Using MRI data from 30 volunteers spanning four degeneration stages, we developed an image-informed constitutive modeling framework that integrated deep learning-based tissue delineation with biphasic-swelling simulations. The segmentation framework achieved a mean Dice coefficient of 0.93 +/- 0.02. Radiomic descriptors were linked with stage-dependent material properties, including fixed charge density and hydraulic permeability, and the resulting mechanical responses were evaluated under free-swelling, creep, and stress-relaxation. Radiomic-mechanical associations were stage dependent, with the strongest statistically supported association observed in healthy discs between major axis length and equilibrium residual force (rho = 0.85, 95% CI 0.67-0.95, q < 0.001). Equilibration time (tau(95%)) peaked in the moderate degeneration group across all three loading modes, increasing from 2.134 +/- 0.490 h to 6.996 +/- 1.939 h in free-swelling, from 8.018 +/- 1.011 h to 15.105 +/- 3.142 h in creep, and from 0.428 +/- 0.090 h to 1.085 +/- 0.641 h in stress-relaxation, suggesting a transport-limited transitional stage. This research demonstrates a reproducible workflow for linking non-invasive imaging with constitutive modeling to fundamental material laws, providing a quantitative basis for investigating stage-dependent changes in disc mechanics.
In this study, network pharmacology, molecular docking, molecular dynamics simulation, and experimental validation were used to investigate the pharmacological basis and potential molecular mechanisms of Yi Qi Huo Xue Decoction (YQHXD) in lumbar disc degeneration (LDD). A total of 678 active compound-related targets of YQHXD and 296 potential LDD-associated therapeutic targets were identified. Protein-protein interaction network analysis and topological analysis identified several candidate targets, including AKT1, IL6, TNF, BCL2, and STAT3. Enrichment analyses using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes indicated that the candidate targets were linked to functions including protein binding and ATP binding, with pathway enrichment that included PI3K-AKT signaling. Molecular docking predicted interactions between selected active compounds, such as quercetin, Tetraneurin A, and isorhamnetin, and the core targets. Molecular dynamics simulations further suggested that the lowest-energy complexes remained stable. Seventy male Sprague-Dawley rats were randomly assigned to the control, sham-operated, model, positive control, and low-, medium-, and high-dose YQHXD groups. After the establishment of a coccygeal intervertebral disc puncture model in the model, positive control, and YQHXD groups, rats were administered YQHXD or celecoxib by oral gavage for 8 weeks, whereas the control and sham-operated groups received normal saline. Histopathological evaluation showed that YQHXD treatment was associated with reduced intervertebral disc degeneration in this model. Enzyme-linked immunosorbent assay, polymerase chain reaction, and western blot analyses showed changes in the mRNA and protein expression levels of selected targets, including AKT1, BCL2, and STAT3. These findings suggest that YQHXD may exert preclinical protective effects in LDD through multi-component and multi-target regulation involving inflammation- and apoptosis-related mechanisms. This study provides preliminary preclinical evidence supporting further investigation of YQHXD for LDD.
Far-out syndrome associated with lumbosacral transitional vertebrae usually involves extraforaminal entrapment of the L5 nerve root, whereas dual compression of the S1 nerve root is rarely recognized. We report a 50-year-old man with lumbarization of S1 who presented with a two-year history of low back pain and left S1 radiculopathy that worsened despite conservative treatment. Imaging revealed an L5-S1 disc herniation compressing the descending S1 nerve root and S1-S2 extraforaminal stenosis caused by pseudoarthrosis and osteophyte formation. Routine magnetic resonance imaging suggested possible extraforaminal involvement, while sacral plexus magnetic resonance imaging with three-dimensional reconstruction more clearly delineated compression of the exiting S1 nerve root. Selective S1 nerve root blocks performed at the intracanal and extraforaminal levels each produced reproducible but incomplete symptom relief, supporting dual-site compression. Single-stage unilateral biportal endoscopic decompression was performed using interlaminar and paraspinal approaches, achieving decompression at both sites without complications. Radicular symptoms improved immediately after surgery, and sustained clinical improvement was observed at 6 months. This case highlights a diagnostic pitfall in lumbosacral transitional vertebrae, in which concomitant intracanal disease may mask extraforaminal entrapment, and emphasizes the value of targeted imaging and selective nerve root blocks in surgical planning.
