Inhibition of autotaxin activity ameliorates neuropathic pain derived from lumbar spinal canal stenosis.
Ontology highlight
ABSTRACT:
SUBMITTER: Uranbileg B
PROVIDER: S-EPMC7889906 | biostudies-literature | 2021 Feb
REPOSITORIES: biostudies-literature
Publications
Inhibition of autotaxin activity ameliorates neuropathic pain derived from lumbar spinal canal stenosis.
Uranbileg Baasanjav B Ito Nobuko N Kurano Makoto M Kano Kuniyuki K Uchida Kanji K Sumitani Masahiko M Aoki Junken J Yatomi Yutaka Y
Scientific reports 20210217 1
Lumbar spinal canal stenosis (LSS) or mechanical compression of dorsal root ganglion (DRG) is one of the causes of low back pain and neuropathic pain (NP). Lysophosphatidic acid (LPA) is a potent bioactive lipid mediator that is produced mainly from lysophosphatidylcholine (LPC) via autotaxin (ATX) and is known to induce NP via LPA<sub>1</sub> receptor signaling in mice. Recently, we demonstrated that LPC and LPA were higher in cerebrospinal fluid (CSF) of patients with LSS. Based on the possibl ...[more]
Similar Datasets
Project description:BackgroundChronic persistent low back and lower extremity pain secondary to central spinal stenosis is common and disabling. Lumbar surgical interventions with decompression or fusion are most commonly performed to manage severe spinal stenosis. However, epidural injections are also frequently performed in managing central spinal stenosis. After failure of epidural steroid injections, the next sequential step is percutaneous adhesiolysis and hypertonic saline neurolysis with a targeted delivery. The literature on the effectiveness of percutaneous adhesiolysis in managing central spinal stenosis after failure of epidural injections has not been widely studied.Study designA prospective evaluation.SettingAn interventional pain management practice, a specialty referral center, a private practice setting in the United States.ObjectiveTo evaluate the effectiveness of percutaneous epidural adhesiolysis in patients with chronic low back and lower extremity pain with lumbar central spinal stenosis.MethodsSeventy patients were recruited. The initial phase of the study was randomized, double-blind with a comparison of percutaneous adhesiolysis with caudal epidural injections. The 25 patients from the adhesiolysis group continued with follow-up, along with 45 additional patients, leading to a total of 70 patients. All patients received percutaneous adhesiolysis and appropriate placement of the Racz catheter, followed by an injection of 5 mL of 2% preservative-free lidocaine with subsequent monitoring in the recovery room. In the recovery room, each patient also received 6 mL of 10% hypertonic sodium chloride solution, and 6 mg of non-particulate betamethasone, followed by an injection of 1 mL of sodium chloride solution and removal of the catheter.Outcomes assessmentMultiple outcome measures were utilized including the Numeric Rating Scale (NRS), the Oswestry Disability Index 2.0 (ODI), employment status, and opioid intake with assessment at 3, 6, and 12, 18 and 24 months post treatment. The primary outcome measure was 50% or more improvement in pain scores and ODI scores.ResultsOverall, a primary outcome or significant pain relief and functional status improvement of 50% or more was seen in 71% of patients at the end of 2 years. The overall number of procedures over a period of 2 years were 5.7 ± 2.73.LimitationsThe lack of a control group and a prospective design.ConclusionsSignificant relief and functional status improvement as seen in 71% of the 70 patients with percutaneous adhesiolysis utilizing local anesthetic steroids and hypertonic sodium chloride solution may be an effective management strategy in patients with chronic function limiting low back and lower extremity pain with central spinal stenosis after failure of conservatie management and fluoroscopically directed epidural injections.
| S-EPMC3534877 | biostudies-literature
Project description:The aim of the study was to compare outcome of surgery in patients with lumbar canal stenosis (LCS) based on magnetic resonance imaging (MRI) morphology. This was a prospective study of 96 consecutive patients who underwent surgery at 143 levels of LCS (from L3-L4 to L5-S1). Using patterns on T2 axial MRI, the type of stenosis was determined for each patient. The Swiss Spinal Stenosis Score (SSS) was used to evaluate patients' functionality and outcomes. The definition of treatment success was based on the criteria developed by Stucki et al. Demographic characteristics and post-operative outcomes were compared between trefoil, triangular, and pin-hole groups. Finally, correlation between SSS score and the MRI morphology was assessed. The mean age of patients was 58.4 (SD = 8.9) years. Post-treatment satisfaction was observed in a large portion of the patients (87.5%). The trefoil group (n = 44), triangular group (n = 38), and pin-hole group (n = 14) had similar pre-operative Swiss Spinal Stenosis Score and were not significantly different in age, operative time, blood loss, duration of symptoms, walking distance, symptom severity and physical function (all p>0.4). No correlation between SSS score and the MRI morphology was observed. The findings suggest that the type of stenosis based on magnetic resonance imaging morphology is not indicative of surgical outcome among lumbar canal stenosis patients who undergo surgery at 1-year follow-up.
