Aims. CRP is an acute-phase protein that is used as a biomarker to follow severity and progression in infectious and inflammatory diseases. Its pathophysiological mechanisms of action are still poorly defined. CRP in its pentameric form exhibits weak anti-inflammatory activity. The monomeric isoform (mCRP) exerts potent proinflammatory properties in chondrocytes, endothelial cells, and leucocytes. No data exist regarding mCRP effects in human intervertebral disc (IVD) cells. This work aimed to verify the pathophysiological relevance of mCRP in the aetiology and/or progression of IVD degeneration. Methods. We investigated the effects of mCRP and the signalling pathways that are involved in cultured human primary annulus fibrosus (AF) cells and in the human nucleus pulposus (NP) immortalized cell line HNPSV-1. We determined messenger RNA (mRNA) and protein levels of relevant factors involved in inflammatory responses, by quantitative real-time polymerase chain reaction (RT-qPCR) and western blot. We also studied the presence of mCRP in human AF and NP tissues by immunohistochemistry. Results. We demonstrated that mCRP increases nitric oxide synthase 2 (NOS2), cyclooxygenase 2 (COX2), matrix metalloproteinase 13 (MMP13), vascular cell adhesion molecule 1 (VCAM1), interleukin (IL)-6, IL-8, and Lipocalin 2 (LCN2) expression in human AF and NP cells. We also showed that nuclear factor-κβ (NF-κβ), extracellular signal-regulated kinase 1/2 (ERK1/2), and phosphoinositide 3-kinase (PI3K) are at play in the intracellular signalling of mCRP. Finally, we demonstrated the presence of mCRP in human AF and NP tissues. Conclusion. Our results indicate, for the first time, that mCRP can be localized in IVD tissues, where it triggers a proinflammatory and catabolic state in degenerative and healthy IVD cells, and that NF-κβ signalling may be implicated in the mediation of this mCRP-induced state. Cite this article: Bone Joint Res 2023;12(3):189–198

Discogenic low back pain is a common cause of disability, but its pathogenesis is poorly understood. We collected 19 specimens of lumbar intervertebral discs from 17 patients with discogenic low back pain during posterior lumbar interbody fusion, 12 from physiologically ageing discs and ten from normal control discs. We investigated the histological features and assessed the immunoreactive activity of neurofilament (NF200) and neuropeptides such as substance P (SP) and vasoactive-intestinal peptide (VIP) in the nerve fibres. The distinct histological characteristic of the painful disc was the formation of a zone of vascularised granulation tissue from the nucleus pulposus to the outer part of the annulus fibrosus along the edges of the fissures. SP-, NF- and VIP-immunoreactive nerve fibres in the painful discs were more extensive than in the control discs. Growth of nerves deep into the annulus fibrosus and nucleus pulposus was observed mainly along the zone of granulation tissue in the painful discs. This suggests that the zone of granulation tissue with extensive innervation along the tears in the posterior part of the painful disc may be responsible for causing the pain of discography and of discogenic low back pain

Aims

In this investigation, we administered oxidative stress to nucleus pulposus cells (NPCs), recognized DNA-damage-inducible transcript 4 (DDIT4) as a component in intervertebral disc degeneration (IVDD), and devised a hydrogel capable of conveying small interfering RNA (siRNA) to IVDD.

Aims

This study aimed, through bioinformatics analysis and in vitro experiment validation, to identify the key extracellular proteins of intervertebral disc degeneration (IDD).

Aims

This study was performed to explore the effect of melatonin on pyroptosis in nucleus pulposus cells (NPCs) and the underlying mechanism of that effect.

Aims

The aim of the study was to determine if there was a direct correlation between the pain and disability experienced by patients and size of their disc prolapse, measured by the disc’s cross-sectional area on T2 axial MRI scans.

Aims

To study the associations of lumbar developmental spinal stenosis (DSS) with low back pain (LBP), radicular leg pain, and disability.

Aims

The aim of this study was to determine the differences in spinal imaging characteristics between subjects with or without lumbar developmental spinal stenosis (DSS) in a population-based cohort.

Objectives

Many studies have investigated the kinematics of the lumbar spine and the morphological features of the lumbar discs. However, the segment-dependent immediate changes of the lumbar intervertebral space height during flexion-extension motion are still unclear. This study examined the changes of intervertebral space height during flexion-extension motion of lumbar specimens.

The belief that an intervertebral disc must degenerate before it can herniate has clinical and medicolegal significance, but lacks scientific validity. We hypothesised that tissue changes in herniated discs differ from those in discs that degenerate without herniation. Tissues were obtained at surgery from 21 herniated discs and 11 non-herniated discs of similar degeneration as assessed by the Pfirrmann grade. Thin sections were graded histologically, and certain features were quantified using immunofluorescence combined with confocal microscopy and image analysis. Herniated and degenerated tissues were compared separately for each tissue type: nucleus, inner annulus and outer annulus.

Herniated tissues showed significantly greater proteoglycan loss (outer annulus), neovascularisation (annulus), innervation (annulus), cellularity/inflammation (annulus) and expression of matrix-degrading enzymes (inner annulus) than degenerated discs. No significant differences were seen in the nucleus tissue from herniated and degenerated discs. Degenerative changes start in the nucleus, so it seems unlikely that advanced degeneration caused herniation in 21 of these 32 discs. On the contrary, specific changes in the annulus can be interpreted as the consequences of herniation, when disruption allows local swelling, proteoglycan loss, and the ingrowth of blood vessels, nerves and inflammatory cells.

