Lumbar intervertebral disc degeneration in low back pain.

Intervertebral disc degeneration is characterized by deterioration in structural support that is potentially followed by stimulated neuronal ingrowth, and dysfunction of cellular physiology in the disc. Discogenic low back pain originates from nociceptors within the intervertebral disc or the cartilage endplate. This narrative review examines the mechanisms of disc degeneration, the association between degeneration and pain, and the current diagnosis and treatment of discogenic low back pain. Mechanisms of disc degeneration include dysregulated homeostasis of the extracellular matrix of the disc, altered spine mechanics, DNA damage, oxidative stress, perturbed cell signaling pathways, and cellular senescence. Although disc degeneration is more common in individuals with low back pain than in asymptomatic ones, degeneration occurs in a large proportion of asymptomatic individuals. Therefore, degeneration itself is not sufficient to trigger low back pain. Imaging and discography are common diagnostic tools of discogenic low back pain but have limited validity to diagnose discogenic pain. Most of current treatments options are not specific to discogenic pain but are unspecific treatments of low back pain of any origin. There is an urgent need to clarify and distinguish the molecular mechanisms of discogenic pain from mechanisms of disc degeneration that are not involved in nociception. Future research should make use of current methods to study molecular mechanisms of human pain in comprehensively and quantitatively phenotyped patients with low back pain, with the objective to identify molecular triggers of discogenic pain and determine the relationship between molecular mechanisms, pain, and patient-relevant outcomes.

Obstetric-related lower back pain: the effect of number of pregnancy on development of chronic lower back pain, worsening of lumbar disc degeneration and alteration of lumbar sagittal balance.

OBJECTIVE: This study aims to determine whether the number of pregnancies contributes to the development of chronic lower back pain, worsening the lumbar disc degeneration and altering the normal lumbar sagittal balance. MATERIAL METHOD: There are 134 ladies participated in this study. They are divided into two groups based on their number of pregnancies (parity). All patients with chronic back pain were assessed using a visual analog scale for pain and the Oswestry Disability Index for their functional status assessment. Degenerative signs in lumbar MRI, which are Modic changes and the presence of Schmorl's node, were evaluated. Besides that, the sagittal balance of the lumbar spine was also measured via an erect lumbar plain radiograph. RESULTS: Patients with parities < 5 were included in Group 1, and those with parities ≥ 5 in Group 2. The mean visual analog scale score of Group 2 was significantly higher than that of Group 1 (8.42 ± 1.34 vs.6.50 ± 1.61). The mean Oswestry Disability Index score in Group 2 was significantly higher than that of Group 1 (29.87 ± 6.75 vs.18.41 ± 7.97). This relationship between the groups in terms of Modic change was statistically significant. The relationship between the groups regarding the presence of Schmorl's nodes was also statistically significant. The difference between the groups in terms of sagittal balance parameters was not statistically significant. CONCLUSION: Chronic lower back pain is significantly worse and associated with more disability in patients with more than five previous pregnancies. MRI degenerative changes are also significantly higher in these grand multipara groups.

Modic Changes in the Lumbar Spine: Exploring Their Association with Abdominal Aortic Calcification as a Potential Indicator of Systemic Atherosclerosis.

BACKGROUND: This was a cross-sectional study on the correlation between abdominal aortic calcification (AAC) and Modic changes (MC). Little is known regarding the etiology of MC in the lumbar spine. Currently, insufficient vascularization of the endplate has been proposed to contribute to the appearance of MC. Our objective was to investigate whether AAC, a marker for a poor vascular status, is associated with MC in patients suffering from degenerative disc disease. METHODS: Radiologic images of patients (n = 130) suffering from degenerative lumbar disc disease were reviewed. Type and severity of MC were assessed using magnetic resonance images, and severity of AAC was evaluated using computed tomography images or fluoroscopy. Both items were dichotomized into minimal and relevant grades. The correlation between them was studied using Spearman's correlation test, with age as a covariate. RESULTS: Of the patients, 113 (87%) demonstrated MC (31% type I, 63% type II, and 6% type III) (55% relevant grade), and 68% had AAC (44% relevant grade). Spearman statistical analysis revealed that AAC was correlated with age (P < 0.001), whereas MC were not (P = 0.142). AAC severity was significantly correlated with MC, remaining so after age adjustment (P < 0.05). While MC type I lacked correlation with AAC, MC type II were significantly correlated with AAC (0.288, P = 0.015); however, this association lost significance after adjusting for age (P = 0.057). CONCLUSIONS: AAC and MC (mainly MC type II) are associated, indicating that reduced blood supply or even a poor systemic vascularization status due to atherosclerotic disease may play a role in the formation of MC. Future studies focusing on the etiology of MC should pay more attention to patients' vascular status and determinants of abdominal aorta calcification.