IntroductionAging is characterized by gradual structural and functional changes in the body over time, with intervertebral disc degeneration (IVDD) representing a key manifestation of spinal aging and a major contributor to low back pain (LBP).MethodsThis study utilized bioinformatics and machine learning approaches to identify aging-related biomarkers associated with IVDD in whole blood samples. By analyzing GEO datasets alongside aging-related databases such as GeneCards, HAGR, and AgeAnno, we identified 15 aging-related differentially expressed genes (AIDEGs). Correlation and immune infiltration analyses were conducted on these AIDEGs, and diagnostic models were developed using WGCNA, logistic regression, random forest, support vector machine, k-nearest neighbors, and LASSO regression to identify key genes.ResultsAmong these, FCGR1A, CBS, and FASLG emerged as significant biomarkers with strong predictive capabilities for IVDD. Further exploration of biological pathways involving AIDEGs provided insights into their potential roles in IVDD pathogenesis. To further validate these findings, we collected human blood specimens and conducted in vitro experiments. ELISA assays confirmed that CBS and FASLG are crucial biomarkers of IVDD, with distinct expression patterns in patients with moderate versus severe degeneration.DiscussionThese results highlight the diagnostic potential of AIDEGs and provide a new perspective for early intervention and treatment strategies in IVDD.
BackgroundSpinal epidural lipomatosis (SEL) is rare and often ignored or misdiagnosed. Traditional open surgery is considered the standard procedure for treating symptomatic SEL. However, open surgery is often associated with substantial trauma and a long recovery period.Case presentationA 37-year-old female patient was diagnosed with SEL and underwent unilateral biportal endoscopy (UBE) after failure of conservative treatment. The surgery was performed successfully with an estimated blood loss of 20 ml and a whole operation time of 60 min. The patient experienced significant relief of her neurologic symptoms and was discharged 2 days postoperatively. She reported no symptoms other than mild weakness of the low back at the last follow-up 12 months postoperatively. UBE may be an effective alternative to open surgical treatment for symptomatic SEL with the advantages of minimal invasion and quick recovery.ConclusionsSEL is not restricted to the commonly involved lumbosacral region and may occur in other segments of the spine, which should be considered during diagnosis. The advantages of UBE for treating SEL, including minimal invasiveness, muscle preservation, rapid recovery, clear visualization, and effective decompression, make it a viable surgical option; however, its long-term efficacy and safety require further validation.
Study Design Retrospective cohort study. Objectives This study aimed to compare the clinical efficacies of endoscopic surgery and nonsurgical treatment in patients with extruded or sequestered lumbar disc herniation (LDH). Population 613 patients with extruded or sequestrated LDH were included (endoscopic: n = 276; nonsurgical: n = 337). Methods Patients received either endoscopic discectomy or structured nonsurgical management. Longitudinal VAS and ODI trajectories were analyzed using linear mixed-effects models. Return to work (RTW) outcomes were evaluated using Kaplan–Meier survival curves and Cox proportional hazards models. Spearman correlation was used to assess the association between resorption and symptom improvement. Results Both cohorts had comparable sex, BMI, and herniation levels ( P > .05), but differed in age ( P < .001), which did not influence outcomes after adjustment. VAS and ODI improved in both groups over time ( P < .001). Endoscopic discectomy provided faster symptom relief within 6 months ( P < .001), whereas mid to long-term outcomes were comparable between groups ( P > .05). Disc resorption occurred in 58.2% of nonsurgical patients (median time 6.9 months). Resorption was correlated with greater improvements in ODI and VAS ( P < .05). Surgical complications included transient neurological deficits (17.4%), dural tears (1.1%), and epidural hematomas (0.7%). Postoperative recurrence occurred in 8.3% of patients. RTW time was unaffected by treatment, sex, BMI, or herniation level ( P > .05), but was influenced by age (HR = 0.948, P < .001) and occupational demands (HR = 0.697, P < .001). Conclusions Endoscopic discectomy provides faster early pain and functional improvement (≤6 months), while nonsurgical management achieves comparable outcomes thereafter. Disc resorption contributes to symptom recovery. RTW time is determined primarily by age and occupational demands.
