Despite the clinical relevance of back pain and intervertebral disc herniation, the lack of reliable models has strained their molecular understanding. We characterized the lumbar spinal phenotype of C57BL/6 and SM/J mice during aging. Interestingly, old SM/J lumbar discs evidenced accelerated degeneration, associated with high rates of disc herniation. SM/J AF's and degenerative human's AF transcriptomic profiles showed altered immune cell, inflammation, and p53 pathways. Old SM/J mice presented increased neuronal markers in herniated discs, thicker subchondral bone, and higher sensitization to pain. Dorsal root ganglia transcriptomic studies and spinal cord analysis exhibited increased pain and neuroinflammatory markers associated with altered extracellular matrix regulation. Immune system single-cell and tissue level analysis showed distinctive T-cell and B-cell modulation and negative correlation between mechanical allodynia and INF-α, IL-1β, IL2, and IL4, respectively. This study underscores the multisystemic network behind back pain and highlights the role of genetic background and the immune system in disc herniation disease. Acknowledgments: This study is supported by grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) R01AR055655, R01AR064733, R01AR074813 to MVR

Abstract. Objectives. There is still controversy in the literature over whether Cervical Foraminotomy or Anterior Cervical discectomy and fusion (ACDF) is best for treating cervical Radiculopathy. Numerous studies have focused on the respective complication rates of these procedures and outcome measures with a lack of due consideration to preoperative MRI findings. Proximal foraminal stenosis can theoretically be accessed via either approach. We aimed to investigate whether patient reported outcome measures (PROMs) favoured one approach over the other in patients with proximal foraminal stenosis. Methods. A single centre retrospective review of patients undergoing either ACDF or Cervical foraminotomy over the period 2012 to 2022. VAS, Neck disability index (NDI), EQ5DL and Patient Satisfaction on a Five Point Likert scale were obtained. Patients who had both an ACDF and a Foraminotomy were excluded. Axial MRI images were analysed and the location of the worst clinically relevant disc herniation stratified as follows: Central (1), Paracentral (2) and Foraminal (3). Correlations and average PROMs were analysed in SPSS. Results. PROMs scores were available for 33 ACDF patients and 37 Foraminotomy patients. Average surgery time in ACDF group was 167 minutes while Foraminotomy 142 minutes. Average Length of hospital stay was 6.24 days in the Foraminotomy group and 3.54 days in the ACDF group. 18 patients were excluded due to having both surgeries (2 of which developed CSF leaks postoperatively). Of the included patients there were no postoperative complications. 13 patients in the ACDF had Central or Paracentral stenosis in addition to proximal Foraminal stenosis, 3 patients in the Foraminotomy group had some significant Paracentral herniation just before the Proximal foramen. The majority of patients in both groups had pure proximal Foraminal stenosis (N= 17 (ACDF), 20 (Foraminotomy). The results showed no significant difference in PROMs between patients who received an ACDF or a Foraminotomy for Proximal foraminal stenosis (EQ5DL, NDI, and satisfaction, P= 0.268, 0.253 and 0.327). There was no correlation between location of the stenosis and PROM scores in either group. Conclusions. Our data suggest that Proximal foraminal stenosis can be effectively addressed by either an anterior ACDF or a Foraminotomy with no difference in complication rates. Foraminotomy has the benefit of no implant cost but longer hospital stay. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