In conclusion, it should not be assumed that degenerative changes always precede disc herniation.

Cite this article: Bone Joint J 2013;95-B:1127–33.

This article reviews the current knowledge of the intervertebral disc (IVD) and its association with low back pain (LBP). The normal IVD is a largely avascular and aneural structure with a high water content, its nutrients mainly diffusing through the end plates. IVD degeneration occurs when its cells die or become dysfunctional, notably in an acidic environment. In the process of degeneration, the IVD becomes dehydrated and vascularised, and there is an ingrowth of nerves. Although not universally the case, the altered physiology of the IVD is believed to precede or be associated with many clinical symptoms or conditions including low back and/or lower limb pain, paraesthesia, spinal stenosis and disc herniation.

New treatment options have been developed in recent years. These include biological therapies and novel surgical techniques (such as total disc replacement), although many of these are still in their experimental phase. Central to developing further methods of treatment is the need for effective ways in which to assess patients and measure their outcomes. However, significant difficulties remain and it is therefore an appropriate time to be further investigating the scientific basis of and treatment of LBP.

This short contribution aims to explain how intervertebral disc ‘degeneration’ differs from normal ageing, and to suggest how mechanical loading and constitutional factors interact to cause disc degeneration and prolapse. We suggest that disagreement on these matters in medico-legal practice often arises from a misunderstanding of the nature of ‘soft-tissue injuries’.

A number of causes have been advanced to explain the destructive discovertebral (Andersson) lesions that occur in ankylosing spondylitis, and various treatments have been proposed, depending on the presumed cause. The purpose of this study was to identify the causes of these lesions by defining their clinical and radiological characteristics.

We retrospectively reviewed 622 patients with ankylosing spondylitis. In all, 33 patients (5.3%) had these lesions, affecting 100 spinal segments. Inflammatory lesions were found in 91 segments of 24 patients (3.9%) and traumatic lesions in nine segments of nine patients (1.4%). The inflammatory lesions were associated with recent-onset disease; a low modified Stoke ankylosing spondylitis spine score (mSASSS) due to incomplete bony ankylosis between vertebral bodies; multiple lesions; inflammatory changes on MRI; reversal of the inflammatory changes and central bony ankylosis at follow-up; and a good response to anti-inflammatory drugs. Traumatic lesions were associated with prolonged disease duration; a high mSASSS due to complete bony ankylosis between vertebral bodies; a previous history of trauma; single lesions; nonunion of fractures of the posterior column; acute kyphoscoliotic deformity with the lesion at the apex; instability, and the need for operative treatment due to that instability.

It is essential to distinguish between inflammatory and traumatic Andersson lesions, as the former respond to medical treatment whereas the latter require surgery.

No previous studies have examined the physical characteristics of patients with cauda equina syndrome (CES). We compared the anthropometric features of patients who developed CES after a disc prolapse with those who did not but who had symptoms that required elective surgery. We recorded the age, gender, height, weight and body mass index (BMI) of 92 consecutive patients who underwent elective lumbar discectomy and 40 consecutive patients who underwent discectomy for CES. On univariate analysis, the mean BMI of the elective discectomy cohort (26.5 kg/m² (16.6 to 41.7) was very similar to that of the age-matched national mean (27.6 kg/m², p = 1.0). However, the mean BMI of the CES cohort (31.1 kg/m² (21.0 to 54.9)) was significantly higher than both that of the elective group (p < 0.001) and the age-matched national mean (p < 0.001). A similar pattern was seen with the weight of the groups. Multivariate logistic regression analysis was performed, adjusted for age, gender, height, weight and BMI. Increasing BMI and weight were strongly associated with an increased risk of CES (odds ratio (OR) 1.17, p < 0.001; and OR 1.06, p <  0.001, respectively). However, increasing height was linked with a reduced risk of CES (OR 0.9, p < 0.01). The odds of developing CES were 3.7 times higher (95% confidence interval (CI) 1.2 to 7.8, p = 0.016) in the overweight and obese (as defined by the World Health Organization: BMI ≥ 25 kg/m²) than in those of ideal weight. Those with very large discs (obstructing > 75% of the spinal canal) had a larger BMI than those with small discs (obstructing < 25% of the canal; p < 0.01). We therefore conclude that increasing BMI is associated with CES.

We studied 52 patients, each with a lumbosacral transitional vertebra. Using MRI we found that the lumbar discs immediately above the transitional vertebra were significantly more degenerative and those between the transitional vertebrae and the sacrum were significantly less degenerative compared with discs at other levels. We also performed an anatomical study using 70 cadavers. We found that the iliolumbar ligament at the level immediately above the transitional vertebra was thinner and weaker than it was in cadavers without a lumbosacral transitional vertebra.

Instability of the vertebral segment above the transitional vertebra because of a weak iliolumbar ligament could lead to subsequent disc degeneration which may occur earlier than at other disc levels. Some stability between the transitional vertebra and the sacrum could be preserved by the formation of either an articulation or by bony union between the vertebra and the sacrum through its transverse process. This may protect the disc from further degeneration in the long term.