Reconsidering high intensity zones: its role in intervertebral disk degeneration and low back pain.

PURPOSE: High intensity zones (HIZ) in the lumbar intervertebral disk (IVD) can be associated with degenerative changes which may ultimately manifest as low back pain (LBP). However, the relationship between the prevalence of HIZ and lumbar degenerative parameters is still unclear. The purpose of this study was to determine the prevalence of HIZ in the lumbar spine, analyze the independent relationship between HIZ and lumbar degenerative parameters measured on MRI and X-ray and determine the association between HIZ and the presence of LBP. METHODS: A retrospective review of MRI data, X-ray data, and radiology reports for 136 consecutively recruited patients, above 18-years-age and with both lumbar MRI and X-ray scans was conducted. 57 patients with HIZ were identified. Patients without HIZ (n = 79) made up the control group. RESULTS: HIZ was prevalent in 41.9% of patients and in 11.0% of all lumbar IVDs. The odds of developing HIZ were 6.4 (Exp(B) 6.4, 95%CI [3.157-12.988]) and 3.0 (Exp(B) 3.0, 95%CI [1.603, 5.674]) times higher in IVDs with disk bulge/protrusion and nucleus degeneration, respectively. Odds of HIZ was also increased in disks with larger IVD angle (Exp(B) 1.1, 95%CI [1.034, 1.169]). The odds of patients presenting to imaging with LBP was 3.0 (OR 3.0, 95%CI [1.478-6.338]) times higher in the HIZ compared to the control group. CONCLUSIONS: HIZ was prevalent in 41.9% of participants that were recruited in this study. Nucleus degeneration, disk bulge/protrusion and increased IVD angle were found to be independently associated with HIZ and since there is an increased likelihood of LBP, we posit that HIZ is likely a symptomatic and clinically meaningful diagnostic tool in the assessment of LBP.

Obesity increases the odds of intervertebral disc herniation and spinal stenosis; an MRI study of 1634 low back pain patients.

PURPOSE: The objective of this study was to examine the relationships between BMI and intervertebral disc degeneration (DD), disc herniation (DH) and spinal stenosis (SS) using a large, prospectively recruited and heterogeneous patient population. METHODS: Patients were recruited through the European Genodisc Study. An experienced radiologist scored MRI images for DD, DH and SS. Multivariate linear and logistic regression analyses were used to model the relationship between these variables and BMI with adjustment for patient and MRI confounders. RESULTS: We analysed 1684 patients with a mean age of 51 years and BMI of 27.2 kg/m2.The mean DD score was 2.6 (out of 5) with greater DD severity with increasing age (R2 = 0.44). In the fully adjusted model, a 10-year increase in age and a 5 kg/m2 increase in BMI were associated, respectively, with a 0.31-unit [95% CI 0.29,0.34] and 0.04-unit [CI 0.01,0.07] increase in degeneration. Age (OR 1.23 [CI 1.06,1.43]) and BMI (OR 2.60 [CI 2.28,2.96]) were positively associated with SS. For DH, age was a negative predictor (OR 0.70 [CI 0.64,0.76]) but for BMI (OR 1.19 [CI 1.07,1.33]), the association was positive. BMI was the strongest predictor of all three features in the upper lumbar spine. CONCLUSIONS: While an increase in BMI was associated with only a slight increase in DD, it was a stronger predictor for DH and SS, particularly in the upper lumbar discs, suggesting weight loss could be a useful strategy for helping prevent disorders associated with these pathologies.

Annulus Fibrosus Injury Induces Acute Neuroinflammation and Chronic Glial Response in Dorsal Root Ganglion and Spinal Cord-An In Vivo Rat Discogenic Pain Model.

