Background Both inflammatory factors and immune response play important roles in the pathogenesis of intervertebral disc degeneration (IDD). However, a comprehensive analysis of interaction between inflammatory response-associated genes (IRGs) and immune microenvironment in patients with IDD remains lacking. Hence, the current research is aimed at investigating the correlations between IRG signatures and immune cells in the progression of IDD. Methods The expression profiles (GSE27494 and GSE41883) and IRGs were downloaded from the Gene Expression Omnibus (GEO) database and Molecular Signature Database (MSigDB), respectively. Weighted gene coexpression network analysis (WGCNA) and differential expression analysis were used to identify the pivotal modules and common differentially expressed genes (DEGs) associated with IDD. Subsequently, we retrieved differentially expressed IRGs (DE-IRGs) by intersecting IRGs and DEGs for enrichment analysis. Next, LASSO regression analyses were performed to screen optimal marker genes for IDD prediction. Additionally, we validated differences DE-IRGs between IDD patients and controls in GSE150408. Finally, the infiltration alteration of immune cells was evaluated by the CIBERSORT, and the correlation between diagnostic markers and infiltrating immune cells was analyzed. Results A total of 10 upregulated differentially expressed inflammatory genes were identified that were obviously related to progression of IDD. Functional analysis results revealed that DE-IRGs were mainly enriched in signaling pathways TNF, IL-17, NOD-like receptor, and NF-kappa B pathway. A five-gene signature that consisted of IL-1β, LIF, LYN, NAMPT, and SLC7A2 was constructed by the LASSO Cox regression. IL1B, LYN, and NAMPT were further validated as optimal candidate genes in the pathophysiology of IDD. In addition, there was a remarkable immune cell infiltration difference between the healthy and IDD groups. The proportions for dendritic cells activated, mast cells activated, and neutrophils in the IDD group were significantly higher than those in the normal group, while the proportion of some cells was lower than that of the normal group, such as T cell CD4 memory resting, NK cells activated, and macrophage M0. Furthermore, correlation analysis indicated IL-1β, LYN, and NAMPT were closely implicated with immune cell infiltration in IDD development. Conclusions We explored an association between inflammatory response-associated signature and immune infiltration in IDD and validated that IL-1β, LYN, and NAMPT might serve as biomarkers and therapeutic targets for IDD in the future.

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Development of a Novel Inflammatory-Associated Gene Signature and Immune Infiltration Patterns in Intervertebral Disc Degeneration

*Department of Physical Medicine and Rehabilitation, University of Utah, Salt Lake City, UT, USA; Department of Orthopaedics, Stanford University, Redwood City, CA, USA; The University of Texas Dell Medical School, Ascension Texas Spine and Scoliosis, Austin, TX, USA; Department of Orthopaedics, University of California San Francisco, San Francisco, CA, USA; Virginia iSpine Physicians, PC, Richmond, VA, USA

Vertebrogenic Pain: A Paradigm Shift in Diagnosis and Treatment of Axial Low Back Pain

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Comparison of cooled versus conventional radiofrequency treatment of the genicular nerves for chronic knee pain: a multicenter non-inferiority randomized pilot trial (COCOGEN trial)

Abstract Objective Multiple studies have demonstrated the safety and effectiveness of basivertebral nerve radiofrequency ablation (BVN RFA) for improving low back pain related to the vertebral endplate. However, the influence of patient demographic and clinical characteristics on treatment outcome is unknown. Design Pooled cohort study of three clinical trials of patients with vertebral endplate pain identified by Type 1 and/or Type 2 Modic changes and a correlating presentation of anterior spinal element pain. Setting Thirty-three global study centers. Subjects Patients (n = 296) successfully treated with BVN RFA. Methods Participant demographic and clinical characteristics were analyzed with stepwise logistic regression to identify predictors of treatment success. Three definitions of treatment success were defined: 1) ≥50% visual analog scale pain improvement, 2) ≥15-point Oswestry Disability Index (ODI) improvement, and 3) ≥50% visual analog scale or ≥15-point ODI improvement from baseline. Results Low back pain of ≥5 years’ duration and higher ODI scores at baseline increased the odds of treatment success, whereas baseline opioid use and higher Beck Depression Inventory scores reduced these odds. However, the three regression models demonstrated receiver-operating characteristics of 62–70% areas under the curve, and thus, limited predictive capacity. Conclusions This analysis identified no demographic or clinical characteristic that meaningfully increased or reduced the odds of treatment success from BVN RFA. On the basis of these findings and the high response rates from the three analyzed trials, we recommend the use of objective imaging biomarkers (Type 1 and/or 2 Modic changes) and a correlating presentation of anterior spinal element pain to determine optimal candidacy for BVN RFA.

