Background and purpose of study:. Chronic back pain is a complex and poorly understood condition incorporating sensory, cognitive and emotional elements. Research demonstrates a strong association between chronic back pain and cognitive and non-cognitive factors such as anxiety, depression, fear-avoidance and self-efficacy. However, until very recently, the way in which chronic back pain sufferers process their emotions was largely unknown. To this end, we conducted two case-control studies using a between-groups correlational design to investigate the relationship between chronic back pain and emotional processing. Methods and results:. In study 1, 55 chronic back pain sufferers and 55 pain-free individuals were administered the Emotional Processing Scale (EPS) to determine whether chronic back pain sufferers process their emotions differently from pain-free individuals. In study 2, 32 CBP sufferers and 27 pain-free individuals were administered the EPS, PHQ-9 and the GAD-7 to further test if chronic back pain is associated with altered emotional process and whether anxiety and depression may play a role in this relationship. Conclusion:. Our studies demonstrate that altered emotional processing and regulation are strongly associated with chronic back pain. Prospective studies are necessary before it can be ascertained whether this relationship is causative or as a consequence of chronic back pain. However, our results are in line with a recent prospective neuroimaging study, which demonstrates that chronification of low back pain shifts brain representation from nociceptive to emotional circuits. It is therefore critical that clinicians in the field of musculoskeletal care consider the role of emotional processing in their patients' evaluation and management

Background. Chronic back pain (CBP) is a major cause of disability globally and its causes are multifactorial. Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) are human herpes viruses usually acquired in early life. About 50% and over 90% of the population worldwide have been infected with CMV and EBV, respectively. This study investigated a potential causal relationship between CMV infection and CBP. Method. UK Biobank participants provided information on CMV seropositivity and CBP status, which were available for both traits in 5,140 participants. We used EBV seropositivity as a negative control to identify confounding and inaccurate causal inference. A one-sample Mendelian randomization (MR) based on independent genetic variants predicting CMV and EBV positivity was conducted in Northern European participants. To validate the association further, the MR study was repeated using a CMV polygenic risk score (PRS). Results. CMV GWAS revealed 86 independent SNPs having p-value < 2 × 10. −4. for the one-sample MR. These SNPs were used to define genetically-predicted categories of CMV infection risk. CMV infection risk categories were significantly associated with CBP (OR = 1.150; 95% CI: 1.005–1.317, p-value = 0.043), findings which were confirmed using the CMV PRS (OR = 1.299; 95% CI: 1.141–1.479, p-value = 0.001). There was no causal association between EBV and CBP (p-value = 0.17). Conclusion. Our results provide further evidence for a causal relationship between CMV infection and CBP. These results suggest a stratified approach to CBP may be useful, particularly in clinical trials and they shed light on underlying mechanisms in CBP. Conflicts of interest. No conflicts of interest. Sources of funding. No funding obtained. Acknowledgement. UKBB data were obtained under the project #18219. Some aspects of this work have been previously presented at The Challenge of Chronic Pain: From Genomics to Therapy in UK and first 1st Danish International Conference on Personalised Medicine in Denmark

Background: Chronic back pain is a complex and costly health problem, treated by a wide range of practitioners, with different belief systems and approaches. Despite the range of options available, many patients appear to be dissatisfied with the treatment that they receive. This may be due to a mismatch between patients’ and practitioners’ beliefs about the cause of the pain and their expectations for treatment. Objectives: To explore patients’ beliefs about the causes of their chronic back pain and their expectations regarding treatment. Methods: Group interviews were held with two sample groups of individuals (experiencing moderate and severe chronic pain) to inform a series of qualitative individual interviews with patients and practitioners, exploring beliefs about the causation of chronic pain and expectations for treatment. Participants were identified from respondents reporting chronic pain in a postal questionnaire survey administered through a local general practice. Participants were allocated to groups according to the severity of their pain, as measured by the Chronic Pain Grade. Those with grades II and I were allocated to group one and those with grades III and IV to group two. Results: Participants presented sophisticated accounts of their pain and their care seeking. General practitioners were seen as the most appropriate first ‘port of call’, as chronic back pain was viewed as a medical problem requiring a medical solution such as X-rays, referral to hospital specialist and eventually operations. Participants presented to their GP in hope of a medical solution, which was seldom realised. Participants appeared to be resolved to this situation, yet sustained the belief that a different way of communicating their problem to their GP may lead to appropriate action. Conclusion: There was a marked contrast between the groups on some issues, which will be explored further within this presentation