Chronic painful intervertebral disc (IVD) degeneration (i.e., discogenic pain) is a major source of global disability needing improved knowledge on multiple-tissue interactions and how they progress in order improve treatment strategies. This study used an in vivo rat annulus fibrosus (AF) injury-driven discogenic pain model to investigate the acute and chronic changes in IVD degeneration and spinal inflammation, as well as sensitization, inflammation, and remodeling in dorsal root ganglion (DRG) and spinal cord (SC) dorsal horn. AF injury induced moderate IVD degeneration with acute and broad spinal inflammation that progressed to DRG to SC changes within days and weeks, respectively. Specifically, AF injury elevated macrophages in the spine (CD68) and DRGs (Iba1) that peaked at 3 days post-injury, and increased microglia (Iba1) in SC that peaked at 2 weeks post-injury. AF injury also triggered glial responses with elevated GFAP in DRGs and SC at least 8 weeks post-injury. Spinal CD68 and SC neuropeptide Substance P both remained elevated at 8 weeks, suggesting that slow and incomplete IVD healing provides a chronic source of inflammation with continued SC sensitization. We conclude that AF injury-driven IVD degeneration induces acute spinal, DRG, and SC inflammatory crosstalk with sustained glial responses in both DRGs and SC, leading to chronic SC sensitization and neural plasticity. The known association of these markers with neuropathic pain suggests that therapeutic strategies for discogenic pain need to target both spinal and nervous systems, with early strategies managing acute inflammatory processes, and late strategies targeting chronic IVD inflammation, SC sensitization, and remodeling.

A rare case of intervertebral disc calcification combined with ossification of the posterior longitudinal ligament in a child: a case report and literature review.

BACKGROUND: Intervertebral disc calcification (IDC) combined with calcification in children has been sporadically reported, while ossification of the posterior longitudinal ligament (OPLL) in the cervical spine in pediatric patients is exceedingly rare. The aim of this study is to investigate the potential prognosis and outcomes associated with this condition. CASE PRESENTATION: We present an unusual case involving a 10-year-old Chinese child diagnosed with calcified cervical disc herniation and ossification of the posterior longitudinal ligament. Conservative treatment measures were implemented, and at the 1-month and 6-month follow-up, the patient's pain exhibited significant improvement. Subsequent cervical MRI and CT scans revealed the complete disappearance of OPLL and substantial absorption of the calcified disc. During the three-month follow-up, CT demonstrated slight residual disc calcification, however, the patient remained asymptomatic with no discernible limitation in cervical motion. CONCLUSIONS: We conducted a comprehensive review of several cases presenting with the same diagnosis. It is noteworthy that IDC combined with OPLL in children constitutes a rare clinical entity. Despite imaging indications of potential spinal canal occupation, the majority of such cases demonstrate complete absorption following conservative treatment, with OPLL exhibiting a faster absorption rate than calcified discs.

Does intervertebral disc degeneration in adolescent idiopathic scoliosis correlate with patient-reported pain scores? A review of 968 cases.

PURPOSE: Report the rate and severity of degenerative disc disease (DDD) in non-surgical adolescent idiopathic scoliosis (AIS) patients and correlate these findings with patient-reported symptomatology scores. Additionally, to quantify the rate of concurrent pathological radiological findings in this group. METHODS: This was a retrospective chart review study at a single tertiary centre. AIS patients aged 10-16 who had received a whole spine MRI between September 2007 and January 2019 and who had not received surgical intervention to their spine were included. MRI scan reports were screened to extract those who had evidence of DDD. These were then reviewed by a blinded second reviewer who graded every disc using the Pfirrmann grading system. SRS-22 scores were extracted for patients when available. RESULTS: In total, 968 participants were included in the study. Of these, 93 (9.6%) had evidence of DDD, which was Pfirrmann grade ≥ 3 in 28 (2.9%). The most commonly affected level was L5/S1 (59.1% of DDD cases). A total of 55 patients (5.7%) had evidence of syringomyelia, 41 (3.4%) had evidence of spondylolisthesis (all L5/S1), 14 (1.4%) had bilateral L5 pars defects, and 5 (0.5%) had facet joint degeneration. Spondylolisthesis and bilateral pars defects were more common in patients with DDD identified on MRI scan (p < 0.001 and p = 0.04, respectively). Function (p = 0.048) and pain (p = 0.046) scores were worse in patients with DDD. CONCLUSION: We present a baseline for the rate and severity of DDD in the non-operative AIS cohort. This should assist in decision-making and counselling of patients prior to surgery. LEVEL OF EVIDENCE: III.