With the increase in the elderly population, there is a dramatic increase in the number of spinal fusions. Spinal fusion is usually performed in cases of primary instability. However it is also performed to prevent iatrogenic instability created during surgical treatment of spinal stenosis in most cases. In literature, up to 75% of adjacent segment disease (ASD) can be seen according to the follow-up time. 1. Although ASD manifests itself with pathologies such as instability, foraminal stenosis, disc herniation or central stenosis. 1,2. There are several reports in the literature regarding lumbar percutaneous transforaminal endoscopic interventions for lumbar foraminal stenosis or disc herniations. However, to the best our knowledge, there is no report about the treatment of central stenosis in ASD. In this study, we aimed to investigate the short-term results of unilateral biportal endoscopic decompressive laminotomy (UBEDL) technique in ASD cases with symptomatic central or lateral recess stenosis. The number of patients participating in the prospective study was 8. The mean follow-up was 6.9 (ranged 6 to 11) months. The mean age of the patients was 68 (5m, 3F). The development of ASD time after fusion was 30.6 months(ranged 19 to 42). Mean fused segments were 3 (ranged 2 to 8). Preoperative instability was present in 2 of the patients which was proven by dynamic lumbar x-rays. Preoperative mean VAS-back score was 7.8, VAS Leg score was 5.6. The preoperative mean JOA (Japanese Orthopaedic Association) score was 11.25. At 6th month follow-up, the mean VAS back score of the patients was 1, and the VAS leg score was 0.5. This improvement was statistically significant (p = 0.11 and 0.016, respectively). The mean JOA score at the 6th month was 22.6 and it was also statistically significant comparing preoperative JOA score(p = 0.011). The preoperative mean dural sac area measured in MR was 0.50 cm2, and it was measured as 2.1 cm. 2. at po 6 months.(p = 0.012). There was no progress in any patient's instability during follow-up. In orthopedic surgery, when implant related problems develop in any region of body (pseudoarthrosis, infection, adjacent fracture, etc.), it is generally treated by using more implants in its final operation. This approach is also widely used in spinal surgery. 3. However, it carries more risk in terms of devoloping ASD, infection or another complications. In the literature, endoscopic procedures have almost always been used in the treatment of ventral pathologies which constitute only 10%. In ASD, disease devolops as characterized by wide facet joint arthrosis and hypertrophied ligamentum flavum in the cranial segment and it is mostly presented both lateral recess and santal stenosis symptoms (39%). In this study, we found that UBEDL provides successful results in the treatment of patients without no more muscle and ligament damage in ASD cases with spinal stenosis. One of the most important advantages of UBE is its ability to access both ventral and dorsal pathologies by minimally invasive endoscopic aproach. I think endoscopic decompression also plays an important role in the absence of additional instability at postoperatively in patients. UBE which has already been described in the literature given successful results in most of the spinal degenerative diseases besides it can also be used in the treatment of ASD. Studies with longer follow-up and higher patient numbers will provide more accurate results

Background. Recently, some studies have focused attention on the possibility that anaerobic pathogens of low virulence could constitute an etiological factor in disc herniation. There have been isolated such strains, predominantly Propionibacterium acne, between 7 and 53% of patients undergoing surgery for disc pathology. According to these studies, patients with anaerobic infections of the disc are more likely to develop Modic changes in the adjacent vertebrae. The aim of this work was to test this hypothesis by growing in specific media the disc material extracted in a series of lumbar discectomy and relating this factor with the presence of pre-intervention Modic changes. Methods. A total of 22 consecutive patients undergoing primary unisegmental discectomy for lumbar disc herniation (77.2% male, mean age 40.1 ± 9.1 years) were included. All patients were immunocompetent and none had previously received an epidural steroid injection prior surgery. MRI study confirmed the disc herniation. Following strict antiseptic protocols, the extracted disc material was sent for slow-growth anaerobic enriched culture (>10 days). Results. In total, anaerobic cultures were positive in 7 cases (31.8%) all men. In 5 of these cases, the symptoms developed with an acute onset. The isolated germs were always unique: Propionibacterium acne (3), Streptococcus parasanguinis (1), Actinomyces naeslundii (1), Actinomyces meyeri (1) and methicillin sensitive Staphylococcus epidermidis. Only two (28.6%) of these 7 patients had Modic changes on MRI prior surgery (one type I, one type 2). None of the patients with negative cultures had Modic changes. Conclusions. These findings support the theory that anaerobic infections of low virulence and slow growth may contribute to the pathogenesis of herniated discs. However, these cases do not necessarily develop type 1 Modic changes as previously speculated. Level of evidence. Level IV