| S-EPMC4917101 | biostudies-literature
Project description:Lumbar spinal canal stenosis (LSS) is a common spinal disorder among older people. Some LSS patients say that their pain worsens when they lift heavy objects. The Valsalva maneuver is the optimal breathing pattern for producing maximal force. Herein, we present two cases of LSS where the movement of the cauda equina was observed during the Valsalva maneuver.Case Summary:Case 1: A 74-year-old female with a history of LSS presented to our Department of Urology with frequent urination. The patient was diagnosed as having uterine and bladder prolapse. Pelvic cine MRI scan was conducted for detailed evaluation. While the Valsalva maneuver was performed to diagnose pelvic organ prolapses, we observed movement of the cauda equina. Spine MRI and CT, performed one year before presentation, showed severe LSS due to degenerative spondylolisthesis.Case 2: A 73-year-old male underwent radical prostatectomy for prostate cancer. A follow-up cine MRI to confirm urethrorrhea showed the cauda equina moving during the Valsalva maneuver. Moderate LSS due to degenerative spondylolisthesis was retrospectively found on abdominal CT performed before prostatectomy.Conclusion: The findings of our report suggest that movement of the cauda equina during the Valsalva maneuver may be implicated in LSS.
| S-EPMC9493334 | biostudies-literature
Project description:IntroductionIn Japan, conservative therapy for patients with lumbar spinal stenosis (LSS) includes non-steroidal anti-inflammatory drugs (NSAIDs), prostaglandin E1, tramadol, physical/exercise therapy, and nerve blocks. Mirogabalin, a selective oral α2δ ligand, is approved for treating peripheral neuropathic pain, though data regarding visual analog scores (VAS) for pain in patients with LSS are limited. We investigated the efficacy and safety of mirogabalin as an add-on treatment in patients with LSS taking NSAIDs compared with patients taking NSAIDs only.MethodsThis multicenter, randomized, open-label study (MiroTAS) was conducted at 32 centers in Japan between June 2020 and October 2021. Patients were randomly assigned to mirogabalin and NSAIDs or NSAIDs alone in a 1:1 ratio. NSAIDs were administered according to their Japanese package inserts; mirogabalin was administered based on renal function [creatinine clearance (CrCL) ≥ 60 mL/min, 5 mg twice daily (BID) in Weeks 1-2, 10 mg BID in Weeks 3-4, and 15 or 10 mg BID after Week 5; CrCL 30 to < 60 mL/min, 2.5 mg BID Weeks 1-2, 5 mg BID Weeks 3-4, and 7.5 or 5 mg BID after Week 5]. The primary endpoint was the change in VAS score for leg pain from baseline to Week 12. Secondary endpoints were quality of life, evaluated using the EuroQol five-dimensional descriptive system (EQ-5D-5L) (at baseline and Week 12) and Patient Global Impression of Change (PGIC) (at Week 12), and safety. Change in VAS score at Week 12 was calculated using a linear mixed model for repeated measures. The safety endpoints were treatment-emergent adverse events (TEAEs) and adverse drug reactions.ResultsIn total, 220 patients who met the eligibility criteria were enrolled. In the mirogabalin and NSAIDs and NSAIDs groups, mean ages (67.8 vs. 70.9 years), proportions of female patients (54.5% vs. 49.0%), mean body weights (63.9 vs. 62.0 kg), mean CrCL values (81.5 vs. 70.7 mL/min), proportions of patients with CrCL 30 to < 60 mL/min (27.3% vs. 33.7%), mean VAS scores (63.8 vs. 62.8 mm), and proportions of patients with VAS score ≥ 60 (53.6% vs. 52.9%) at enrollment were similar. The median durations of LSS were 9.0 and 11.0 months and the spine pain DETECT questionnaire (SPDQ) scores were 6.8 and 7.8, respectively. The least square (LS) mean change in VAS score from baseline to Week 12 was - 24.1 mm in the mirogabalin and NSAIDs group and - 14.2 mm in the NSAIDs group (both P < 0.0001 vs. baseline). The difference in LS mean was - 9.9 [95% confidence interval (CI), - 18.0, - 1.8] (P = 0.0174). The improvement in EQ-5D-5L score at Week 12 was significantly greater in the mirogabalin and NSAIDs group versus the NSAIDs group [mean difference, 0.0529 (95% CI, 0.0036, 0.1022), P = 0.0357]. At Week 12, the proportions of patients with PGIC scores ≤ 3 and ≤ 2 were higher in the mirogabalin and NSAIDs group vs. the NSAIDs group (76.2% vs. 50.0%, P = 0.0006, and 47.6% vs. 32.4%, P = 0.0523). In the mirogabalin and NSAIDs group, the incidences of TEAEs and adverse drug reactions were 60.9% and 57.3%, respectively, and the most common TEAEs were somnolence (30.0%) and dizziness (25.5%).ConclusionsThe addition of mirogabalin to NSAIDs improved VAS, EQ-5D-5L, and PGIC. The main TEAEs were somnolence and dizziness. The addition of mirogabalin to NSAIDs improved peripheral neuropathic pain associated with LSS and raised no new safety concerns.Trial registrationJapan Registry of Clinical Trials (jRCTs021200007).