Lumbar disc herniation (LDH) is a prevalent condition driven by inflammation, which mediates both radicular pain and spontaneous resorption of herniated material. Traditional anti-inflammatory therapies alleviate pain but may impede disc regression. We propose an Inflammation Preservation Strategy (IPS) to harness inflammation's reparative potential while managing symptoms. Molecular, clinical, and translational evidence reveals inflammation drives resorption in 60-90% of LDH cases. Key mechanisms include neovascularization, dynamic macrophage polarization (where M1 degrades matrix while M2 promotes repair), and apoptosis-autophagy synergy. Traditional anti-inflammatory therapies risk suppressing this reparative cascade, whereas IPS advocates precision modulation-avoiding pan-anti-inflammatory agents during acute phases and employing targeted interventions to balance analgesia with tissue healing. Clinical data support IPS in achieving near-complete resorption and sustained pain relief, suggesting a paradigm shift from symptomatic palliation to disease-modifying regeneration. Future directions include real-time inflammation phenotyping and smart biomaterials to advance precision IPS implementation.
Spinal cord injury (SCI) has a catastrophic impact and lifelong functional incapacity on patients. Recent research has demonstrated the anti-inflammation and neuroprotection of minocycline, which were advantageous for treating disorders having an inflammatory foundation, including SCI. This study summarized the antioxidant, anti-inflammation, and neuro-restoration of minocycline. PubMed, Web of Science, Embase, and Chinese database were explored from their origin date to July 2022. Data extraction, methodological quality assessment, and study selection were conducted by 2 reviewers. Twenty-four studies were ultimately included. Overall, minocycline improved motor recovery after SCI, with Basso Beattie Bresnahan (BBB) scores in the treated group from the first week (15 studies, n = 378; MD = 2.34; 95% Confidence interval (CI), 1.31-3.36; p < 0.00001) to the fourth week (14 studies, n = 346; MD = 3.15; 95% Confidence Interval (CI), 2.07-4.23; p < 0.00001). Subgroup analysis showed function recovery was related to the mode of drug dose, animal race, and article quality. Network pharmacology identified 100 minocycline-related targets and 6720 SCI-related targets. Heat Shock Protein 90 Alpha Family Class A Member 1(HSP90AA1), Serine/Threonine kinase 1(Akt1), Steroid Receptor Coactivator (SRC), Epidermal growth factor receptor (EGFR) and Catenin (Cadherin-Associated Protein)-Beta 1 (CTNNB1) were key targets. 20 pathways were identified, including PI3K/Akt, MAPK and chemokine signaling pathway. Finally, molecular docking results showed B-cell CLL/lymphoma 2 (BCL2-6), CTNNB1, HSP90AA1, plasminogen activator urokinase (PLAU), and α protein kinase C alpha (PRCAKA) bound to minocycline better. This article concluded that minocycline was effective in treating SCI by improving neurological recovery and inhibiting oxidative stress, apoptosis, and inflammation.
