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Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_I | Pages 28 - 28
1 Jan 2012
Stefanakis M Luo J Harding I Dolan P Adams M
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Background. Fissures in the anulus fibrosus are common in disc degeneration, and are associated with discogenic pain. We hypothesise that anulus fissures are conducive to the ingrowth of blood vessels and nerves. Purpose. To investigate the mechanical and chemical micro-environment of anulus fissures. Methods. Six thoracolumbar spine specimens, comprising three vertebrae and two discs, were obtained from cadavers aged 68-83 yr. Discs were injected with blue dye to reveal the location of complete anulus fissures. Each specimen was then subjected to 1000 N compression, while intradiscal compressive stress was investigated by pulling a miniature pressure transducer through the disc, in planes likely to cross the anulus fissures. Some additional disc fragments were removed at surgery from patients with discogenic back pain, and examined histologically to gauge the concentration of collagen and proteoglycans within radial fissures, using a qualitative method. Results. Stress profiles were obtained perpendicular to major anulus fissures in seven discs. A marked local reduction in vertically-acting compressive stress usually coincided with fissure location (confirmed at dissection), and stress reductions were inversely proportional to average pressure in the nucleus (r. 2. =0.56, p<0.05). Surgical disc samples showed local depletion of proteoglycans around the margins of radial and circumferential fissures, leaving a collagen-rich scaffold of the type known to support nerve and blood vessel growth. Conclusion. Compressive stresses within anulus fissures are reduced most when the disc nucleus is decompressed, because this facilitates internal displacements of disrupted tissue. Anulus fissures provide a micro-environment that is mechanically and chemically conducive to the ingrowth of blood vessels and nerves


The Bone & Joint Journal
Vol. 98-B, Issue 3 | Pages 387 - 394
1 Mar 2016
Eguchi Y Oikawa Y Suzuki M Orita S Yamauchi K Suzuki M Aoki Y Watanabe A Takahashi K Ohtori S

Aims. The aim of this study was to evaluate the time course of changes in parameters of diffusion tensor imaging (DTI) such as fractional anisotropy (FA) and apparent diffusion coefficient (ADC) in patients with symptomatic lumbar disc herniation. We also investigated the correlation between the severity of neurological symptoms and these parameters. . Patients and Methods. A total of 13 patients with unilateral radiculopathy due to herniation of a lumbar disc were investigated with DTI on a 1.5T MR scanner and underwent micro discectomy. There were nine men and four women, with a median age of 55.5 years (19 to 79). The changes in the mean FA and ADC values and the correlation between these changes and the severity of the neurological symptoms were investigated before and at six months after surgery. . Results. The mean FA values were significantly lower (p = 0.0005) and mean ADC values were significantly higher (p = 0.0115) in compressed nerves than in intact nerves. Although the FA values increased significantly at six months after surgical treatment (p = 0.020), the ADC values decreased but not significantly (p = 0.498). There were strong correlations between the DTI parameters such as the FA value and the severity of the neurological symptoms as assessed using the Japanese Orthopaedic Association (JOA) score and the Roland-Morris Disability Questionnaire (RDQ). . Conclusion. This preliminary study suggests that it may be possible to use DTI to diagnose, quantitatively evaluate and follow-up patients with lumbar nerve entrapment. Take home message: DTI is a potential tool for functional diagnosis of lumbar nerve damage. Cite this article: Bone Joint J 2016;98-B:387–94


Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_10 | Pages 36 - 36
1 Oct 2019
Partridge S Maitre C Sammon C
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Introduction. Musculoskeletal diseases are the biggest cause of morbidity worldwide, with low back pain (LBP) being the leading cause. Forty percent of LBP cases are caused by disease of shock absorbers in the spine known as intervertebral discs (IVDs). The IVDs enable the spine to twist and bend, whilst absorbing load during normal daily activities. The durability of this tissue is sustained by the cells of the spine and so during disease or mechanical damage these cells can behave abnormally further damaging the disc and stimulating local nerves causing extreme pain. Degradation of the intervertebral disc (IVD) currently has no preventative treatment; an injectable hydrogel biomaterial could reinforce disc mechanical properties and promote tissue regeneration. Methods and Results. We present an injectable range of hydrogel biomaterials made from water, clay and polymer that set at 37°C. The materials were made at 80°C polymerised in water and stored at 70°C to remain liquid. The physical properties of the materials were assessed using various methods, including mechanical assessment using temperature-controlled rheometry to monitor the liquid-hydrogel transition. Conclusion. Results showed that by changing three factors within the formulation we can produce a range of materials with suitable mechanical and morphological properties for a variety of tissues of the spine. These types of biomaterials have the potential to provide the first efficacious early-mid stage treatment for IVD disease and reduce the cost of LBP on our health services. Conflicts of interest: CS and CLM are named inventors on the patent for NPgel/BGel. Funded by the Medical Research Council and Versus Arthritis UK: SNiPER