Imaging of Discogenic and Vertebrogenic Pain.

Chronic low back pain is a major source of pain and disability globally involving multifactorial causes. Historically, intervertebral disc degeneration and disruption have been associated as primary back pain triggers of the anterior column, termed "discogenic pain." Recently, the vertebral endplates have been identified as another possible pain trigger of the anterior column. This "endplate-driven" model, defined "vertebrogenic pain," is often interconnected with disc degeneration. Diagnosis of vertebrogenic and discogenic pain relies on imaging techniques that isolate pain generators and exclude comorbid conditions. Traditional methods, like radiographs and discography, are augmented by more sensitive methods, including SPECT, CT, and MRI. Morphologic MRI is pivotal in revealing indicators of vertebrogenic (eg, Modic endplate changes) and discogenic pain (eg, disc degeneration and annular fissures). More advanced methods, like ultra-short-echo time imaging, and quantitative MRI further amplify MRI's accuracy in the detection of painful endplate and disc pathology. This review explores the pathophysiology of vertebrogenic and discogenic pain as well as the impact of different imaging modalities in the diagnosis of low back pain. We hope this information can help identify patients who may benefit from personalized clinical treatment and image-guided therapies.

An Engineered Bionic Nanoparticle Sponge as a Cytokine Trap and Reactive Oxygen Species Scavenger to Relieve Disc Degeneration and Discogenic Pain.

The progressive worsening of disc degeneration and related nonspecific back pain are prominent clinical issues that cause a tremendous economic burden. Activation of reactive oxygen species (ROS) related inflammation is a primary pathophysiologic change in degenerative disc lesions. This pathological state is associated with M1 macrophages, apoptosis of nucleus pulposus cells (NPC), and the ingrowth of pain-related sensory nerves. To address the pathological issues of disc degeneration and discogenic pain, we developed MnO2@TMNP, a nanomaterial that encapsulated MnO2 nanoparticles with a TrkA-overexpressed macrophage cell membrane (TMNP). Consequently, this engineered nanomaterial showed high efficiency in binding various inflammatory factors and nerve growth factors, which inhibited inflammation-induced NPC apoptosis, matrix degradation, and nerve ingrowth. Furthermore, the macrophage cell membrane provided specific targeting to macrophages for the delivery of MnO2 nanoparticles. MnO2 nanoparticles in macrophages effectively scavenged intracellular ROS and prevented M1 polarization. Supportively, we found that MnO2@TMNP prevented disc inflammation and promoted matrix regeneration, leading to downregulated disc degenerative grades in the rat injured disc model. Both mechanical and thermal hyperalgesia were alleviated by MnO2@TMNP, which was attributed to the reduced calcitonin gene-related peptide (CGRP) and substance P expression in the dorsal root ganglion and the downregulated Glial Fibrillary Acidic Protein (GFAP) and Fos Proto-Oncogene (c-FOS) signaling in the spinal cord. We confirmed that the MnO2@TMNP nanomaterial alleviated the inflammatory immune microenvironment of intervertebral discs and the progression of disc degeneration, resulting in relieved discogenic pain.

The disc-endplate-bone-marrow complex classification: progress in our understanding of Modic vertebral endplate changes and their clinical relevance.