Background: To comprehensively assess the neurologic recovery potential of chondroitinase ABC (ChABC) in rats after spinal cord injury (SCI).Methods: The PubMed, Embase, ScienceDirect, Web of Science, and China National Knowledge Infrastructure databases were searched for animal experiments that evaluated the use of ChABC in the treatment of SCI up to November 2022. Studies reporting neurological function using the Basso, Beattie, and Bresnahan (BBB) scale, as well as assessments of cavity area, lesion area, and glial fibrillary acidic protein (GFAP) levels, were included in the analysis.Results: A total of 46 studies were ultimately selected for inclusion. The results of the study showed that rats with SCI that received ChABC therapy exhibited a significant improvement in locomotor function after 7 days compared with controls (32 studies, weighted mean difference (WMD) = 0.58, [0.33, 0.83], p < 0.00001). Furthermore, the benefits of ChABC therapy were maintained for up to 28 days according to BBB scale. The lesion area was reduced by ChABC (5 studies, WMD = -20.94, [-28.42, -13.46], p < 0.00001). Meanwhile, GFAP levels were reduced in the ChABC treatment group (8 studies, WMD = -29.15, [-41.57, -16.72], p < 0.00001). Cavity area is not statistically significant. The subgroup analysis recommended that a single injection of 10 mu L (8 studies, WMD = 2.82, [1.99, 3.65], p < 0.00001) or 20 U/mL (4 studies, WMD = 2.21, [0.73, 3.70], p = 0.003) had a better effect on improving the function. The funnel plot of the BBB scale was found to be essentially symmetrical, indicating a low risk of publication bias.Conclusions: This systematic review and meta-analysis has indicated that ChABC could improve functional recovery in rats after SCI.
Background: Cervical spondylotic myelopathy (CSM) is a degenerative pathology that affects both upper and lower extremity mobility and sensory function, causing significant pressure on patients and society. Prior research has suggested that ginsenosides may have neuroprotective properties in central nervous system diseases. However, the efficacy and mechanism of ginsenosides for CSM have yet to be investigated. Purpose: This study aims to analyze the composition of ginsenosides using UPLC-MS, identify the underlying mechanism of ginsenosides in treating CSM using network pharmacology, and subsequently confirm the efficacy and mechanism of ginsenosides in rats with chronic spinal cord compression. Methods: UPLC-Q-TOF-MS was utilized to obtain mass spectrum data of ginsenoside samples. The chemical constituents of the samples were analyzed by consulting literature reports and relevant databases. Ginsenoside and CSM targets were obtained from the TCMSP, OMIM, and GeneCards databases. GO and KEGG analyses were conducted, and a visualization network of ginsenosides-compounds-key targets-pathways-CSM was constructed, along with molecular docking of key bioactive compounds and targets, to identify the signaling pathways and proteins associated with the therapeutic effects of ginsenosides on CSM. Chronic spinal cord compression rats were intraperitoneally injected with ginsenosides (50 mg/kg and 150 mg/kg) and methylprednisolone for 28 days, and motor function was assessed to investigate the therapeutic efficacy of ginsenosides for CSM. The expression of proteins associated with TNF, IL-17, TLR4/MyD88/NF-kappa B, and NLRP3 signaling pathways was assessed by immunofluorescence staining and western blotting. Results: Using UPLC-Q-TOF-MS, 37 compounds were identified from ginsenoside samples. Furthermore, ginsenosides-compounds-key targets-pathways-CSM visualization network indicated that ginsenosides may modulate the PI3K-Akt signaling pathway, TNF signaling pathway, MAPK signaling pathway, IL-17 signaling pathway, Toll-like receptor signaling pathway and Apoptosis by targeting AKT1, TNF, MAPK1, CASP3, IL6, and IL1B, exerting a therapeutic effect on CSM. By attenuating neuroinflammation through the TNF, IL-17, TLR4/ MyD88/NF-kappa B, and MAPK signaling pathways, ginsenosides restored the motor function of rats with CSM, and ginsenosides 150 mg/kg showed better effect. This was achieved by reducing the phosphorylation of NF-kappa B and the activation of the NLRP3 inflammasome. Conclusions: The results of network pharmacology indicate that ginsenosides can inhibit neuroinflammation resulting from spinal cord compression through multiple pathways and targets. This finding was validated through in vivo tests, which demonstrated that ginsenosides can reduce neuroinflammation by inhibiting NLRP3 inflammasomes via multiple signaling pathways, additionally, it should be noted that 150 mg/kg was a relatively superior dose. This study is the first to verify the intrinsic molecular mechanism of ginsenosides in treating CSM by combining pharmacokinetics, network pharmacology, and animal experiments. The findings can provide evidence for subsequent clinical research and drug development.
