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Molecular Pain 2021Chronic neuropathic pain is a debilitating ordeal for patients worldwide and pharmacological treatment efficacy is still limited. As many pharmacological interventions...
Chronic neuropathic pain is a debilitating ordeal for patients worldwide and pharmacological treatment efficacy is still limited. As many pharmacological interventions for neuropathic pain often fail, insights into the underlying mechanism and role of identified receptors is of utmost importance. An important target for improving treatment of neuropathic pain is the descending serotonergic system as these projections modulate nociceptive signaling in the dorsal horn. Also with use of last resort treatments like spinal cord stimulation (SCS), the descending serotonergic projections are known to be involved in the pain relieving effect. This systematic review summarizes the involvement of the serotonergic system on nociceptive modulation in the healthy adult rodent and the chronic neuropathic rodent and summarizes all available literature on the serotonergic system in the SCS-treated neuropathic rodent. Medline, Embase and Pubmed databases were used in the search for articles. Descending serotonergic modulation of nociceptive signaling in spinal dorsal horn in normal adult rat is mainly inhibitory and mediated by 5-HT1a, 5-HT1b, 5-HT2c, 5-HT3 and 5-HT4 receptors. Upon injury and in the neuropathic rat, this descending serotonergic modulation becomes facilitatory via activation of the 5-HT2a, 5-HT2b and 5-HT3 receptors. Analgesia due to neuromodulatory intervention like SCS restores the inhibitory function of the descending serotonergic system and involves 5-HT2, 5-HT3 and 5-HT4 receptors. The results of this systematic review provide insights and suggestions for further pharmacological and or neuromodulatory treatment of neuropathic pain based on targeting selected serotonergic receptors related to descending modulation of nociceptive signaling in spinal dorsal horn. With the novel developed SCS paradigms, the descending serotonergic system will be an important target for mechanism-based stimulation induced analgesia.
Topics: Animals; Humans; Neuralgia; Nociception; Rats; Receptors, Serotonin, 5-HT3; Spinal Cord; Spinal Cord Dorsal Horn; Spinal Cord Stimulation
PubMed: 34662215
DOI: 10.1177/17448069211043965 -
Spine Oct 2010Systematic review. (Review)
Review
STUDY DESIGN
Systematic review.
OBJECTIVE
To define the optimal time for initiation of rehabilitation and review the most clinically relevant outcome measures of upper and lower limb motor function of the rehabilitating spinal cord injured patient, using a systematic review and expert opinion.
SUMMARY OF BACKGROUND DATA
Comprehensive rehabilitation programs are required for patients after spinal cord injury (SCI) as early as feasible. In a dedicated SCI rehabilitation setting, effective treatment and proper monitoring of spontaneous and rehabilitation-based motor function improvements by means of appropriate, valid, reliable and internationally accepted clinical assessment tools is warranted.
METHODS
Focused questions on key topics in rehabilitation of the spinal cord injured patient were defined by a panel of spine trauma surgeons. A keyword literature search for pertinent articles was conducted using multiple databases. Suitable articles were screened and the quality of evidence was graded and tabulated. Based on the evidence and expert opinion, recommendations were composed and rated as strong or weak.
RESULTS
The outcome measures literature search yielded a total of 1251 abstracts. Out of these 86 articles were studied in detail. One high quality study was found with 3 articles referring to it. Furthermore, there were 19 moderate quality studies, 39 low quality studies, and 25 very low quality studies. The timing literature search yielded 508 abstracts of which 3 articles focused on the question and were all graded as low quality.
CONCLUSION
For general motor function, assessing the American Spinal Injury Association motor score and the Spinal Cord Independence Measure III is strongly recommended. The American Spinal Injury Association motor score is also useful in assessing upper- and lower-extremity motor function. For ambulatory function, a timed walk test like the 10 m Walk test in combination with the Walking Index for SCI II is strongly recommended. Early rehabilitation, defined as within 30 days of injury, improves outcome and recovery for spinal cord trauma patients.