Purpose. Back pain is the primary cause of disability worldwide yet surprisingly little is known of the underlying pathobiology. We conducted a genome-wide association study (GWAS) meta-analysis of chronic back pain (CBP). Adults of European ancestry from 15 cohorts in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and UK Biobank were studied. Methods. CBP cases were defined as reporting back pain present for ≥3–6 months; non-cases were included as comparisons (“controls”). Each cohort conducted genotyping followed by imputation. GWAS used logistic regression with additive genetic effects adjusting for age, sex, study-specific covariates, and population substructure. Suggestive (p<5×10. –7. ) & genome-wide significant (p<5×10. –8. ) variants were carried forward for replication in an independent sample of UK Biobank participants. Discovery sample n = 158,025 individuals, including 29,531 CBP cases. Results. Genome-wide significant association was found for intron variant rs12310519 in SOX5 (OR=1.08, p=7.2×10. −10. ). This was replicated in the independent sample n = 283,752, comprising 50,915 cases (OR 1.06, p=5.3×10. −11. ); in joint meta-analysis OR=1.07, p=4.5×10. −19. exceeding genome-wide significance. We found three other suggestive associations in discovery, two of which exceeded genome-wide significance in joint meta-analysis: an intergenic variant rs7833174 located between CCDC26 and GSDMC (OR 1.05, p=4.4×10. −13. ), and an intron variant, rs4384683, in DCC (OR 0.97, p=2.4×10. −10. ). Conclusion. We have identified and replicated a genetic locus associated with CBP (SOX5). We also identified 2 other loci that reached genome-wide significance in a 2-stage joint meta-analysis (CCDC26/GSDMC and DCC) which will shed light on the pathogenic mechanisms underlying CBP. Conflicts of interest: YA and LK are owners of Maatschap PolyOmica. This study was supported by the European Community's Seventh Framework Programme funded project PainOmics (Grant agreement n. 602736) and conducted using the UK Biobank Resource (project # 18219). CHARGE and other cohort-specific funding sources to be submitted- see below

Aim: The evaluation of the reliability of the Oswestry disability questionnaire in postmenopausal women with osteoporosis and chronic back pain. Patients and method: 104 postmenopausal women with osteoporosis and low or upper back pain with during at least three months have been included in our study. The disability caused by the pain was estimated using Oswestry questionnaire and the pain intensity was estimated using VAS. The reported general condition of health had five interpretations: bad, not so good, satisfying, good, very good, graded by 0,1,2,3,4, respectively. Results: Statistical significant correlations was found to be between disability and pain intensity in the low back pain group (r = 0.44, P < 0.0001), pain intensity in the upper back pain (r = 0.32, P < 0.01), and the reported general condition of health (r = 0.4, P < 0.001). Conclusions: The reported statistical significant correlations increase the reliability of Oswestry questionnaire, and it can be used in the evaluation of the disability due to chronic back pain in postmenopausal women with osteoporosis