BACKGROUND CONTEXT: The disc, endplate (EP), and bone marrow region of the spine form a single anatomical and functional interdependent unit; isolated degeneration of any one structure is rare. Modic changes (MC), however, are restricted to the subchondral bone alone and based on only T1 and T2 sequences of MRI. This results in poor reliability in differentiating fat from edema and hence may give a false impression of disease inactivity. PURPOSE: To study the changes in disc, endplate, and bone marrow as a whole in degeneration and propose a classification based on the activity status of this complex with the addition of STIR MRI sequences. STUDY DESIGN: Observational cohort. PATIENT SAMPLE: Patients with isolated brain, cervical, or thoracic spine injury and patients with low back pain (LBP) who underwent MRI formed the control and study groups, respectively. OUTCOME MEASURES: Demographic data, the prevalence of MC and disc-endplate-bone marrow classification (DEBC) changes, EPs undergoing reclassification based on DEBC, and comparison of the prevalence of MC, DEBC, H+modifier and DEBC with H+concordance between control and LBP group. The study determined the risk of LBP patients undergoing surgery as well as the incidence of postoperative infection based on DEBC changes. Significance was calculated by binomial test and chi-square test with the effect size of 0.3 to 0.5. Prevalence and association of outcome were calculated by Altman's odds ratio with the 95% CI and the scoring of z statistics. Logistic expression was plotted for independent variables associated with each class of both Modic and DEBC against dependent variables surgery and nonsurgery. METHODS: Lumbar segments in both groups were assessed for MC types. The DEBC classification was developed with the addition of STIR images and studying the interdependent complex as a whole: type-A: acute inflammation; type-B: chronic persistence; type-C: latent and type-D: inactive. Modifier H+ was added if there was disc herniation. The classification was compared with MC and correlated to clinical outcomes. RESULTS: A total of 3,560 EPs of 445 controls and 8,680 EPs in 1,085 patients with LBP were assessed. Four nonMC, 560 MC-II, and 22 MC-III EPs were found to have previously undetected edema in STIR (n=542) or hyperintensity in discs (n=44) needing reclassification. The formerly undescribed type-B of DEBC, representing a chronic persistent activity state was the most common (51.8%) type. The difference between the control and LBP of H+(12% vs 28.8%) and its co-occurrence with DEBC type 1.1% vs 23.3%) was significant (p<.0001). The odds ratio for the need for surgery was highest (OR=5.2) when H+ and DEBC type change co-occurred. Postoperative deep infection (as determined by CDC criteria) was 0.47% in nonDEBC, compared with 2.4% in patients with DEBC (p=.002), with maximum occurrence in type-B. CONCLUSION: Classification based on the classic MC was found to need a reclassification in 586 EPs showing the shortcomings of results of previous studies. Considering the DEBC allowed better classification and better predictability for the need for surgical intervention and incidence of postoperative infection rate than MC.

Abdominal Fat is a Reliable Indicator of Lumbar Intervertebral Disc Degeneration than Body Mass Index.

OBJECTIVE: The objective of this study was to determine whether abdominal fat status correlates with low back pain (LBP) and lumbar intervertebral disc degeneration (IVDD) and to identify a new anthropometric index to predict the likelihood of developing LBP. METHODS: Patients with chronic low back pain admitted to the Affiliated Hospital of Southwest Medical University from June 2022 to May 2023 were collected as the experimental group. Volunteers without LBP from June 2022 to May 2023 were also recruited as the control group. They underwent lumbar spine magnetic resonance imaging and had their body mass index (BMI) measured. Abdominal parameters were measured on T2-weighted median sagittal magnetic resonance imaging at the L3/4 level: abdominal diameter, sagittal abdominal diameter (SAD), and subcutaneous abdominal fat thickness (SAFT). Each lumbar IVDD was assessed using the Pfirrmann grading system. The differences in abdominal parameters and BMI between the experimental and control groups were compared, and the correlations between abdominal parameters, BMI, LBP, and IVDD were analyzed. RESULTS: Abdominal diameter, SAD, and SAFT had moderate-to-strong correlations with BMI. SAD was significantly associated with severe IVDD at L4-L5 and L5-S1 levels with odds ratio of 3.201 (95% confidence interval [CI]: 1.850-5.539, P < 0.001) and 1.596 (95% CI: 1.072-2.378, P = 0.021), respectively. BMI had no significant association with severe IVDD. In women, SAFT and BMI were significantly correlated with LBP; in men, only SAFT was significantly correlated with LBP. Appropriate cutoff values for men and women were 1.52 cm (area under the curve = 0.702, 95% CI: 0.615-0.789, P < 0.001) and 1.97 cm (area under the curve = 0.740, 95% CI: 0.662-0.818, P < 0.001), respectively. Men and women with SAFT of >1.52 cm and >1.97 cm, respectively, had significantly higher rates of LBP. CONCLUSIONS: SAD could predict severe IVDD better than BMI. SAFT is a better predictor of LBP than BMI, especially in men, and reliably distinguished patients with LBP from asymptomatic subjects with reliable cutoff values for men and women.

The effect of lumbosacral transitional vertebra on lumbar spine degeneration and spondylolisthesis among patients with low back pain.