Topics: Disability Evaluation; Exercise Test; Humans; Motor Activity; Neurologic Examination; Recovery of Function; Rehabilitation Centers; Severity of Illness Index; Spinal Cord Injuries; Spinal Injuries; Time Factors; Treatment Outcome; Walking
PubMed: 20881469
DOI: 10.1097/BRS.0b013e3181f1a979 -
PloS One 2023We performed a systematic review and meta-analysis on the incidence of secondary tethered spinal cord (TSC) between prenatal and postnatal closure in patients with MMC.... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
We performed a systematic review and meta-analysis on the incidence of secondary tethered spinal cord (TSC) between prenatal and postnatal closure in patients with MMC. The objectives was to understand the incidence of secondary TSC after prenatal surgery for MMC compared to postnatal surgery for MMC.
MATERIAL AND METHODS
On May 4, 2023, a systematic search was conducted in Medline, Embase, and the Cochrane Library to gather relevant data. Primary studies focusing on repair type, lesion level, and TSC were included, while non-English or non-Dutch reports, case reports, conference abstracts, editorials, letters, comments, and animal studies were excluded. Two reviewers assessed the included studies for bias risk, following PRISMA guidelines. TSC frequency in MMC closure types was determined, and the relationship between TSC occurrence and closure technique was analyzed using relative risk and Fisher's exact test. Subgroup analysis revealed relative risk differences based on study designs and follow-up periods. A total of ten studies, involving 2,724 patients, were assessed. Among them, 2,293 patients underwent postnatal closure, while 431 received prenatal closure for the MMC defect. In the prenatal closure group, TSC occurred in 21.6% (n = 93), compared to 18.8% (n = 432) in the postnatal closure group. The relative risk (RR) of TSC in patients with prenatal MMC closure versus postnatal MMC closure was 1.145 (95%CI 0.939 to 1.398). Fisher's exact test indicated a statistically non-significant association (p = 0.106) between TSC and closure technique. When considering only RCT and controlled cohort studies, the overall RR for TSC was 1.308 (95%CI 1.007 to 1.698) with a non-significant association (p = .053). For studies focusing on children up until early puberty (maximum 12 years follow-up), the RR for tethering was 1.104 (95%CI 0.876 to 1.391), with a non-significant association (p = 0.409).
CONCLUSION AND DISCUSSION
This review found no significant increase in relative risk of TSC between prenatal and postnatal closure in MMC patients, but a trend of increased TSC in the prenatal group. More long-term data on TSC after fetal closure is needed for better counseling and outcomes in MMC.
Topics: Humans; Female; Pregnancy; Meningomyelocele; Fetus; Neurosurgical Procedures; Incidence; Spinal Cord
PubMed: 37379312
DOI: 10.1371/journal.pone.0287175 -
Journal of Neurosurgical Sciences Feb 2024Spinal cord stimulation (SCS) is a modern neuromodulation technique extensively proven to be an effective modality for treatment of chronic neuropathic pain. It has been... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Spinal cord stimulation (SCS) is a modern neuromodulation technique extensively proven to be an effective modality for treatment of chronic neuropathic pain. It has been mainly studied for complex regional pain syndrome (CRPS) and failed back surgery syndrome (FBSS) and recent data almost uniformly establishes its statistically significant positive therapeutic results. It has also been compared with other available treatment modalities across various studies. However, long term data on maintenance of its efficacious potential remains less explored. Few studies have reported data on long follow-up times (>= 12 months) and have compared its efficacy with other treatment options for chronic pain, respectively. Our study pools and analyzes the available data and compares SCS with other treatment options. It also analyzes the efficacy of SCS in long term management of patients with chronic pain.
EVIDENCE ACQUISITION
We reviewed all the data available on MEDLINE, Embase and Cochrane CENTRAL using a search strategy designed to fit our pre-set inclusion and exclusion criteria. Both single-arm and double-arm studies were included. The primary outcome was defined as decrease of visual analogue scale (VAS) by >50% at 6, 12 and/or 24 months after SCS.