Percutaneous radiofrequency facet joint denervation (RFJD) has been used increasingly since being described by Shealy1 for the non-surgical treatment of chronic low back pain. Extensive literature exists on this technique with a number of randomised control studies suggesting efficacy against Placebo2,3. However, the efficacy and reliability of repeat RFJD for chronic back pain is unknown. A prospective study was carried out on a consecutive series of 57 patients undergoing repeat lumbar RFJD between 2004 & 2006. 57 consecutive patients treated by the senior author (OLO) between April 2004–June 2006 were included in a prospective analysis using a visual analogue score (VAS) and the low back outcome score (LBOS). All 57 participants completed a telephone questionnaire at follow up. There were no complications. At a median average follow up of 14 months overall, clinical outcomes demonstrated moderate improvement in the majority of patients with poor rating at LBOS decreasing from 54.3% pre- to 40.3% post-RFJD. The overall degree of satisfaction was 77.2%. The overall median duration of pain relief was 10 months. Our study suggests that repeat RFJD appears to have reliable and satisfactory results when repeated with most patients reporting a high degree of satisfaction and with the clinical outcome similar to the initial procedure

Cite this article: Bone Joint Res 2023;12(3):199–201.

Chronic low back pain (cLBP) is a complex, multifaceted disorder where biological, psychological, and social factors affect its onset and trajectory. Consequently, cLBP encompasses many different disease variants, with multiple patient-specific mechanisms. The goal of NIH Back Pain Consortium (BACPAC) Research Program is to develop understanding of cLBP mechanisms and to develop algorithms that optimally match specific treatments to individual patients. To accomplish this, one research activity of BACPAC is to develop theoretical models for chronic low back pain based on the current state of knowledge in the scientific community, and to interrogate the relationships implied by the theoretical models using data generated by or available to BACPAC. The models consider biopsychosocial perspectives, and encompass both peripheral (i.e. low back) and central (i.e. spinal and supra-spinal) factors as well as proposed mechanisms of action of cLBP treatments. However, absent explanations, models/algorithms may fall short of regulatory requirements and clinician expectations, and ultimately may not be embraced by physicians and patients. To address this, BACPAC is developing a clinical utility roadmap (CUR) to clarify how models will be used in practice for selecting optimal treatments, monitoring response to treatment, and reducing health care utilization. This presentation will review the goals of BACPAC and how theoretical models and CUR are being used to support computational knowledge networks to integrate data from deeply phenotyped cLBP patients.

Purpose of the study: To determine the results three to four years after a multidisciplinary programme for people with long-standing absenteeism due to chronic back pain, a longitudinal prospective cohort study was carried out. Method: A population of 143 consecutive clients who participated in 1996 in a “back to work” programme in the Rug Advies Centra, the Netherlands, was interviewed early in 2000 by telephone and using written questionnaires relating to the current work status, pain intensity, perceived disability and symptoms. The same questionnaires had been administered at the start of the programme and six months later. Differences across the three scores were tested in a multivariate design for repeated measures. The study population had taken part in earlier studies on the predictive value of the pre-intervention assessment1 and on the results relating to workstatus, pain intensity, perceived disability and symptoms after six months2. Results: The response rate was 92% (N=130). Of these, 11% did not work at all or worked a decreased number of hours per day due to back pain. At six months follow up, this figure was 13%. Of the ones who responded, 7% did not work at all at the time of interview or worked a decreased number of hours due to other symptoms. The average level of pain, disability and symptoms was lower compared to the status before entering the intervention programme (p < .001). Conclusion: The percentage of people who returned to work and stayed at work after a multidisciplinary programme remained stable over a period of three to four years. The results are good and about the same as the results after six months in terms of work status, pain intensity and symptoms

Introduction: We report a series of 90 patients enrolled in a prospective study of Dynesys stabilisation reviewed at 12 to 30 months.

The procedure involves, at each segment, cephalad and caudad pedicle screws connected with a polycarbourethane spacer and polyethylene cord. It achieves load relief and controlled flexion. Since 1996, 7000 procedures have been undertaken globally.

Method: Indications are analogous to consideration for fusion. Entry criteria included 1) Unresolved and unacceptable lumbar back pain despite protracted conservative management and 2) Definite pathology where symptoms could be abolished by anaesthetising the target segments.

Where root compression was present, a midline approach and posterior screw placement was used in conjunction with open decompression. With back pain alone a bilateral Wiltse approach and posterolateral placement was used.