Purpose of the Study. Assessment of long term results of Chemonucleolysis vs. surgery for soft disc herniation. Material and Methods. From 1982 to 1985, 100 patients with symptomatic disc herniation were randomly allocated to receive either Chemonucleolysis(48) or surgery(52) after a three months trial of conservative treatment. Ten of the chemonucleolysis had surgery. At 10–13 year follow up, Sixty one of the original 100 patients responded, (32 chemonucleolysis; 29 surgery). At 25–27 year Forty four patients responded (24 chemonucleolysis; 20 surgery). Clinical outcome at one year was according to a self-assessment questionnaire: Completely, better improved, the same, or worse, and at the later follow up periods, according to the Macnab criteria. The results of two groups of patients were compared using Chi square and T test for independent samples. The disc height of the affected disc was measured from the lateral lumbar spine radiograph taken pre-operatively, and at the later two time points, and compared to a normal adjacent disc expressed as a percentage. Results. The intent to treat clinical outcome results showed a high success rate at one year (93% chemonucleolysis; 96% surgery completely better or improved); and also at the later two time points with no significant difference between the groups. The radiological data showed no difference in disc height between the groups at any of the time points with some reduction over time with aging. Conclusion. There is no difference between the groups in either clinical or radiological outcome over time. Chymopapain, presently not widely available, should be made available again. No conflict of interest. No funding obtained. This abstract has not been previously published in whole or substantial part nor has it been presented previously at a national meeting

Introduction. In degenerative disorders of the spine such as disc herniation, intervertebral discs can affect neural tissue, which may result in pain as demonstrated in both basic science and clinical investigations. Previous in vitro and in vivo studies have shown that notochordal cells and chondrocyte-like cells in nucleus pulposus affect nervous tissue differently. The aim of the present study was to evaluate the morphology of spinal neural tissue in an in vivo rat model following application of cells derived from nucleus pulposus. Material and method. A disc herniation model in rats (n=58) was used. The L4 nerve root was exposed to a) nucleus pulposus (3mg), b) notochordal cells (25,000 cells) or c) chondrocyte-like cells (25,000 cells). Four control groups were included: 1) application of nucleus pulposus (3 mg) and mechanical displacement of the spinal nerve complex, 2) sham operated animals, 3) application of cell diluent (50 μl) and 4) naïve animals. Seven days after surgery the L4 nerve roots with their dorsal root ganglion were harvested and prepared for blinded neuropathological examinations using light microscopy. Results. Damage and loss of myelinated nerve fibers as well as epineural granulation tissue were most pronounced in the group that had been subjected to nerve root displacement and application of nucleus pulposus. There was significantly less nerve fiber damage in all other groups. The number of myelinated nerve fibers with enlarged outer Schwann cell compartment was significantly higher in all experimental groups as compared to naïve animals, except for animals in which the nerve root complex had been exposed to cell diluent, notochordal cells and chondrocyte-like cells. Discussion and Conclusion. This is the first examination nerve root and dorsal root ganglion morphology after exposure to notochordal cells and chondrocyte-like cells in an in vivo model. The results indicate that application of notochordal cells and chondrocyte-like cells, per se, do not structurally affect the myelinated nerve fibers compared to naïve animals. However, one cannot exclude that there may be physiological effects of notochordal cells and chondrocyte-like cells on nerve tissue in vivo although no morphological differences were observed with the present method. The findings in the present study support previous observations that mechanical nerve tissue displacement and application of nucleus pulposus can induce pronounced morphological nerve tissue changes. However, the combination of mechanical nerve tissue displacement and application of notochordal cells and/or chondrocyte-like cells was not tested. In conclusion, the present study suggests that mechanical nerve tissue displacement is a prerequisite for the induction of morphological changes following application of disc tissue and its components on neural tissue. Summary. The effects of notochordal cells and chondrocyte-like cells on spinal nerve tissue might be dependent on concurrent mechanical nerve tissue deformation

