patient who developed CRPS type 1 after GSW resulting in SCI.
| S-EPMC9478097 | biostudies-literature
Project description:BackgroundTranscutaneous spinal cord stimulation (tSCS) is a non-invasive modality in which electrodes can stimulate spinal circuitries and facilitate a motor response. This review aimed to evaluate the methodology of studies using tSCS to generate motor activity in persons with spinal cord injury (SCI) and to appraise the quality of included trials.MethodsA systematic search for studies published until May 2021 was made of the following databases: EMBASE, Medline (Ovid) and Web of Science. Two reviewers independently screened the studies, extracted the data, and evaluated the quality of included trials. The electrical characteristics of stimulation were summarised to allow for comparison across studies. In addition, the surface electromyography (EMG) recording methods were evaluated.ResultsA total of 3753 articles were initially screened, of which 25 met the criteria for inclusion. Studies were divided into those using tSCS for neurophysiological investigations of reflex responses (n = 9) and therapeutic investigations of motor recovery (n = 16). The overall quality of evidence was deemed to be poor-to-fair (10.5 ± 4.9) based on the Downs and Black Quality Checklist criteria. The electrical characteristics were collated to establish the dosage range across stimulation trials. The methods employed by included studies relating to stimulation parameters and outcome measurement varied extensively, although some trends are beginning to appear in relation to electrode configuration and EMG outcomes.ConclusionThis review outlines the parameters currently employed for tSCS of the cervicothoracic and thoracolumbar regions to produce motor responses. However, to establish standardised procedures for neurophysiological assessments and therapeutic investigations of tSCS, further high-quality investigations are required, ideally utilizing consistent electrophysiological recording methods, and reporting common characteristics of the electrical stimulation administered.
| S-EPMC8601579 | biostudies-literature