All patients were assessed pre and post surgery with SF36, Oswestry Disability Index and pain analogue scores and modified Zung. Standing radiographs were obtained post surgery and at review. Follow up was at 6, 12, 24 and 52 weeks in addition to this review.

Results: Follow up was 100%. 89 patients survived. Mobilisation was achieved on day 1 and discharge usually by day 2.Based on the above outcome measures and patient satisfaction good to excellent results were achieved in 74%(66/89). Screw loosening or breakage occurred in 8%, and was associated with a poor result.

Discussion: Dynesys flexible stabilisation offers a simple alternative to fusion with less potential for adjacent ‘Domino’ failure. It differs from tension ligament systems such as Graf. At this stage the results appear at least as good as a comparable cohort of fusion patients.

The present series is early, but gives grounds for encouragement. Screw loosening and failure are technical problems detracting from the result and require further development.

We are continuing to use the technique.

INTRODUCTION: We report a series of 90 patients enrolled in a prospective study of Dynesys stabilisation reviewed at 12 to 30 months.

The procedure involves, at each segment, cephalad and caudad pedicle screws connected with a polycarbo-urethane spacer and polyethylene cord. It achieves load relief and controlled flexion. Since 1996, 7000 procedures have been undertaken globally.

METHOD: Indications are analogous to consideration for fusion. Entry criteria included (1) unresolved and unacceptable lumbar back pain despite protracted conservative management and (2) definite pathology where symptoms could be abolished by anaesthetising the target segments.

Where root compression was present, a midline approach and posterior screw placement was used in conjunction with open decompression. With back pain alone a bilateral Wiltse approach and posterolateral placement was used.

All patients were assessed pre- and post-surgery with SF36, Oswestry Disability Index and pain analogue scores and Modified Zung. Standing radiographs were obtained post- surgery and at review. Follow-up was at six, 12, 24 and 52 weeks in addition to this review.

RESULTS: Follow-up was 100%. 89 patients survived. Mobilisation was achieved on day 1 and discharge usually by day 2. Based on the above outcome measures and patient satisfaction good to excellent results were achieved in 74% (66/89). Screw loosening or breakage occurred in 8%, and was associated with a poor result.

DISCUSSION: Dynesys flexible stabilisation offers a simple alternative to fusion with less potential for adjacent ‘Domino’ failure. It differs from tension ligament systems such as Graf. At this stage the results appear at least as good as a comparable cohort of fusion patients.

The present series is early, but gives grounds for encouragement. Screw loosening and failure are technical problems detracting from the result and require further development.

We are continuing to use the technique.

Introduction of new surgical intervention need assessment of the true results by eliminating cognitive dissonance and the placebo effect. Significant time must elapse since the procedure to derive conclusions. With the initial gratifying results of Endoscopic Foraminoplasty a retrospective analysis of the data was performed to identify if the outcome was accurate and not a placebo effect.

Early postoperative Data (6 weeks and 6 months) derived from questionnaires on 91 patients with Endoscopic Foraminoplasty (April 1997 and November 1998), which included the Oswestry Disability Scale and a Visual Analogue Pain Scale was compared with the data at 2 years (late). A t-test was used to assess the difference between the Oswestry Disability scores from the two questionnaires and a Wilcoxon Signed Rank test for the Visual Analogue Pain Scale.

No significant difference between the Visual Analogue Pain Scores at 6 weeks to 6 months and 2 years post-operation was noted. There was however, a marginal improvement (p= 0.05) in Oswestry Index over two years period.

The initial outcome of Endoscopic Laser Foraminoplasty was sustained or improved at the end of two years and was not a placebo effect.

Objective: To determine the factor structure of the Coping Strategies Questionnaire (CSQ)¹ in chronic low back pain patients (CLBP) presenting for physiotherapy.

Subjects: CLBP patients presenting for their first assessment at an outpatient physiotherapy department were used (N = 105; 60% male; M age = 41 yrs; SD ± 10).