Summary Statement. Repetitive loading of degenerated human intervertebral discs in combined axial compression, flexion and axial rotation, typical of manual handling lifing activities, causes: an increase in intradiscal maximum shear strains, circumferential annular tears and nuclear seperation from the endplate. Introduction. Chronic low back pain (LBP) is a crippling condition that affects quality of life and is a significant burden to the health care system and the workforce. The mechanisms of LBP are poorly understood, however it is well known that loss of intervertebral disc (disc) height due to degeneration is a common cause of chronic low back and referred pain. Gross disc injury such as herniation can be caused by sudden overload or by damage accumulation via repetitive loading, which is a cause of acute LBP and an accelerant of disc degeneration. The aim of this study was to determine for the first time the relationship between combined repetitive compression, flexion and axial rotation motion of degenerated cadaver lumbar spine segments, and the progression of three-dimensional (3D) internal disc strains that may lead to disc herniation and macroscopic tissue damage. Patients & Methods. Seven degenerated human lumbar functional spinal units (FSUs) underwent pre-test MRI, had a grid of tantalum wires inserted into the mid-transverse plane of the disc and were subjected to 20,000 cycles of repetitive loading in combined compression (1.7 MPa), flexion (11–13°) and right axial rotation (2–3°) in a six degree of freedom hexapod robot. Stereoradiographs were taken at cyclic intervals (1, 500, 1000, 5000, 10000, 15000 and 20000 cycles) from which 3D intradiscal principal strains and maximum shear strains (MSS) were calculated and partitioned into nine disc anatomical regions. After testing the discs underwent post-test MRI followed by macroscopic assessment to identify tissue damage. A repeated measures ANOVA having a within-subjects factor of cycle number, and a between-subjects factor of disc region was used to examine the effects of cycle number and disc region on MSS. Results. No visible evidence of disc herniation occurred after 20,000 cycles, however circumferential annular tears and nucleus separation from the endplate were observed in all specimens in agreement with observed signal changes in post-test MRI images. There was a significant effect of both cycle number, disc region and the interaction of cycle number x disc region on MSS (p<0.001). MSS was significantly larger after 20,000 cycles compared with the first loading cycle in the anterior, left anterolateral, left lateral, and left posterolateral disc regions (p<0.037). Minor changes in MSS were seen in the posterior and nucleus regions. The largest increases were observed in the left anterolateral and left posterolateral regions after 20,000 cycles. Discussion/Conclusion. A significant increase in MSS was observed across most regions in the disc after 20,000 repetitive loading cycles, especially in the left anterolateral and left posterolateral regions. No herniation was observed, although macroscopic and MRI evidence of circumferential annular tears and nuclear separation from the endplate occurred, suggesting internal disc tissue disorganisation that may indicate a progression towards eventual herniation

Introduction. Risk factors for disc degeneration depend on how the condition is defined, i.e. on the specific disc degeneration “phenotype”. We present evidence that there are two major and largely-distinct types of disc degeneration. Methods. The relevant research literature was reviewed and re-interpreted. Evidence. In the . upper. lumbar and thoracic spine, disc degeneration is closely associated with endplate defects and with inflammatory changes in the vertebral bodies. It has a relatively high heritability (i.e. a strong genetic influence), and its incidence does not increase markedly with age. In the . lower. lumbar spine, disc degeneration is closely associated with radial fissures and nucleus herniation. Here it has a relatively low heritability, and a correspondingly stronger association with mechanical loading, and its incidence increases steadily throughout life. Mechanical experiments on cadaveric spines show that endplate fracture and nucleus herniation can be caused by compressive loading, and by bending combined with compression, respectively. Both lesions cause an immediate decompression of the nucleus, so that it becomes difficult to create subsequently the other lesion in the same disc. This suggests distinct phenotypes. Interpretation. The two types of disc degeneration are not entirely distinct, because disc herniation sometimes occurs at upper lumbar levels. Nevertheless, it may be useful to recognise two phenotypes when it comes to explaining and treating discogenic pain. Some other common disc changes (such as water loss and bulging) are attributable to ageing rather than degeneration, whereas disc narrowing probably represents a final common pathway for both types of disc degeneration. Conflicts of Interest. None. Source of Funding. None. This abstract has not been previously published in whole or in part; nor has it been presented previously at a national meeting