Introduction: Magnetic Resonance Imaging (MRI) is essential in diagnosing cervical spondylosis, providing detailed visualization of osseous and soft tissue structures in the cervical spine. However, manual measurements hinder the assessment of cervical spine sagittal balance, leading to time-consuming and error-prone processes. This study presents the Pyramid DBSCAN Simple Linear Iterative Cluster (PDB-SLIC), an automated segmentation algorithm for vertebral bodies in T2-weighted MR images, aiming to streamline sagittal balance assessment for spinal surgeons.Method: PDB-SLIC combines the SLIC superpixel segmentation algorithm with DBSCAN clustering and underwent rigorous testing using an extensive dataset of T2-weighted mid-sagittal MR images from 4,258 patients across ten hospitals in China. The efficacy of PDB-SLIC was compared against other algorithms and networks in terms of superpixel segmentation quality and vertebral body segmentation accuracy. Validation included a comparative analysis of manual and automated measurements of cervical sagittal parameters and scrutiny of PDB-SLIC’s measurement stability across diverse hospital settings and MR scanning machines.Result: PDB-SLIC outperforms other algorithms in vertebral body segmentation quality, with high accuracy, recall, and Jaccard index. Minimal error deviation was observed compared to manual measurements, with correlation coefficients exceeding 95%. PDB-SLIC demonstrated commendable performance in processing cervical spine T2-weighted MR images from various hospital settings, MRI machines, and patient demographics.Discussion: The PDB-SLIC algorithm emerges as an accurate, objective, and efficient tool for evaluating cervical spine sagittal balance, providing valuable assistance to spinal surgeons in preoperative assessment, surgical strategy formulation, and prognostic inference. Additionally, it facilitates comprehensive measurement of sagittal balance parameters across diverse patient cohorts, contributing to the establishment of normative standards for cervical spine MR imaging.
Recent research in computational imaging largely focuses on developing machine learning (ML) techniques for image recognition in the medical field, which requires large-scale and high-quality training datasets consisting of raw images and annotated images. However, suitable experimental datasets for cervical spine X-ray are scarce. We fill the gap by providing an open-access Cervical Spine X-ray Atlas (CSXA), which includes 4963 raw PNG images and 4963 annotated images with JSON format (JavaScript Object Notation). Every image in the CSXA is enriched with gender, age, pixel equivalent, asymptomatic and symptomatic classifications, cervical curvature categorization and 118 quantitative parameters. Subsequently, an efficient algorithm has developed to transform 23 keypoints in images into 77 quantitative parameters for cervical spine disease diagnosis and treatment. The algorithm’s development is intended to assist future researchers in repurposing annotated images for the advancement of machine learning techniques across various image recognition tasks. The CSXA and algorithm are open-access with the intention of aiding the research communities in experiment replication and advancing the field of medical imaging in cervical spine.