Design: A factor analysis, using varimax rotation, was performed on patients’ responses to the CSQ. Factors emerging with eigenvalues of ≥1 were considered. A coping strategy was included in a factor if it correlated with the factor at a level greater than 0.6.

Results: Three factors accounted for 70% of the variance in questionnaire responses. Factor 1, labeled Adaptive Coping, accounted for 35% of the variance and comprised the subscales for reinterpreting pain sensations, ignoring pain sensations, and coping self-statements. Factor 2, labeled Maladaptive Coping, accounted for 23% of the variance and comprised the subscales for diverting attention, catastrophizing, praying or hoping, and behavioural coping styles. The final factor, labeled Efficacy of Pain Management, accounted for 12% of the variance and comprised the two single-item scales. Adaptive Coping was positively correlated with Maladaptive Coping (r = 0.37, P < 0.01). Efficacy of Pain Management was positively correlated with Adaptive Coping (r = 0.28, P < 0.01). A non-significant negative correlation was found between Maladaptive Coping and Efficacy of Pain Management (r = −0.03, P > 0.05).

Conclusion: Three underlying factors, labelled Adaptive Coping, Maladaptive Coping, and Efficacy of Pain Management accounted for 70% of the variance in questionnaire responses.

Objectives: The view that patients low back pain presenting with ‘abnormal’ psychometric and poor DRAM scores predict an unsatisfactory surgical outcome is considered controversial. This prospective study was designed to identify if DRAM Scores (Scores of Distress Risk Assessment Method) is a predictive determinant or a reactive instrument in regard to the outcome of Endoscopic Foraminoplasty.

Design: Pre- and postoperative assessment of disability and DRAM at two years.

Subjects: One hundred and eighty-five patients (86 males and 99 females) underwent an Endoscopic Laser Foraminoplasty between April 1997 and November 1998.

Outcome measures: Oswestry Disability Scale, and the Visual Analogue Pain Scale and the DRAM scores. Patients were categorised by their pre-op DRAM score. Kruskal-Wallis analysis of variance and a regression analysis were performed.

Results: There was significant improvement in disability and pain scores at two years. (p< 0.05). A significant difference in median DRAM between the preoperative and postoperative score at two years was noted.

Conclusion: The DRAM score highlights individuals in distress who may need psychological support and physical treatment for optimum benefit from endoscopic spinal intervention. While the DRAM score predicted the patients’ disability and pain it failed to predict percentage benefit gain in outcome.

The view that patients low back pain presenting with ‘abnormal’ psychometric and poor DRAM scores predict an unsatisfactory surgical outcome is considered controversial. This prospective study was designed to identify if DRAM Scores (Scores of Distress Risk Assessment Method) is a predictive determinant or a reactive instrument in regard to the outcome of Endoscopic Foraminoplasty.

One hundred and eighty-five patients (86 males and 99 females) underwent an Endoscopic Laser Foraminoplasty between April 1997 and November 1998. Pre- and postoperative assessment at 2 years was made using the Oswestry Disability Scale, and the Visual Analogue Pain Scale and the DRAM scores. Patients were categorised by their pre-op DRAM score. A Kruskal-Wallis analysis of variance and a regression analysis were performed.

There was significant improvement in disability and pain scores at two years. (p< 0.05). A significant difference in median DRAM between the preoperative and postoperative score at two years was noted. While the DRAM score predicted the patients’ disability and pain it failed to predict the change in outcome.

The DRAM score highlights individuals in distress who may need psychological support and physical treatment for optimum benefit from endoscopic spinal intervention and not be used to deny a surgical intervention.