AIM: To examine the impact of lumbosacral transitional vertebra (LSTV) on lumbar spine degeneration, disc protrusion, and spondylolisthesis among patients with low back pain. METHODS: The records of the patients who had undergone anterioposterior lumbar radiographs and lumbar magnetic resonance imaging (MRI) for low back pain between November 2014 and September 2021 were extracted retrospectively and assessed for eligibility. Of the remaining patients, those with LSTV were assigned as "case group." Age- and sex-matched patients without LSTV were assigned as "control group." On digitalized lumbar MRIs, Modic degeneration (type I-III) and Pfirrman's disc degeneration (grade I-V) immediately cephalad to the transitional level were evaluated; intervertebral disc height (mm), disc protrusion (mm), and percentage of vertebral slippage (%) were measured. RESULTS: Of the 501 patients with low back pain, 128 ineligible patients were excluded; 113 patients with LSTV and 117 age- and sex-matched controls were included in the study. LSTV group revealed decreased intervertebral disc height, increased vertebral endplate degeneration, and slippage, as well as increased disc degeneration and protrusion when compared with controls (p < 0.001). Patients with type III LSTV had greater disc protrusion and higher percentage of slippage compared to those with type I LSTV (p = 0.008 and p = 0.009, respectively). Vertebral endplate degeneration, disc height, and disc degeneration did not differ across categories of LSTV type. CONCLUSION: Lumbosacral transitional vertebra malformation is related to decreased intervertebral disc height, increased disc degeneration, vertebral endplate degeneration, disc protrusion, and slippage above the level of transition. Patients with type III LSTV revealed the highest percentage of slippage and disc protrusion.

Hydrogel Augmentation of the Lumbar Intervertebral Disc: An Early Feasibility Study of a Treatment for Discogenic Low Back Pain.

PURPOSE: To assess the safety and effectiveness of intradiscal hydrogel in patients with chronic low back pain (CLBP) due to degenerative disc disease (DDD) refractory to conventional medical management. MATERIALS AND METHODS: Twenty patients aged 22-69 years with numerical rating scale (NRS) pain of ≥4 were enrolled. All patients with CLBP resulting from DDD confirmed by imaging and discography received injections of hydrogel (Hydrafil Intervertebral Disc Augmentation; ReGelTec, Baltimore, Maryland) at 1 or 2 lumbar levels (29 levels treated) from August to December 2020. The primary safety end point was freedom from serious adverse events (SAEs). The primary performance end point was successful gel delivery into the desired disc. Patients were also assessed on the NRS as well as the Oswestry disability index (ODI). RESULTS: Nineteen patients were followed up at a mean of 131 days, and 1 patient was lost to follow-up. Preliminary results showed significant reductions in median NRS back pain from 7 (range 4-10) to 1 (range 0-8) (P <.0001) and median ODI scores from 54 (range 22-58) to 2 (range 0-58) (P <.0001) at 6 months of follow-up. There were 5 SAEs, and 4 of the 2 were determined to be associated with treatment. CONCLUSIONS: This early feasibility study showed that the hydrogel implant was safe with no persistently symptomatic SAEs, and demonstrated effectiveness with significant reduction in pain and improvement in function when used to treat painful DDD and CLBP.

Management Considerations for Total Intervertebral Disc Replacement.

The burden of disease regarding lumbar and cervical spine pain is a long-standing, pervasive problem within medicine that has yet to be resolved. Specifically, neck and back pain are associated with chronic pain, disability, and exorbitant health care use worldwide, which have only been exacerbated by the increase in overall life years and chronic disease. Traditionally, patients with significant pain and disability secondary to disease of either the cervical or lumbar spine are treated via fusion or discectomy. Although these interventions have proved curative in the short-term, numerous longitudinal studies evaluating the efficacy of traditional management have reported severe impairment of normal spinal range of motion, as well as postoperative complications, including neurologic injury, radiculopathy, osteolysis, subsidence, and infection, paired with less than desirable reoperation rates. Consequently, there is a call for innovation and improvement in the treatment of lumbar and cervical spine pain, which may be answered by a modern technique known as intervertebral disc arthroplasty, or total disc replacement (TDR). Thus, this review aims to describe the management strategy of TDR and to explore updated considerations for its use in practice, both to help guide clinical decision making.

Fatty infiltration of the erector spinae at the upper lumbar spine could be a landmark for low back pain.

