Alleviation of chronic pain following rat spinal cord compression injury with multimodal actions of huperzine A.
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ABSTRACT:
SUBMITTER: Yu D
PROVIDER: S-EPMC3581914 | biostudies-other | 2013 Feb
REPOSITORIES: biostudies-other
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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:The number of elderly patients with spinal cord injury without radiographic abnormalities (SCIWORA) has been increasing in recent years and common of most cervical spinal cord injuries. Basic research has shown the effectiveness of early decompression after spinal cord injury on the spinal cord without stenosis; no studies have reported the efficacy of decompression in models with spinal cord compressive lesions. The purpose of this study was to evaluate the effects of decompression surgery after acute spinal cord injury in rats with chronic spinal cord compressive lesions, mimicking SCIWORA. A water-absorbent polymer sheet (Aquaprene DX, Sanyo Chemical Industries) was inserted dorsally into the 4-5th cervical sublaminar space in 8-week-old Sprague Dawley rats to create a rat model with a chronic spinal compressive lesion. At the age of 16 weeks, 30 mildly myelopathic or asymptomatic rats with a Basso, Beattie, and Bresnahan score (BBB score) of 19 or higher were subjected to spinal cord compression injuries. The rats were divided into three groups: an immediate decompression group (decompress immediately after injury), a sub-acute decompression group (decompress 1 week after injury), and a non-decompression group. Behavioral and histological evaluations were performed 4 weeks after the injury. At 20 weeks of age, the BBB score and FLS (Forelimb Locomotor Scale) of both the immediate and the sub-acute decompression groups were significantly higher than those of the non-decompression group. There was no significant difference between the immediate decompression group and the sub-acute decompression group. TUNEL (transferase-mediated dUTP nick end labeling) staining showed significantly fewer positive cells in both decompression groups compared to the non-decompression group. LFB (Luxol fast blue) staining showed significantly more demyelination, and GAP-43 (growth associated protein-43) staining tended to show fewer positive cells in the non-decompression group. Decompression surgery in the acute or sub-acute phase of injury is effective after mild spinal cord injury in rats with chronic compressive lesions. There was no significant difference between the immediate decompression and sub-acute decompression groups.
| S-EPMC9402533 | biostudies-literature
Project description:Compression spinal cord injuries are a common cause of morbidity in people who experience a spinal cord injury (SCI). Either as a by-product of a traumatic injury or due to nontraumatic conditions such as cervical myelitis, compression injuries are growing in prevalence clinically and many attempts of animal replication have been described within the literature. These models, however, often focus on the traumatic side of injury or mimic short-term injuries that are not representative of the majority of compression SCI. Of this, nontraumatic spinal cord injuries are severely understudied and have an increased prevalence in elderly populations, adults, and children. Therefore, there is a need to critically evaluate the current animal models of compression SCI and their suitability as a method for clinically relevant data that can help reduce morbidity and mortality of SCI. In this review, we reviewed the established and emerging methods of animal models of compression SCI. These models are the clip, balloon, solid spacer, expanding polymer, remote, weight drop, calibrated forceps, screw, and strap methods. These methods showed that there is a large reliance on the use of laminectomy to induce injury. Furthermore, the age range of many studies does not reflect the elderly and young populations that commonly suffer from compression injuries. It is therefore important to have techniques and methods that are able to minimize secondary effects of the surgeries, and are representative of the clinical cases seen so that treatments and interventions can be developed that are specific.
| S-EPMC9825893 | biostudies-literature
Project description:Spinal cord injury (SCI) typically causes devastating neurological deficits, particularly through damage to fibers descending from the brain to the spinal cord. A major current area of research is focused on the mechanisms of adaptive plasticity that underlie spontaneous or induced functional recovery following SCI. Spontaneous functional recovery is reported to be greater early in life, raising interesting questions about how adaptive plasticity changes as the spinal cord develops. To facilitate investigation of this dynamic, we have developed a SCI model in the neonatal mouse. The model has relevance for pediatric SCI, which is too little studied. Because neural plasticity in the adult involves some of the same mechanisms as neural plasticity in early life(1), this model may potentially have some relevance also for adult SCI. Here we describe the entire procedure for generating a reproducible spinal cord compression (SCC) injury in the neonatal mouse as early as postnatal (P) day 1. SCC is achieved by performing a laminectomy at a given spinal level (here described at thoracic levels 9-11) and then using a modified Yasargil aneurysm mini-clip to rapidly compress and decompress the spinal cord. As previously described, the injured neonatal mice can be tested for behavioral deficits or sacrificed for ex vivo physiological analysis of synaptic connectivity using electrophysiological and high-throughput optical recording techniques(1). Earlier and ongoing studies using behavioral and physiological assessment have demonstrated a dramatic, acute impairment of hindlimb motility followed by a complete functional recovery within 2 weeks, and the first evidence of changes in functional circuitry at the level of identified descending synaptic connections(1).