Tryfonidou leads the Horizon 2020 consortium (iPSpine; 2019–2023) bringing a transdisciplinary team of 21 partners together to address the challenges and bottlenecks of iPS-based advanced therapies towards their transition to the clinic. Here, chronic back pain due to intervertebral disc degeneration is employed as a show case. The project develops the iPS-technology and designed smart biomaterials to carry, protect and instruct the iPS cells within the degenerate disc environment. This work will be presented including ongoing activities focus on translating the developed methodology and tools towards clinically relevant animal models. The consortium optimized the protocol for the differentiated iPS-notochordal-like cells (iPS-NLCs) and shortlisted two biomaterials shortlisted based on their physicochemical, cytotoxicity, biomechanical and biocompatibility testing. Both were shown to be safe and have been tested with the progenitors of iPS-NLCs. An advanced platform (e.g., the dynamic loading bioreactor for disc tissue) was used to evaluate their performance: the biomaterials supported the iPS-NLC progenitors after injection into the degenerate disc and seem to also support their maturation towards NLCs. Furthermore, we confirmed the capacity of these cells to survive inside degenerated discs at 30 days upon injection in sheep, whereafter we continued with their evaluation at 3 months post-injection. We achieved full evaluation of the sheep spines, including biomechanical analysis using the portable spine biomechanics tester prior analysis at the macro- and microscopic, and biochemical level

Purpose. Cognitive Muscular Therapy (CMT) is a new treatment for low back pain which integrates psychological techniques for pain management alongside training to improve postural control. Rather than focus on postural alignment or strength, CMT aims to improve the regulation of postural tone (low-level activity which supports the body against gravity). This is achieved by teaching patients an awareness of compensatory paraspinal activation, which can be triggered by overactivity of the abdominal muscles. The aim of this study was to understand whether CMT could reduce symptoms associated with low back pain and improve paraspinal muscle activation. Methods and results. Fifteen patients with chronic low back pain received seven weekly sessions of CMT from a physiotherapist. Clinical data was captured at baseline and two weeks after the intervention using the Roland-Morris questionnaire and the pain catastrophising scale. Activation of the erector spinae muscle during walking was also measured at baseline and after the final intervention session. Change data were analysed using paired t-tests. There was a 75% reduction (p<0.001) in the Roland-Morris score from a mean (SD) of 9.3(2.9) to 2.3(2.6), along with a 78% reduction in pain catastrophising (p<0.002) from 16.6(13) to 3.7(4.8). Activation of the contralateral erector spinae muscles reduced by 30% (p<0.01) during the contralateral swing phase of walking. Conclusion. In this small sample, CMT delivered large clinical improvements and reduced activation of the low back muscles during walking. Larger randomised trials are now required to confirm whether CMT could outperform existing physiotherapy treatments for chronic back pain. Conflict of interest. No conflicts of interest. Source of funding. University of Salford

Intervertebral disc (IVD) degeneration is responsible for severe clinical symptoms including chronic back pain. Galectins are a family of carbohydrate-binding proteins, some of which can induce functional disease markers in IVD cells and other musculoskeletal diseases. Galectins −4 and −8 were shown to trigger disease-promoting activity in chondrocytes but their effects on IVD cells have not been investigated yet. This study elucidates the role of galectin-4 and −8 in IVD degeneration. Immunohistochemical evidence for the presence of galectin-4 and −8 in the IVD was comparatively provided in specimens of 36 patients with spondylochondrosis, spondylolisthesis, or spinal deformity. Confocal microscopy revealed co-localization of galectin-4 and −8 in chondrocyte clusters of degenerated cartilage. The immunohistochemical presence of galectin-4 correlated with histopathological and clinical degeneration scores of patients, whereas galectin-8 did not show significant correlations. The specimens were separated into annulus fibrosus (AF), nucleus pulposus (NP) and endplate, which was confirmed histologically. Separate cell cultures of AF and NP (n=20) were established and characterized using cell type-specific markers. Potential binding sites for galectins including sialylated N-glycans and LacdiNAc structures were determined in AF and NP cells using LC/ESI-MS-MS. To assess galectin functions, cell cultures were treated with recombinant galectin-4 or −8, in comparison to IL-1β, and analyzed using RT-qPCR and In-cell Western blot. In vitro, both galectins triggered the induction of functional disease markers (CXCL8 and MMP3) on mRNA level and activated the nuclear factor-kB pathway. NP cells were significantly more responsive to galectin-8 and Il-1β than AF cells. Phosphorylation of p-65 was time-dependently induced by both galectins in both cell types to a comparable extent. Taken together, this study provides evidence for a functional role of glycobiological processes in IVD degeneration and highlights galectin-4 and −8 as regulators of pro-inflammatory and degrative processes in AF and NP cells