PURPOSE: Intervertebral disc degeneration (IVDD), Modic changes, and fatty infiltration in the paraspinal muscles are possible causes of low back pain (LBP). Multifidus has been the most commonly blamed paraspinal muscle in the etiology of LBP. However, it contributes to 20% of the extensor moment on the lumbar spine. In the present study, we aimed to identify whether patients with LBP and asymptomatic subjects differed in terms of intervertebral discs, end-plates, and fatty infiltration in their paraspinal muscles. METHODS: Consecutive women and men, who visited the spine outpatient clinics with chronic LBP and had lumbar spine MRI for their LBP without leg pain were included. Asymptomatic subjects without LBP/leg pain for the last year were recruited. Modic changes, IVDD, and fatty infiltration in the paraspinal muscles were evaluated on lumbar spine magnetic resonance imagings of the patients with LBP and age-, gender- and BMI-matched asymptomatic controls. RESULTS: Low back pain was closely associated with fatty infiltration in the paraspinal muscles at all lumbar levels whereas it had association with severe IVDD and Modic changes at lower lumbar levels. Multifidus at the lower lumbar levels was the fattiest paraspinal muscle in both asymptomatic subjects and patients with LBP. Patients with LBP had severe fatty infiltration in the erector spinae at the upper lumbar levels. CONCLUSION: Severe IVDD and Modic changes were more common at lower lumbar levels in patients with LBP. Both asymptomatic subjects and those with LBP had fatty multifidus at lower lumbar levels, whereas those with LBP had fatty infiltration in the erector spinae at upper lumbar levels. We suggest that fatty infiltration could have started in the multifidus. The erector spinae had greater contribution to the lumbar extension compared to the multifidus. Thus, LBP could develop when the quality of the erector spinae at the upper lumbar levels impairs due to fatty infiltration.

Identifying clusters of objective functional impairment in patients with degenerative lumbar spinal disease using unsupervised learning.

OBJECTIVES: The five-repetition sit-to-stand (5R-STS) test was designed to capture objective functional impairment (OFI), and thus provides an adjunctive dimension in patient assessment. It is conceivable that there are different subsets of patients with OFI and degenerative lumbar disease. We aim to identify clusters of objectively functionally impaired individuals based on 5R-STS and unsupervised machine learning (ML). METHODS: Data from two prospective cohort studies on patients with surgery for degenerative lumbar disease and 5R-STS times of ≥ 10.5 s-indicating presence of OFI. K-means clustering-an unsupervised ML algorithm-was applied to identify clusters of OFI. Cluster hallmarks were then identified using descriptive and inferential statistical analyses. RESULTS: We included 173 patients (mean age [standard deviation]: 46.7 [12.7] years, 45% male) and identified three types of OFI. OFI Type 1 (57 pts., 32.9%), Type 2 (81 pts., 46.8%), and Type 3 (35 pts., 20.2%) exhibited mean 5R-STS test times of 14.0 (3.2), 14.5 (3.3), and 27.1 (4.4) seconds, respectively. The grades of OFI according to the validated baseline severity stratification of the 5R-STS increased significantly with each OFI type, as did extreme anxiety and depression symptoms, issues with mobility and daily activities. Types 1 and 2 are characterized by mild to moderate OFI-with female gender, lower body mass index, and less smokers as Type I hallmarks. CONCLUSIONS: Unsupervised learning techniques identified three distinct clusters of patients with OFI that may represent a more holistic clinical classification of patients with OFI than test-time stratifications alone, by accounting for individual patient characteristics.

Intervertebral disc human nucleus pulposus cells associated with back pain trigger neurite outgrowth in vitro and pain behaviors in rats.

Low back pain (LBP) is often associated with the degeneration of human intervertebral discs (IVDs). However, the pain-inducing mechanism in degenerating discs remains to be elucidated. Here, we identified a subtype of locally residing human nucleus pulposus cells (NPCs), generated by certain conditions in degenerating discs, that was associated with the onset of discogenic back pain. Single-cell transcriptomic analysis of human tissues showed a strong correlation between a specific cell subtype and the pain condition associated with the human degenerated disc, suggesting that they are pain-triggering. The application of IVD degeneration-associated exogenous stimuli to healthy NPCs in vitro recreated a pain-associated phenotype. These stimulated NPCs activated functional human iPSC-derived sensory neuron responses in an in vitro organ-chip model. Injection of stimulated NPCs into the healthy rat IVD induced local inflammatory responses and increased cold sensitivity and mechanical hypersensitivity. Our findings reveal a previously uncharacterized pain-inducing mechanism mediated by NPCs in degenerating IVDs. These findings could aid in the development of NPC-targeted therapeutic strategies for the clinically unmet need to attenuate discogenic LBP.