The Journal of Bone & Joint Surgery British Volume
Vol. 78-B, Issue 5 | Pages 754 - 758
1 Sep 1996
Ochiai N Nagano A Sugioka H Hara T

We have assessed the efficacy of free nerve grafts in 90 cases of brachial plexus injury. Relatively good recovery of the elbow flexor and extensor muscles and of those of the shoulder girdle was found but recovery of the flexors and extensors of the forearm and of the intrinsic muscles of the hand was extremely poor. Poor results were found when spinal nerve roots seemed normal to the touch and appeared intact but had abnormal somatosensory evoked potentials or myelography. Recovery of the deltoid and infraspinatus muscles was better when injury had occurred to the circumflex and suprascapular nerves rather than to the plexus itself, perhaps because these nerves were explored in their entirety to determine the presence of multiple lesions. It is important to visualise the entire nerve thoroughly to assess the overall condition. Thorough exploration of the plexus and the use of intraoperative recording of somatosensory evoked potentials are essential


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 10 | Pages 1298 - 1304
1 Oct 2012
Hughes SPF Freemont AJ Hukins DWL McGregor AH Roberts S

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


Bone & Joint Research
Vol. 1, Issue 9 | Pages 198 - 204
1 Sep 2012
Iwase T Takebayashi T Tanimoto K Terashima Y Miyakawa T Kobayashi T Tohse N Yamashita T

Objectives. In order to elucidate the influence of sympathetic nerves on lumbar radiculopathy, we investigated whether sympathectomy attenuated pain behaviour and altered the electrical properties of the dorsal root ganglion (DRG) neurons in a rat model of lumbar root constriction. Methods. Sprague-Dawley rats were divided into three experimental groups. In the root constriction group, the left L5 spinal nerve root was ligated proximal to the DRG as a lumbar radiculopathy model. In the root constriction + sympathectomy group, sympathectomy was performed after the root constriction procedure. In the control group, no procedures were performed. In order to evaluate the pain relief effect of sympathectomy, behavioural analysis using mechanical and thermal stimulation was performed. In order to evaluate the excitability of the DRG neurons, we recorded action potentials of the isolated single DRG neuron by the whole-cell patch-clamp method. Results. In behavioural analysis, sympathectomy attenuated the mechanical allodynia and thermal hyperalgesia caused by lumbar root constriction. In electrophysiological analysis, single isolated DRG neurons with root constriction exhibited lower threshold current, more depolarised resting membrane potential, prolonged action potential duration, and more depolarisation frequency. These hyperexcitable alterations caused by root constriction were significantly attenuated in rats treated with surgical sympathectomy. Conclusion. The present results suggest that sympathectomy attenuates lumbar radicular pain resulting from root constriction by altering the electrical property of the DRG neuron itself. Thus, the sympathetic nervous system was closely associated with lumbar radicular pain, and suppressing the activity of the sympathetic nervous system may therefore lead to pain relief