Cervical spondylotic myelopathy (CSM) is a severe non-traumatic spinal cord injury (SCI) wherein the spinal canal and cervical cord are compressed due to the degeneration of cervical tissues. To explore the mechanism of CSM, the ideal model of chronic cervical cord compression in rats was constructed by embedding a polyvinyl alcohol-polyacrylamide hydrogel in lamina space. Then, the RNA sequencing technology was used to screen the differentially expressed genes (DEGs) and enriched pathways among intact and compressed spinal cords. A total of 444 DEGs were filtered out based on the value of log2(Compression/Sham); these were associated with IL-17, PI3K-AKT, TGF-β, and Hippo signaling pathways according to the GSEA, KEGG, and GO analyses. Transmission electron microscopy indicated the changes in mitochondrial morphology. Western blot and immunofluorescence staining revealed neuronal apoptosis, astrogliosis and microglial neuroinflammation in the lesion area. Specifically, the expression of apoptotic indicators, such as Bax and cleaved caspase-3, and inflammatory cytokines, such as IL-1β, IL-6, and TNF-α, were upregulated. The activation of IL-17 signaling pathway was observed in microglia instead of neurons or astrocytes, the activation of TGF-β and inhibition of Hippo signaling pathways were detected in astrocytes instead of neurons or microglia, and the inhibition of PI3K-AKT signaling pathway was discovered in neurons rather than microglia of astrocytes in the lesion area. In conclusion, this study indicated that neuronal apoptosis was accompanied by inhibiting of the PI3K-AKT pathway. Then, the activation of microglia IL-17 pathway and NLRP3 inflammasome effectuated the neuroinflammation, and astrogliosis was ascribed to the activation of TGF-β and the inhibition of the Hippo pathway in the chronic cervical cord of compression. Therefore, therapeutic methods targeting these pathways in nerve cells could be promising CSM treatments.
The animal experiment is the best method for therapeutic efficacy testing of various treatment methods before clinical application and serves as an irreplaceable “live reagent” and “live precise instrument,” thus playing a vital role in biomedical science research. However, there were significant differences between the results of animal experiments and clinical efficacy in previous findings that are hard to ignore, especially in cerebrovascular accident research due to the unsatisfactory specification of animal experiments. Accordingly, more prescriptive and standard tools are required for evaluating the quality of animal experiments. This study will introduce the current commonly used quality evaluation tools for animal experiments.
Cervical spondylotic myelopathy (CSM) refers to a chronic injury of the cervical cord caused by cervical intervertebral disc degeneration. Endoplasmic reticulum (ER) homeostasis is essential to counteract neuronal apoptosis. ER stress, an integral part of ER homeostasis, was observed in a rat model of chronic cervical cord compression in our previous study. However, the correlation between ER homeostasis and CSM remains unknown. The antioxidant melatonin is known to exert therapeutic effects in acute spinal cord injury, but the specific effects and their potential mechanisms in the pathological processes of CSM require further exploration. The present study hypothesized that ER homeostasis is essential for neuronal apoptosis in the CSM and that melatonin maintains this homeostasis. The results showed that ER stress led to neuronal apoptosis in rats with chronic cervical cord compression. Conversely, melatonin attenuates protein kinase R‐like ER kinase‐eukaryotic initiation factor 2α‐C/EBP‐homologous protein, inositol‐requiring enzyme 1, and transcription factor 6 signaling pathways to release ER stress and prevents Bax translocation to the mitochondrion, thereby promoting motor recovery and protecting neurons in vivo. It also rescued primary rat cortical neurons from ER stress‐induced glutamate toxicity in vitro. Moreover, melatonin remodels the ER morphology and restores homeostasis via ER‐phagy in injured neurons. FAM134B, CCPG1, RTN3, and Sec. 62 are four known ER‐phagy receptors. In this study, Sec. 62 was identified as a key melatonin factor in promoting ER‐phagy and restoring ER homeostasis in damaged neurons in vivo and in vitro. In conclusion, melatonin suppresses neuronal apoptosis by reducing ER stress and promoting ER‐phagy to restore ER morphology and homeostasis. The current results suggested that melatonin is a promising treatment for CSM owing to its restorative effect on ER homeostasis; however, well‐designed randomized controlled trials must be carried out to further investigate its clinical effects.