Background. Lateral lumbar spine statistical shape models (SSM) have been used previously to describe associations with osteoarthritis and back pain. However, associations with factors such as osteoporosis, menopause and parity have not been explored. Methods and Results. A 143-point SSM, describing L1 to the top of L5, was applied to lateral spine iDXA scans from UK Biobank. Associations with self-reported osteoporosis, menopause, parity and back pain and the first 10 modes of variation were examined using adjusted binary logistic regression or linear regression (adjusted for age, height, weight and total spine BMD). We report odds ratios with 95% confidence intervals for each standard deviation change in mode. Complete data were available for 2494 women. Mean age was 61.5 (± 7.4) years. 1369 women reported going through menopause, 96 women self-reported osteoporosis and 339 women reported chronic back pain. 80% of women reported at least 1 live birth. Lumbar spine shape was not associated with back pain in this cohort. Two modes were associated with menopause (modes 1 & 2), 1 mode with parity (mode 1) and 2 modes with osteoporosis (modes 3 & 5). Mode 1 (43.6% total variation), describing lumbar curvature was positively associated with both menopause [OR 1.15 95% CI 1.00–1.33, p=0.05] and parity [OR 1.058 95% CI 1.03–1.0, p=0.01]. Mode 3, describing decreased vertebral height was positively associated with osteoporosis [OR 1.40 95% CI 1.14–1.73, p=0.001]. Conclusion. Menopause and parity were associated with a curvier lumbar spine and osteoporosis with decreased vertebral height. Shape was not associated with back pain. No conflicts of interest.  . Sources of funding. Wellcome Trust collaborative award ref 209233

Intervertebral disc (IVD) degeneration is a pathological process often associated with chronic back pain and considered a leading cause of disability worldwide. 1. During degeneration, progressive structural and biochemical changes occur, leading to blood vessel and nerve ingrowth and promoting discogenic pain. 2. In the last decades, several cytokines have been applied to IVD cells in vitro to investigate the degenerative cascade. Particularly, IL-10 and IL-4 have been predicted as important anabolic factors in the IVD according to a regulatory network model based in silico approach. 3. Thus, we aim to investigate the potential presence and anabolic effect of IL-10 and IL-4 in human NP cells (in vitro) and explants (ex vivo) under hypoxia (5% O2) after a catabolic induction. Primary human NP cells were expanded, encapsulated in 1.2% alginate beads (4 × 106 cells/ml) and cultured for two weeks in 3D for phenotype recovery while human NP explants were cultured for five days. Afterwards, both alginate and explant cultures were i) cultured for two days and subsequently treated with 10 ng/ml IL-10 or IL-4 (single treatments) or ii) stimulated with 0.1 ng/ml IL-1β for two days and subsequently treated with 10 ng/ml IL-10 or IL-4 (combined treatments). The presence of IL-4 receptor, IL-4 and IL-10 was confirmed in human intact NP tissue (Fig 1). Additionally, IL-4 single and combined treatments induced a significant increase of proinflammatory protein secretion in vitro (Fig. 2A-C) and ex vivo (Fig. 2D and E). In contrast, no significant differences were observed in the secretome between IL-10 single and combined treatments compared to control group. Overall, IL-4 containing treatments promote human NP cell and explant catabolism in contrast to previously reported IL-4 anti-inflammatory performance. 4. Thus, a possible pleiotropic effect of IL-4 could occur depending on the IVD culture and environmental condition. Acknowledgements: This project was supported by the Marie Skłodowska Curie International Training Network “disc4all” under the grant agreement #955735. For any figures and tables, please contact the authors directly