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_4 | Pages 45 - 45
1 Feb 2014
Al-Kaisy A Pang D
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Introduction. Percutaneous radiofrequency lesioning of the lateral branches of the sacroiliac joint has become a recognised method of treating chronic pain arising from this joint. Due to the large and varied innervation from the S1-3 lateral branches success has been achieved with large lesions that has a high chance of covering these nerves. Such lesions require specialised and expensive equipment and the NIMBUS needle is a large 17G electrode with expandable tines at the tip. It is compatible with all standard radiofrequency probes and it produces a large lesion at the tip. It has been in use in the USA in over 100 cases and we describe its use in the UK. Methods. Patients were identified as having sacroiliac joint pain by clinical assessment and positive pain response to local anaesthetic sacroiliac joint lateral branch blocks. Under fluoroscopic control, the needle is inserted at the lateral edge of the sacral S1-3 posterior foramen. Three lesions at the lateral edge of the foramen are made at 80°C for 90s. A further lesion is made at the L5 dorsal ramus. Results. 4 patients achieved very good pain relief >50% reduction in pain scores on the NRS scale at 6 weeks follow up. No complications were noted and there were no technical difficulties. Conclusion. Lesioning with the NIMBUS needle is feasible and allows clinicians a method of treating chronic sacroiliac joint pain using existing radiofrequency equipment. Further large, long term studies are warranted to establish clinical efficacy


The Bone & Joint Journal
Vol. 103-B, Issue 8 | Pages 1392 - 1399
2 Aug 2021
Kang TW Park SY Oh H Lee SH Park JH Suh SW

Aims

Open discectomy (OD) is the standard operation for lumbar disc herniation (LDH). Percutaneous endoscopic lumbar discectomy (PELD), however, has shown similar outcomes to OD and there is increasing interest in this procedure. However despite improved surgical techniques and instrumentation, reoperation and infection rates continue and are reported to be between 6% and 24% and 0.7% and 16%, respectively. The objective of this study was to compare the rate of reoperation and infection within six months of patients being treated for LDH either by OD or PELD.

Methods

In this retrospective, nationwide cohort study, the Korean National Health Insurance database from 1 January 2007 to 31 December 2018 was reviewed. Data were extracted for patients who underwent OD or PELD for LDH without a history of having undergone either procedure during the preceding year. Individual patients were followed for six months through their encrypted unique resident registration number. The primary endpoints were rates of reoperation and infection during the follow-up period. Other risk factors for reoperation and infection were also evalulated.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_X | Pages 89 - 89
1 Apr 2012
Nath C Chen Y Wilder-Smith E Kumar N
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Magnetic Resonance Imaging (MRI) is the cornerstone investigation for cervical disc disease (CDD). However, MRI changes suggestive of CDD are found in people above forty, even in asymptomatic healthy individuals [1]. Mere presence of MRI changes of CDD does not exclude the presence of concomitant extra-foraminal pathology. No study design. We present here a series of three cases where use of ‘high resolution ultrasound’ has allowed accurate diagnosis of concomitant extra-foraminal pathology in patients with MRI-proven CDD. The three cases were acute neuropraxia of aberrant C5 nerve root, anterior interossous nerve compression due to pseudo-aneurysm of brachial artery and ‘acute brachial neuritis’ respectively. No outcome measure. Use of diagnostic high resolution ultrasound revealed accurate diagnosis of concomitant extra-foraminal pathology in all three cases. The cases with acute neuropraxia and acute brachial neuritis recovered with conservative treatment. Pseudo-aneurysm was treated successfully with surgery. High resolution ultrasound of the brachial plexus and peripheral nerves may be useful in following scenarios to identify an extra-foraminal pathology: (1) when symptoms and signs are out of proportion to the MRI findings of CDD; (2) when there is obvious discordance between MRI and nerve conduction findings; (3) where an entrapment neuropathy is suspected but the site of nerve lesion cannot be located


The Journal of Bone & Joint Surgery British Volume
Vol. 83-B, Issue 3 | Pages 328 - 331
1 Apr 2001
Naique S Laheri VJ

Craniodiaphyseal dysplasia (CDD) is a rare sclerosing bone disorder, the severity of which depends on its phenotypic expression. Hyperostosis can cause progressive foraminal stenosis leading to palsy of cranial nerves, epilepsy and mental retardation. We report the only case of CDD in an adult, with stenosis of the cervical canal leading to quadriparesis as a late complication of hyperostosis, and describe the problems associated with its treatment. Although the syndrome is rare, its pathophysiological and therapeutic considerations may be applicable to the management of stenosis of the spinal canal in other hyperostotic bone disorders