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The Relationship Between Patient Demographic and Clinical Characteristics and Successful Treatment Outcomes After Basivertebral Nerve Radiofrequency Ablation: A Pooled Cohort Study of Three Prospective Clinical Trials

Abstract Objective Investigate associations between endplate and motion segment magnetic resonance imaging (MRI) characteristics and treatment outcomes following basivertebral nerve radiofrequency ablation (BVN RFA) in patients with clinically suspected vertebral endplate pain (VEP). Design Aggregated cohort study of 296 participants treated with BVN RFA from three prospective clinical trials. Methods Baseline MRI characteristics were analyzed using stepwise logistic regression to identify factors associated with treatment success. Predictive models used three definitions of treatment success: (1) ≥50% low back pain (LBP) visual analog scale (VAS), (2) ≥15-point Oswestry Disability Index (ODI), and (3) ≥50% VAS or ≥15-point ODI improvements at 3-months post-BVN RFA. Results The presence of lumbar facet joint fluid (odds ratio [OR] 0.586) reduced the odds of BVN RFA treatment success in individuals with clinically suspected VEP. In patients with a less advanced degenerative disc disease (DDD) profile, a > 50% area of the endplate with bone marrow intensity changes (BMIC) was predictive of treatment success (OR 4.689). Both regressions areas under the curve (AUCs) were under 70%, indicating low predictive value. All other vertebral endplate, intervertebral disc, nerve roots facet joint, spinal segmental alignment, neuroforamina, lateral recesses, and central canal MRI characteristics were not associated with BVN RFA success. Conclusions In patients with vertebrogenic low back pain with Modic changes, the presence of degenerative findings of the anterior and posterior column was not associated with a clinically important impact on BVN RFA treatment success. None of the models demonstrated strong predictive value, indicating that the use of objective imaging biomarkers (Type 1 and/or 2 Modic changes) and a correlating presentation of pain remain the most useful patient selection factors for BVN RFA.

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Magnetic Resonance Imaging Characteristics Associated with Treatment Success from Basivertebral Nerve Ablation: An Aggregated Cohort Study of Multicenter Prospective Clinical Trials Data

Abstract Objective To provide an estimate of the effectiveness of basivertebral nerve (BVN) radiofrequency ablation (RFA) to treat vertebrogenic low back pain (LBP). Design Systematic review with single-arm meta-analysis. Population Persons ≥18 years of age with chronic LBP associated with type 1 or 2 Modic changes. Intervention Intraosseous BVN RFA. Comparison Sham, placebo procedure, active standard care treatment, or none. Outcomes The proportion of patients treated with BVN RFA who reported ≥50% pain score improvement on a visual analog scale or numeric rating scale. The main secondary outcome was ≥15-point improvement in Oswestry Disability Index score. Methods Three reviewers independently assessed articles published before December 6, 2021, in MEDLINE and Embase. The Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) framework was used to evaluate the overall quality of evidence. Results Of the 856 unique records screened, 12 publications met the inclusion criteria, representing six unique study populations, with 414 participants allocated to receive BVN RFA. Single-arm meta-analysis showed a success rate of 65% (95% confidence interval [CI] 51–78%) and 64% (95% CI 43–82%) for ≥50% pain relief at 6 and 12 months, respectively. Rates of ≥15-point Oswestry Disability Index score improvement were 75% (95% CI 63–86%) and 75% (95% CI 63–85%) at 6 and 12 months, respectively. Conclusion According to GRADE, there is moderate-quality evidence that BVN RFA effectively reduces pain and disability in most patients with vertebrogenic LBP. Further high-quality studies will likely improve our understanding of the effectiveness of this procedure.

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The Effectiveness of Intraosseous Basivertebral Nerve Radiofrequency Ablation for the Treatment of Vertebrogenic Low Back Pain: An Updated Systematic Review with Single-Arm Meta-analysis

Radiofrequency Ablation for Zygapophyseal Joint Pain.

Genicular nerve radiofrequency ablation (GNRFA) is an effective treatment for chronic knee pain related to osteoarthritis. It is often utilized when conservative management has failed and patients wish to avoid arthroplasty, are poor surgical candidates due to co-morbid medical conditions, or in those suffering from persistent pain after arthroplasty. The classic targets for GNRFA include the superior lateral genicular nerve, superior medial genicular nerve, and inferior medial genicular nerve but multiple anatomic studies have demonstrated additional sensory innervation to the knee. In this research article, we propose an image-guided technique that can safely target the infrapatellar branch of the saphenous nerve which also provides sensory innervation to the anterior capsule. The proposed technique includes variations for conventional bipolar radiofrequency ablation, cooled radiofrequency ablation, dual-tined bipolar radiofrequency ablation, and monopolar radiofrequency ablation using a long axis approach. The described technique is based on updated anatomic studies and takes into account safety concerns such as thermal risk to the skin and/or pes anserine tendons and breaching of the synovial cavity. Future clinical research should be performed to confirm the safety and effectiveness of this specific approach.

Aaron Conger

Papers

The Effectiveness of Intraosseous Basivertebral Nerve Radiofrequency Ablation for the Treatment of Vertebrogenic Low Back Pain: An Updated Systematic Review with Single-Arm Meta-analysis

Vertebrogenic Pain: A Paradigm Shift in Diagnosis and Treatment of Axial Low Back Pain

Radiofrequency Ablation for Zygapophyseal Joint Pain.

Magnetic Resonance Imaging Characteristics Associated with Treatment Success from Basivertebral Nerve Ablation: An Aggregated Cohort Study of Multicenter Prospective Clinical Trials Data

Radiofrequency Ablation of the Infrapatellar Branch of the Saphenous Nerve for the Treatment of Chronic Anterior Inferomedial Knee Pain.