EVIDENCE SYNTHESIS
According to the pooled data of double-arm studies, SCS has unanimously proven its superiority over other treatment options at 6 months follow-up; however it fails to prove statistically significant difference in results at longer treatment intervals. Dorsal root ganglion stimulation, a relatively recent technique with the same underlying physiologic mechanisms as SCS, showed far more promising results than SCS. Single-arm studies show around 70% patients experiencing greater than 50% reduction in their VAS scores at 6 and 12 months.
CONCLUSIONS
SCS is a viable option for management of chronic neuropathic pain secondary to FBSS and CRPS. However, data available for its long term efficacy remains scarce and show no further statistically significant results.
Topics: Humans; Spinal Cord Stimulation; Chronic Pain; Treatment Outcome; Neuralgia; Complex Regional Pain Syndromes; Failed Back Surgery Syndrome; Spinal Cord
PubMed: 36943763
DOI: 10.23736/S0390-5616.23.05930-1 -
Spinal Cord Jun 2021This study is a systematic review. (Review)
Review
STUDY DESIGN
This study is a systematic review.
OBJECTIVES
To evaluate current in vivo techniques used in the investigation of the blood-spinal cord barrier (BSCB).
METHODS
Search of English language literature for animal studies that investigated the BSCB in vivo. Data extraction included animal model/type, protocol for BSCB evaluation, and study outcomes. Descriptive syntheses are provided.
RESULTS
A total of 40 studies were included, which mainly investigated rodent models of experimental autoimmune encephalomyelitis (EAE) or spinal cord injury (SCI). The main techniques used were magnetic resonance imaging (MRI) and intravital microscopy (IVM). MRI served as a reliable tool to longitudinally track BSCB permeability changes with dynamic contrast enhancement (DCE) using gadolinium, or assess inflammatory infiltrations with targeted alternative contrast agents. IVM provided high-resolution visualization of cellular and molecular interactions across the microvasculature, commonly with either epi-fluorescence or two-photon microscopy. MRI and IVM techniques enabled the evaluation of therapeutic interventions and mechanisms that drive spinal cord dysfunction in EAE and SCI. A small number of studies demonstrated the feasibility of DCE-computed tomography, ultrasound, bioluminescent, and fluorescent optical imaging methods to evaluate the BSCB. Technique-specific limitations and multiple protocols for image acquisition and data analyses are described for all techniques.
CONCLUSION
There are few in vivo investigations of the BSCB. Additional studies are needed in less commonly studied spinal cord disorders, and to establish standardized protocols for data acquisition and analysis. Further development of techniques and multimodal approaches could overcome current imaging limitations to the spinal cord. These advancements might promote wider adoption of techniques, and can provide greater potential for clinical translation.
Topics: Animals; Blood-Brain Barrier; Disease Models, Animal; Magnetic Resonance Imaging; Permeability; Spinal Cord; Spinal Cord Injuries
PubMed: 33742118
DOI: 10.1038/s41393-021-00623-7 -
Journal of Voice : Official Journal of... Jul 2021To analyze and assess studies on the topic and to describe the vocal parameters of patients with traumatic spinal cord injury (SCI) based on the literature. (Review)
Review
OBJECTIVE
To analyze and assess studies on the topic and to describe the vocal parameters of patients with traumatic spinal cord injury (SCI) based on the literature.
METHOD
Studies were identified and selected by searching for articles on the subject published in any journal, using pre-established descriptors: "spinal cord injury," "speech," "lang$," "speech-lang$," and "voice" ("traumatismos da medula espinal," "fala," "fona$," "fonoaud$," and "voz" in Brazilian Portuguese). All the phases of the study were conducted independently by the researchers and in the event of disagreement, a final decision was reached by consensus. The articles selected were critically assessed based on their objectives, treatment, and assessment criteria and methods, results and conclusions, as well their level of scientific evidence.