| S-EPMC9298169 | biostudies-literature
Project description:Lumbar spinal stenosis (LSS) affects more than 200,000 adults in the United States, resulting in substantial pain and disability. It is the most common reason for spinal surgery in patients over 65 years. Lumbar spinal stenosis is a clinical syndrome of pain in the buttocks or lower extremities, with or without back pain. It is associated with reduced space available for the neural and vascular elements of the lumbar spine. The condition is often exacerbated by standing, walking, or lumbar extension and relieved by forward flexion, sitting, or recumbency. Clinical care and research into lumbar spinal stenosis is complicated by the heterogeneity of the condition, the lack of standard criteria for diagnosis and inclusion in studies, and high rates of anatomic stenosis on imaging studies in older people who are completely asymptomatic. The options for non-surgical management include drugs, physiotherapy, spinal injections, lifestyle modification, and multidisciplinary rehabilitation. However, few high quality randomized trials have looked at conservative management. A systematic review concluded that there is insufficient evidence to recommend any specific type of non-surgical treatment. Several different surgical procedures are used to treat patients who do not improve with non-operative therapies. Given that rapid deterioration is rare and that symptoms often wax and wane or gradually improve, surgery is almost always elective and considered only if sufficiently bothersome symptoms persist despite trials of less invasive interventions. Outcomes (leg pain and disability) seem to be better for surgery than for non-operative treatment, but the evidence is heterogeneous and often of limited quality.
| S-EPMC6887476 | biostudies-literature
Project description:The objective of this study was to evaluate the efficacy of a microendoscopic spinal decompression surgical technique using a novel approach for the treatment of lumbar spinal canal stenosis (LSCS). The following modifications were made to the conventional microendoscopic bilateral decompression via the unilateral approach: the base of the spinous process was first resected partially to secure a working space, so as not to separate the spinous process from the lamina. The tip of the tubular retractor was placed at the midline of the lamina, where laminectomy was performed microendoscopically. A total of 126 stenotic levels were decompressed in 70 patients. The mean operating time per level was 77.0 minutes, and the mean intraoperative blood loss per level was 15.0 mL. There were no dural tears or neurological injuries intraoperatively. Fracture of the spinous process was detected postoperatively in two patients, both of whom were asymptomatic. All patients could be followed up for at least 12 months. Their median Japanese Orthopaedic Association (JOA) score improved significantly from 16 points preoperatively to 27.5 points after the surgery (p < 0.001). The case series showed that the modifications of the technique improved the safety and ease of performance of the microendoscopic decompression surgery for LSCS.
| S-EPMC3864472 | biostudies-other
Project description:To investigate the role of DNA methylation in modulating chronic neuropathic pain (NPP), and identify possible target genes of DNA methylation involved in this process. The chronic constriction injury (CCI) induced NPP model was used. The Arraystar Rat RefSeq Promoter Arrays were used to identify the methylation profiles at the genome-wide level in the DNA promoter regions of the lumbar spinal cord in rats 14 Days following CCI surgery. The underlying genes with differential methylation were then identified and submitted to Gene Ontology and pathway analysis. Methyl-DNA immunoprecipitation quantitative PCR (MeDIP-qPCR) and quantitative reverse transcription-PCR (RT‒qPCR) were used to confirm gene methylation and expression.