| S-EPMC4841318 | biostudies-literature
Project description:Approximately one-third of people with a spinal cord injury (SCI) will experience persistent neuropathic pain following injury. This pain negatively affects quality of life and is difficult to treat. Opioids are among the most effective drug treatments, and are commonly prescribed, but experimental evidence suggests that opioid treatment in the acute phase of injury can attenuate recovery of locomotor function. In fact, spinal cord injury and opioid administration share several common features (e.g. central sensitization, excitotoxicity, aberrant glial activation) that have been linked to impaired recovery of function, as well as the development of pain. Despite these effects, the interactions between opioid use and spinal cord injury have not been fully explored. A review of the literature, described here, suggests that caution is warranted when administering opioids after SCI. Opioid administration may synergistically contribute to the pathology of SCI to increase the development of pain, decrease locomotor recovery, and leave individuals at risk for infection. Considering these negative implications, it is important that guidelines are established for the use of opioids following spinal cord and other central nervous system injuries.
| S-EPMC3742731 | biostudies-literature
Project description:BackgroundCentral sensitization is considered a key mechanism underlying neuropathic pain (NP) after spinal cord injury (SCI).MethodsTwo novel proxies for central sensitization were investigated in thoracic SCI subjects with (SCI-NP) and without NP (SCI-nonNP) compared to healthy controls (HC). Specifically, temporal summation of pain (TSP) was investigated by examining pain ratings during a 2-min tonic heat application to the volar forearm. Additionally, palmar heat-induced sympathetic skin responses (SSR) were recorded in order to reveal changes in pain-autonomic interaction above the lesion level. Pain extent was assessed as the percentage of the body area and the number of body regions being affected by NP.ResultsEnhanced TSP was observed in SCI-NP (+66%) compared to SCI-nonNP (-75%, p = 0.009) and HC (-59%, p = 0.021). In contrast, no group differences were found (p = 0.685) for SSR habituation. However, pain extent in SCI-NP was positively correlated with deficient SSR habituation (body area: r = 0.561, p = 0.024; body regions: r = 0.564, p = 0.023).ConclusionsThese results support the value of TSP and heat-induced SSRs as proxies for central sensitization in widespread neuropathic pain syndromes after SCI. Measures of pain-autonomic interaction emerged as a promising tool for the objective investigation of sensitized neuronal states in chronic pain conditions.SignificanceWe present two surrogate readouts for central sensitization in neuropathic pain following SCI. On the one hand, temporal summation of tonic heat pain is enhanced in subjects with neuropathic pain. On the other hand, pain-autonomic interaction reveals potential advanced measures in chronic pain, as subjects with a high extent of neuropathic pain showed diminished habituation of pain-induced sympathetic measures. A possible implication for clinical practice is constituted by an improved assessment of neuronal hyperexcitability potentially enabling mechanism-based treatment.
| S-EPMC9826442 | biostudies-literature
Project description:ContextNeuropathic pain is a common and debilitating condition following SCI. While treatments for neuropathic pain intensity have been reviewed, the impact on pain interference has not been summarized.ObjectiveTo systematically review the effect of neuropathic pain interventions on pain interference in individuals with spinal cord injury.MethodsThis systematic review included randomized controlled trials and quasi-experimental (non-randomized) studies which assessed the impact of an intervention on pain interference in individuals with spinal cord injury and neuropathic pain. Articles were identified by searching MEDLINE (1996 to April 11, 2022), EMBASE (1996 to April 11, 2022), PsycInfo (1987 to April, week 2, 2022). Studies were assessed for methodologic quality using a modified GRADE approach and were given quality of evidence (QOE) scores on a 4-point scale ranging from very low to high.ResultsTwenty studies met the inclusion criteria. These studies fell into the following categories: anticonvulsants (n = 2), antidepressants (n = 1), analgesics (n = 1), antispasmodics (n = 1), acupuncture (n = 2), transcranial direct current stimulation (n = 1), active cranial electrotherapy stimulation (n = 2), transcutaneous electrical nerve stimulation (n = 2), repetitive transcranial magnetic stimulation (n = 1), functional electrical stimulation (n = 1), meditation and imagery (n = 1), self-hypnosis and biofeedback (n = 1), and interdisciplinary pain programs (n = 4).ConclusionWhen considering studies of moderate to high quality, pregabalin, gabapentin, intrathecal baclofen, transcranial direct current stimulation, and transcutaneous electrical nerve stimulation (in 1 of 2 studies) were shown to have beneficial effects on pain interference. However, due to the low number of high-quality studies further research is required to confirm the efficacy of these interventions prior to recommending their use to reduce pain interference.