RESULTS
A total of 70 scientific articles were identified, eight of which were considered valid based on the inclusion criteria. Research on the contribution of speech therapy to patients with SCI is scarce, particularly regarding voice assessment and treatment. Descriptive and observational studies predominated, with a small sample. Data collection was predominated cross-sectional, which made it possible to identify evaluation and intervention techniques, but the methodologies described preclude generalizations. The results indicated that the parameters of the respiratory function and vocal production in patients with traumatic SCI were reduced lung capacity, presence of voice problems, presence of perceived voice problems, and altered activation of accessory respiratory muscle.
CONCLUSION
The vocal parameters of the patients with traumatic SCI can be described, considering the lack of information available. Disorders related to speech therapy vary in accordance with the type and level of injury. It is important to increase scientific production in this area, particularly randomized trials, in order to establish assessment criteria and treatment techniques and improve levels of evidence.
Topics: Cross-Sectional Studies; Humans; Speech; Spinal Cord Injuries; Voice; Voice Disorders
PubMed: 31937482
DOI: 10.1016/j.jvoice.2019.12.013 -
World Neurosurgery Jun 2022Numerous preclinical studies have been performed in recent years on the effects of the administration of growth factor gene-modified cells in spinal cord injury (SCI).... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Numerous preclinical studies have been performed in recent years on the effects of the administration of growth factor gene-modified cells in spinal cord injury (SCI). However, findings of these studies are contradictory.
OBJECTIVE
The present study aims to conduct a systematic review and meta-analysis of animal studies evaluating the effects of administration of growth factor gene-modified cells on locomotion recovery after SCI.
METHODS
A search of the MEDLINE, Embase, Scopus, and Web of Science databases was conducted, including all animal studies until the end of 2020. Two researchers screened search results, summarized relevant studies and assessed risk of bias, independently.
RESULTS
Thirty-three studies were included in the final analysis. Transplantation of growth factor gene-modified cells in the injured spinal cord resulted in a significant improvement in locomotion of animals compared with nontreated animals (standardized mean difference = 1.86; 95% confidence interval, 1.39-2.33; P < 0.0001)] and non-genetically modified cell-treated animals (standardized mean difference = 1.30; 95% confidence interval, 0.80-1.79; P < 0.0001). Transplantation efficacy of these cells failed to achieve significance in moderate lesions (P = 0.091), when using modified neural stem/progenitor cells (P = 0.164), when using synthetic neurotrophins (P = 0.086) and when the number of transplanted cells was less than 1.0 × 10 cells per animal (P = 0.119).
CONCLUSIONS
The results showed that transplantation of growth factor gene- modified cells significantly improved locomotion in SCI animal models. However, there is a major concern regarding the safety of transplantation of genetically modified cells, in terms of overexpressing growth factors. Further studies are needed before any effort to perform a translational and clinical study.
Topics: Animals; Humans; Locomotion; Models, Animal; Neural Stem Cells; Recovery of Function; Spinal Cord; Spinal Cord Injuries
PubMed: 35276395
DOI: 10.1016/j.wneu.2022.03.012 -
World Neurosurgery Feb 2016Traumatic spinal cord injury (SCI) is a devastating neurologic entity characterized by a primary insult followed by a secondary pathologic cascade that propagates... (Review)
Review
BACKGROUND
Traumatic spinal cord injury (SCI) is a devastating neurologic entity characterized by a primary insult followed by a secondary pathologic cascade that propagates further injury. Hypothermia has an established clinical role in preventing SCI after cardiac arrest and thoracoabdominal aortic aneurysm repair, yet its emergence as a potential neuroprotectant after spinal cord trauma remains experimental. There are currently no pharmacologic interventions available to prevent secondary mechanisms of injury after spinal cord trauma.
METHODS
Systematic review of literature.
RESULTS
Experimental studies demonstrated that hypothermia diminishes secondary pathomechanisms, such as ischemia, oxidative stress, apoptosis, inflammation, and edema. Early onset and longer durations of hypothermia as well as concomitant steroids or neural stem cell engraftment combined with hypothermia appear to improve functional and histologic outcomes in animal models of spinal cord trauma. Recent clinical studies provide evidence that localized and systemic hypothermia may be applied safely and efficaciously in patients with severe acute SCI. Randomized clinical trials are needed to better evaluate optimal cooling parameters and the effectiveness of hypothermia after traumatic SCI.