Purpose:The purpose of this study was to construct an animal model of Graves' ophthalmopathy (GO) by comparing recombinant adenovirus expressing human thyrotropin receptor A subunit (Ad-TSHR A) gene immunization and dendritic cell (DC) immunization. We evaluated the animal models that are closer to the pathology of human GO, and laid the foundation for the study of GO.Materials and Methods:Ad-TSHR A was injected intramuscularly into female BALB/c mice to induce the GO animal model. A GO animal model was constructed using TSHR combined with IFN-γ-modified primary DC immunized female BALB/c. The animal models constructed by the above two methods were evaluated in terms of ocular appearance, serology, pathology, and imaging to assess the modeling rate of the animal models, respectively.Results:Both modeled mice exhibited increased serological indexes of free thyroxine (FT4) and TSH receptor antibodies (TRAbs) levels and decreased TSH (P < 0.01). Thyroid pathology analysis revealed the number of thyroid follicles increases, the size varies, and the follicular epithelial cells proliferate to varying degrees in a cuboidal or tall columnar pattern, with a small amount of lymphocytic infiltration visible. Adipose tissue behind the eyeball was accumulated, the muscle outside the eyeball was broken and fibrotic, and hyaluronic acid (HA) behind the eyeball was increased. The animal model of GO constructed by immunization of TSHR with IFN-γ-modified DC had a modeling rate of 60%, whereas that of Ad-TSHR A gene immunization was 72%.Conclusions:Both gene immunization and cellular immunization can be used to construct GO models, and the modeling rate of gene immunization is higher than that of cellular immunization.Translational Relevance:In this study, two innovative methods, cellular immunity and gene immunity, were used to establish GO animal models, which improved the success rate to a certain extent. To our knowledge, this study presents the first cellular immunity modeling idea of TSHR combined with IFN-γ for the GO animal model, which provides an animal model basis for understanding the pathogenesis of GO and developing new treatment methods.
目的巨大/破裂型腰椎间盘突出症由于突出物巨大,临床往往行手术治疗.姜宏教授总结多年临床经验,根据突出物MRI表现进行临床转归预测,提出中医保守治疗腰椎间盘突出症的专方"消髓化核汤",认为黄芪、威灵仙、木瓜等为促进突出物重吸收的专药,尤其适用于巨大/破裂型突出.在辨病采用专方、专药论治的基础上结合辨型、辨证、辨期论治,可有效改善临床症状,促进突出物重吸收,临床疗效显著.
Background: In neck pain treatment, many therapies are focused on etiology, while it is well-known that placebo analgesia is also present in these therapies. The specific efficacy for etiology may be underestimated by ignoring their actual placebo effect. In this study, a logistic regression analysis is used to explore the risk factors causing different placebo responses in patients with neck pain among two RCTs. The probability of the placebo effect is predicted based on these risk factors.Methods: Trial A and Trial B were similarly designed, randomized, double-/single-blind, placebo-controlled trials in patients treating neck pain with Qishe pill or Shi-style manipulation. Both studies set a placebo pill twice a day or traction for every other day as control. For further analyses on the placebo effect in neck pain management, logistic regression was used to assess subgroup-placebo interactions. The odds ratio assessed a significant influence on the placebo effect.Results: In this pooled analysis, the total number of patients recruited for these two studies was 284, of which 162 patients received placebo treatment (placebo drug or traction for every other day). No statistically significant differences are found at baseline between the participants with placebo effect and non-placebo effect in the gender, age, and disease duration except in VAS and NDI at the initial time. There are numerically more patients with placebo effect in the shorter disease duration subgroup (< 4 months [76%]), higher initial VAS subgroup (>60 mm [90%]), and worse initial NDI subgroup (>24 [72%]) compared with the gender and age subgroup. An ROC curve is established to assess the model-data fit, which shows an area under the curve of 0.755 and a 95% confidence interval of 0.677-0.830. Participants who show placebo effect after 2 weeks have significantly lower VAS scores after 4 weeks, while there is no significant difference in NDI improvement between the two groups after 4 weeks.Conclusion: Neck pain patients with shorter disease duration are more likely to overscore their pain severity, because of their less experience in pain perception, tolerance, and analgesia expectation.