Comparison of the effectiveness of zero-profile device and plate cage construct in the treatment of one-level cervical disc degenerative disease combined with moderate to severe paraspinal muscle degeneration.

Objective: Recent evidence indicates that cervical paraspinal muscle degeneration (PMD) is a prevalent and age-related condition in patients with cervical disc degenerative disease (CDDD). However, the relationship between surgery selection and post-operative outcomes in this population remains unclear. Consequently, this study aims to investigate the disparities in clinical outcomes, radiological findings, and complications between two frequently utilized anterior cervical surgical procedures. The objective is to offer guidance for the management of PMD in conjunction with CDDD. Methods: A total of 140 patients who underwent single-level anterior cervical discectomy and fusion (ACDF) at our department were included in this study. The patients were divided into three groups based on the severity of PMD: mild (n=40), moderate (n=54), and severe (n=46), as determined by Goutalier fat infiltration grade. The subjects of interest were those with moderate-severe PMD, and their clinical outcomes, radiological parameters, and complications were compared between those who received a stand-alone zero-profile anchored cage (PREVAIL) and those who received a plate-cage construct (PCC). Results: The JOA, NDI, and VAS scores exhibited significant improvement at all postoperative intervals when compared to baseline, and there were no discernible differences in clinical outcomes between the two groups. While the PCC group demonstrated more pronounced enhancements and maintenance of several sagittal alignment parameters, such as the C2-7 angle, FSU angle, C2-7 SVA, and T1 slope, there were no statistically significant differences between the two groups. The incidence of dysphagia in the zero-profile group was 22.41% at one week, which subsequently decreased to 13.79% at three months and 3.45% at the final follow-up. In contrast, the plate cage group exhibited a higher incidence of dysphagia, with rates of 47.62% at one week, 33.33% at three months, and 11.90% at the final follow-up. Notably, there were significant differences in the incidence of dysphagia between the two groups within the first three months. However, the fusion rate, occurrence of implant subsidence, and adjacent segment degeneration (ASD) were comparable at the final follow-up. Conclusion: For patients with one-level cervical disc degenerative disease combined with paraspinal muscle degeneration, both the zero-profile technique and PCC have demonstrated efficacy in ameliorating clinical symptoms and maintaining the postoperative sagittal balance. Although no significant disparities were observed between these two technologies in terms of complications such as adjacent segment degeneration and implant subsidence, the zero-profile technique exhibited superior performance over PCC in relation to dysphagia during the early stages of postoperative recovery. To validate these findings, studies with longer follow-up periods and evaluations of multilevel cervical muscles are warranted.

Ultrasound-guided disc pain induction test for diagnosis of discogenic lumbar pain: a cross-sectional study.

BACKGROUND: Several methods can be used to diagnose discogenic pain, but only discoblock can diagnose discogenic pain definitively. This study aimed to examine the usefulness of an ultrasound-guided disc pain induction test for a simple and accurate diagnosis of the culprit lesion. METHODS: We included 41 patients with lumbar pain in whom pain was induced by an ultrasound-guided disc pain induction test. All patients had confirmed pain at L1/2 to L5/S1 based on an ultrasound-guided disc pain induction test and underwent X-ray photography and magnetic resonance imaging. Seventeen patients who required injection due to severe pain underwent discoblock procedures for discs with the most intense pain, and visual analogue scale (VAS) scores were obtained before and after the procedure for these patients. We analysed the association between painful discs and radiological findings. RESULTS: Pain induction was noted in a total of 65 discs, and the pain was induced in 23 patients in only one disc. All patients had disc degeneration of Pfirrmann classification grade 1 or higher, with more significant disc degeneration in painful discs than in painless discs. There was no significant relationship between the presence or absence of pain and Modic type. The average VAS measurements improved significantly from 9.5 (pre-procedure) to 2.5 (post-procedure). These results suggest that the most painful discs were the causes of discogenic lumbar pain. CONCLUSIONS: Our ultrasound-guided disc pain induction test may help diagnose disc degeneration and identify culprit lesions, even when multiple discs exhibit findings of degeneration.