2022-12-07 | GSE219038 | GEO
Project description:BackgroundThe accurate preoperative identification of decompression levels is crucial for the success of surgery in patients with multi-level lumbar spinal stenosis (LSS). The objective of this study was to develop machine learning (ML) classifiers that can predict decompression levels using computed tomography myelography (CTM) data from LSS patients.MethodsA total of 1095 lumbar levels from 219 patients were included in this study. The bony spinal canal in CTM images was manually delineated, and radiomic features were extracted. The extracted data were randomly divided into training and testing datasets (8:2). Six feature selection methods combined with 12 ML algorithms were employed, resulting in a total of 72 ML classifiers. The main evaluation indicator for all classifiers was the area under the curve of the receiver operating characteristic (ROC-AUC), with the precision-recall AUC (PR-AUC) serving as the secondary indicator. The prediction outcome of ML classifiers was decompression level or not.ResultsThe embedding linear support vector (embeddingLSVC) was the optimal feature selection method. The feature importance analysis revealed the top 5 important features of the 15 radiomic predictors, which included 2 texture features, 2 first-order intensity features, and 1 shape feature. Except for shape features, these features might be eye-discernible but hardly quantified. The top two ML classifiers were embeddingLSVC combined with support vector machine (EmbeddingLSVC_SVM) and embeddingLSVC combined with gradient boosting (EmbeddingLSVC_GradientBoost). These classifiers achieved ROC-AUCs over 0.90 and PR-AUCs over 0.80 in independent testing among the 72 classifiers. Further comparisons indicated that EmbeddingLSVC_SVM appeared to be the optimal classifier, demonstrating superior discrimination ability, slight advantages in the Brier scores on the calibration curve, and Net benefits on the Decision Curve Analysis.ConclusionsML successfully extracted valuable and interpretable radiomic features from the spinal canal using CTM images, and accurately predicted decompression levels for LSS patients. The EmbeddingLSVC_SVM classifier has the potential to assist surgical decision making in clinical practice, as it showed high discrimination, advantageous calibration, and competitive utility in selecting decompression levels in LSS patients using canal radiomic features from CTM.
| S-EPMC10795799 | biostudies-literature
Project description:Purpose:To develop a self-administered diagnostic screening questionnaire for lumbar spinal stenosis (LSS) consisting of items with high content validity and to investigate the diagnostic value of the questionnaire and the items. Patients and Methods:A self-reported diagnostic LSS screening questionnaire was developed based on items from the existing literature describing key symptoms of LSS. The screening questionnaire (index test) was to be tested in a cohort of patients with persistent lumbar and/or leg pain recruited from a Danish publicly funded outpatient secondary care spine clinic with clinicians performing the reference test. However, to avoid unnecessary collection of data if the screening questionnaire proved to be of limited value, a case-control design was incorporated into the cohort design including an interim analysis. Additional cases for the case-control study were recruited at two Danish publicly funded spine surgery departments. Prevalence, sensitivity, specificity and diagnostic odds ratio (OR) were calculated for each individual item, and AUC (area under the curve) was calculated to examine the performance of the full questionnaire. Results:A 13-item Danish questionnaire was developed and tested in 153 cases and 230 controls. The interim analysis was not in favour of continuing the cohort study, and therefore, only results from the case-control study are reported. There was a positive association for all items except the presence of back pain. However, the association was only moderate with ORs up to 3.3. When testing the performance of the whole questionnaire, an AUC of 0.72 was reached with a specificity of 20% for a fixed sensitivity of 95%. Conclusion:The items were associated with LSS and therefore have some potential to identify LSS patients. However, the association was not strong enough to provide sufficient accuracy for a diagnostic tool. Additional dimensions of symptoms of LSS need identification to obtain a reliable questionnaire for screening purposes.
| S-EPMC7450213 | biostudies-literature
Project description:BackgroundThe spinal phosphodiesterase-4 (PDE4) plays an important role in chronic pain. Inhibition of PDE4, an enzyme catalyzing the hydrolysis of cyclic adenosine monophosphate AMP (cAMP), produces potent antinociceptive activity. However, the antinociceptive mechanism remains largely unknown. Connexin43 (Cx43), a gap junction protein, has been shown to be involved in controlling pain transduction at the spinal level; restoration of Cx43 expression in spinal astrocytes to the normal levels reduces nerve injury-induced pain. Here, we evaluate the novel mechanisms involving spinal cAMP-Cx43 signaling by which PDE4 inhibitors produce antinociceptive activity.MethodsFirst, we determined the effect of PDE4 inhibitors rolipram and roflumilast on partial sciatic nerve ligation (PSNL)-induced mechanical hypersensitivity. Next, we observed the role of cAMP-Cx43 signaling in the effect of PDE4 inhibitors on PSNL-induced mechanical hypersensitivity.ResultsSingle or repeated, intraperitoneal or intrathecal administration of rolipram or roflumilast significantly reduced mechanical hypersensitivity in mice following PSNL. In addition, repeated intrathecal treatment with either of PDE4 inhibitors reduced PSNL-induced downregulation of cAMP and Cx43, and upregulation of proinflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-1β. Furthermore, the antinociceptive effects of PDE4 inhibitors were attenuated by the protein kinase A (PKA) inhibitor H89, TNF-α, or Cx43 antagonist carbenoxolone. Finally, PSNL-induced upregulation of PDE4B and PDE4D, especially the PDE4B subtype, was reduced by treatment with either of the PDE4 inhibitors.ConclusionsThe results suggest that the antinociceptive effect of PDE4 inhibitors is contributed by increasing Cx43 expression via cAMP-PKA-cytokine signaling in the spinal dorsal horn.
| S-EPMC8981432 | biostudies-literature