| S-EPMC11218591 | biostudies-literature
Project description:It is well known spinal cord injury (SCI) can cause chronic neuropathic pain (NP); however its underlying molecular mechanisms remain elusive. This study aimed to disclose differentially expressed genes (DEGs) and activated signaling pathways in association with SCI induced chronic NP, in order to identify its diagnostic and therapeutic targets. Microarray dataset GSE5296 has been downloaded from Gene Expression Omnibus (GEO) database. Significant analysis of microarray (SAM), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and pathway network analysis have been used to compare changes of DEGs and signaling pathways between the SCI and sham-injury group. As a result, DEGs analysis showed there were 592 DEGs with significantly altered expression; among them Ccl3 expression showed the highest upregulation which implicated its association with SCI induced chronic NP. Moreover, KEGG analysis found 209 pathways changed significantly; among them the most significantly activated one is MAPK signaling pathway, which is in line with KEGG analysis results. Our results show Ccl3 is highly associated with SCI induced chronic NP; as the exosomes with Ccl3 can be easily and efficiently detected in peripheral blood, Ccl3 may serve as a potential prognostic target for the diagnosis and treatment of SCI induced chronic NP.
| S-EPMC5661087 | biostudies-literature
Project description:Recovering upper-limb motor function has important implications for improving independence of patients with tetraplegia after traumatic spinal cord injury (SCI).To evaluate the feasibility, safety and effectiveness of robotic-assisted training of upper limb in a chronic SCI population.A total of 10 chronic tetraplegic SCI patients (C4 to C6 level of injury, American Spinal Injury Association Impairment Scale, A to D) participated in a 6-week wrist-robot training protocol (1 hour/day 3 times/week). The following outcome measures were recorded at baseline and after the robotic training: a) motor performance, assessed by robot-measured kinematics, b) corticospinal excitability measured by transcranial magnetic stimulation (TMS), and c) changes in clinical scales: motor strength (Upper extremity motor score), pain level (Visual Analog Scale) and spasticity (Modified Ashworth scale).No adverse effects were observed during or after the robotic training. Statistically significant improvements were found in motor performance kinematics: aim (pre 1.17 ± 0.11 raduans, post 1.03 ± 0.08 raduans, p = 0.03) and smoothness of movement (pre 0.26 ± 0.03, post 0.31 ± 0.02, p = 0.03). These changes were not accompanied by changes in upper-extremity muscle strength or corticospinal excitability. No changes in pain or spasticity were found.Robotic-assisted training of the upper limb over six weeks is a feasible and safe intervention that can enhance movement kinematics without negatively affecting pain or spasticity in chronic SCI. In addition, robot-assisted devices are an excellent tool to quantify motor performance (kinematics) and can be used to sensitively measure changes after a given rehabilitative intervention.
| S-EPMC4519228 | biostudies-literature
Project description:This research evaluates the feasibility of a multimodal pain assessment protocol during rehabilitation following spinal cord injury (SCI). The protocol amalgamates clinical workup (CW), quantitative sensory testing (QST), and psychosocial factors (PSF) administered at 4 (T1), 12 (T2), and 24 (T3) weeks post injury and at discharge (T4). Molecular blood biomarkers (BB) were evaluated via gene expression and proteomic assays at T1 and T4. Different pain trajectories and temporal changes were identified using QST, with inflammation and pain-related biomarkers recorded. Higher concentrations of osteopontin and cystatin-C were found in SCI patients compared to healthy controls, indicating their potential as biomarkers. We observed altered inflammatory responses and a slight increase in ICAM-1 and CCL3 were noted, pointing towards changes in cellular adhesion linked with spinal injury and a possible connection with neuropathic pain. Despite a small patient sample hindering the correlation of feasibility data, descriptive statistical analyses were conducted on stress, depression, anxiety, quality of life, and pain interferences. The SCI Pain Instrument (SCIPI) was efficient in distinguishing between nociceptive and neuropathic pain, showing a progressive increase in severity over time. The findings emphasize the need for the careful consideration of recruitment setting and protocol adjustments to enhance the feasibility of multimodal pain evaluation studies post SCI. They also shed light on potential early adaptive mechanisms in SCI pathophysiology, warranting the further exploration of prognostic and preventive strategies for chronic pain in the SCI population.
| S-EPMC10341965 | biostudies-literature