Introduction. Discogenic pain is associated with ingrowth of blood vessels and nerves, but uncertainty over the extent of ingrowth is hindering development of appropriate treatments. We hypothesise that adult human annulus fibrosus is such a dense crosslinked tissue that ingrowth via the annulus is confined to a) peripheral regions, and b) fissures extending into the annulus. Methods. Disc tissue was examined from 61 patients (aged 37–75 yrs) undergoing surgery for disc herniation, degeneration or scoliosis. 5 µm sections were stained with H&E to identify structures and tissue types. 30 µm frozen sections were examined using confocal microscopy, following immunostaining for CD31 (an endothelial cell marker), PGP 9.5 and Substance P (general and nociceptive nerve markers, respectively). Fluorescent tags were attached to the antibodies. ‘Volocity’ software was used to calculate numbers and total cross-sectional area of labelled structures, and to measure their distance from the nearest free surface (disc periphery, or annulus fissure). Results. Maximum penetration of blood vessels and nerves from the peripheral annulus was 4,800 µm and 2,200 µm respectively. Maximum distance of nerves and vessels from the nearest free surface was 236 µm and 888 µm. Substance P (but not PGP 9.5) was co-localised with blood vessels, and both number and area of Substance P-stained structures were inversely correlated with grade of disc degeneration. Interpretation. Thick sections and fluorescent markers can show reliably where labelled structures are not present. Results therefore support our hypothesis: deep penetration of nerves into the human annulus occurs only if fissures are present. No conflicts of interest. No funding obtained. This abstract has not been previously published in whole or in part; nor has it been presented previously at a national meeting

Introduction. Herniated disc tissue removed at surgery usually appears degenerated, and MRI often reveals degenerative changes in adjacent discs and vertebrae. This has fostered the belief that a disc must be degenerated before it can herniate, which has medicolegal significance. We hypothesise that degenerative changes in herniated disc tissues differ from those found in tissues that have degenerated in-situ, and are consistent with being consequences rather than causes of herniation. Methods. Surgically-removed discs were examined using histology, immunohistochemistry and confocal microscopy. 21 samples of herniated tissues were compared with age-matched tissues excised from 11 patients whose discs had reached a similar Pfirrman grade of degeneration but without herniating. Degenerative changes were assessed separately in three tissue types (where present): nucleus, inner annulus, and outer annulus. Mann-Whitney U tests were used to compare ‘herniated’ vs ‘in-situ’ tissues. Results. Herniated tissues showed significantly greater cellularity (annulus), greater proteoglycan loss (outer annulus), greater neovascularisation (annulus), greater innervation (annulus) as judged by PGP 9.5 staining, greater expression of matrix-degrading enzymes MMP1 and MMP3 (inner annulus), but less cell clustering (outer annulus). Some similar but non-significant differences were seen in nucleus tissues. Interpretation. Herniated tissues that escape the pressurised confines of the disc are free to swell, lose proteoglycans and come into contact with blood cells. These events could explain most of the differences between herniated tissues and those that degenerated ‘in situ’. Results support our hypothesis, and warn against assuming that degenerative changes always precede (or cause) disc herniation. No conflicts of interest. No funding obtained. This abstract has not been previously published in whole or in part; nor has it been presented previously at a national meeting

Introduction. Recently various type of spinal instrumentation was applied, and they are essential in modern spinal fusion surgery. Whereas several authors reported increased possibility of complication and degeneration on adjacent segment. We tried PLIF without instrumentation with box type intervertebral cages. Method. Forty-one cases of degenerative lumbar diseases were treated by PLIF with carbon cages without spinal instrumentation. There were 17 males and 24 females, and age averaged 71.4 years. Thirty-two cases were degenerative spondylolisthesis, five were spinal stenosis, and four were disc herniation. Single PLIF was performed on forty cases, and double segment in one, with additional decompression on other segment in twenty. Bilateral facet joint were preserved to avoid lateral instability. Two pieces of cage were inserted with local bone graft. Post-op. follow-up period were 12 to 24 months, 15 months on average. Result. JOA score (29 pts on full mark) averaged 12.7 pts before the operation and was 25.4 pts at the F/U. Recovery ratio averaged 77.9%. Clinical result was excellent in 27 with more than 75% of R/R. One case showed symptomatic non-union, and additional instrumentation was applied after one year. Thirty-three cases (80%) showed solid bone union after one year, and eight cases were classified as non-union. Whereas early cage migration with vertebral collapse was seen on fourteen, and union with collapse was seen in eight. These conditions showed less clinical outcome. Conclusion. Stand alone PLIF resulted in good clinical results with box type cages. Stand alone PLIF is less invasive method and minimize chance of complication. Conflicts of interest. None. Sources of funding. None