CONCLUSION
Although variability exists in the literature, therapeutic hypothermia most likely confers neuroprotection after spinal cord trauma by diminishing the destructive secondary cascade. The available clinical data suggest that regional and systemic hypothermia is a relatively safe and feasible initial treatment modality for patients with acute SCI when combined with surgical decompression/stabilization with or without steroids. However, establishing a clinical role for therapeutic hypothermia after spinal cord trauma will invariably depend on future well-designed, multicentered, randomized, controlled clinical trial data.
Topics: Animals; Humans; Hypothermia, Induced; Spinal Cord Injuries
PubMed: 26433095
DOI: 10.1016/j.wneu.2015.09.079 -
Physical Therapy Jun 2020Pain is one of the main symptoms associated with spinal cord injury (SCI) and can be associated with changes to the central nervous system (CNS). (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pain is one of the main symptoms associated with spinal cord injury (SCI) and can be associated with changes to the central nervous system (CNS).
PURPOSE
This article provides an overview of the evidence relating to CNS changes (structural and functional) associated with pain in SCIs.
DATA SOURCES
A systematic review was performed, according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations, on PubMed, Embase, and Web of Science in March 2018.
STUDY SELECTION
Studies were selected if they concerned changes in the CNS of patients with SCI, regardless of the type of imagery.
DATA EXTRACTION
Data were extracted by 2 blinded reviewers.
DATA SYNTHESIS
There is moderate evidence for impaired electroencephalographic function and metabolic abnormalities in the anterior cingulate in patients experiencing pain. There is preliminary evidence that patients with pain have morphological and functional changes to the somatosensory cortex and alterations to thalamic metabolism. There are conflicting data regarding the relationships between lesion characteristics and pain. In contrast, patients without pain can display protective neuroplasticity.
LIMITATIONS AND CONCLUSION
Further studies are required to elucidate fully the relationships between pain and neuroplasticity in patients with SCIs. However, current evidence might support the use of physical therapist treatments targeting CNS plasticity in patients with SCI pain.
Topics: Adult; Brain; Central Nervous System; Chronic Pain; Electroencephalography; Gyrus Cinguli; Humans; Magnetic Resonance Imaging; Neuralgia; Neuroimaging; Neuronal Plasticity; Selection Bias; Somatosensory Cortex; Spinal Cord; Spinal Cord Injuries; Thalamus
PubMed: 32201890
DOI: 10.1093/ptj/pzaa043 -
International Journal of Molecular... Apr 2019Acute traumatic spinal cord injury (SCI) involves primary and secondary injury mechanisms. The primary mechanism is related to the initial traumatic damage caused by the...
Acute traumatic spinal cord injury (SCI) involves primary and secondary injury mechanisms. The primary mechanism is related to the initial traumatic damage caused by the damaging impact and this damage is irreversible. Secondary mechanisms, which begin as early as a few minutes after the initial trauma, include processes such as spinal cord ischemia, cellular excitotoxicity, ionic dysregulation, and free radical-mediated peroxidation. SCI is featured by different forms of injury, investigating the pathology and degree of clinical diagnosis and treatment strategies, the animal models that have allowed us to better understand this entity and, finally, the role of new diagnostic and prognostic tools such as miRNA could improve our ability to manage this pathological entity. Autopsy could benefit from improvements in miRNA research: the specificity and sensitivity of miRNAs could help physicians in determining the cause of death, besides the time of death.
Topics: Animals; Biomarkers; Disease Management; Disease Models, Animal; Disease Susceptibility; Gene Expression; Humans; MicroRNAs; Multigene Family; Severity of Illness Index; Spinal Cord Injuries
PubMed: 31013946
DOI: 10.3390/ijms20081841