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXVII | Pages 8 - 8
1 Jun 2012
Repko M Horky D Chaloupka R Lauschova I
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Introduction. Autonomic nerve system (ANS) regulates intercostal vascular nutrition (internal mammary artery), and its pathological status leads to developmental asymmetry of the trunk and rib cage, and consequently producing scoliotic deformity of the spine. The aim of this study is to investigate the possible causation of idiopathic scoliosis in development abnormalities of ANS. Methods. We evaluated samples taken from 12 patients with idiopathic scoliotic deformities and a control set of three patients without scoliotic deformity. We examined the samples of autonomic nerves taken from convexity and concavity of the scoliotic deformity during the patients' surgical correction by the transthoracic approach. We used the electronmicroscopic method to analyse samples, and the morphometric method for statistical evaluation. Results. Evaluation of the samples taken from scoliotic convexity and the control samples of non-scoliotic patients showed normal findings in autonomic nerve structures. We detected significant morphological changes in all scoliotic samples taken from concavity. These changes were mostly in myelin vaginas with abnormalities and compression of the axon fibre, massive lesion and separation of the myelin sheath, vacualisation of cytoplasma of the Schwann cells, and condensation of the cytoblast. By morphometric measurements we found 23·71% of myelinised nerve fibres (MNF), 12·21% of unmyelinised nerve fibres (UNF), and 5·0% of Schwann cells (SC) in samples taken from scoliotic convexity, and 29·9% of MNF, 19·9% of UNF, and 16·7% of SC in control non-scoliotic samples. We recorded 17·36% of MNF, 5·82% of UNF, and 5·27% of SC in samples taken from concavity. Conclusions. We noted abnormalities in structure of ANS in concave side of scoliotic curves, and statistically significant differences between both sides of scoliotic deformity (convexity and concavity). Furthermore, we recorded discrepancies between scoliotic samples and non-scoliotic control samples. The abnormalities, mostly in the myelinated fibres, might be originated by the primary genetic lesion and thus could affect the development of scoliosis. The abnormalities of ANS can produce changes in internal mammary artery, and consequently can lead to the abnormal blood supply of vertebrae as well as anterior wall chest. These abnormalities of ANS could lead to the scoliotic origin in growing spine


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 1 | Pages 62 - 67
1 Jan 2005
Peng B Wu W Hou S Li P Zhang C Yang Y

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


The Journal of Bone & Joint Surgery British Volume
Vol. 78-B, Issue 4 | Pages 606 - 612
1 Jul 1996
Nakamura S Takahashi K Takahashi Y Yamagata M Moriya H

The afferent pathways of discogenic low-back pain have not been fully investigated. We hypothesised that this pain was transmitted mainly by sympathetic afferent fibres in the L2 nerve root, and in 33 patients we used selective local anaesthesia of this nerve. Low-back pain disappeared or significantly decreased in all patients after the injection. Needle insertion provoked pain which radiated to the low back in 23 patients and the area of skin hypoalgesia produced included the area of pre-existing pain in all but one. None of the nine patients with related sciatica had relief of that component of their symptoms. Our findings show that the main afferent pathways of pain from the lower intervertebral discs are through the L2 spinal nerve root, presumably via sympathetic afferents from the sinuvertebral nerves. Discogenic low-back pain should be regarded as a visceral pain in respect of its neural pathways. Infiltration of the L2 nerve is a useful diagnostic test and also has some therapeutic value


The Bone & Joint Journal
Vol. 102-B, Issue 8 | Pages 1062 - 1071
1 Aug 2020
Cheung JPY Fong HK Cheung PWH

Aims

To determine the effectiveness of prone traction radiographs in predicting postoperative slip distance, slip angle, changes in disc height, and lordosis after surgery for degenerative spondylolisthesis of the lumbar spine.

Methods

A total of 63 consecutive patients with a degenerative spondylolisthesis and preoperative prone traction radiographs obtained since 2010 were studied. Slip distance, slip angle, disc height, segmental lordosis, and global lordosis (L1 to S1) were measured on preoperative lateral standing radiographs, flexion-extension lateral radiographs, prone traction lateral radiographs, and postoperative lateral standing radiographs. Patients were divided into two groups: posterolateral fusion or posterolateral fusion with interbody fusion.


The Bone & Joint Journal
Vol. 102-B, Issue 6 | Pages 677 - 682
1 Jun 2020
Katzouraki G Zubairi AJ Hershkovich O Grevitt MP

Aims

Diagnosis of cauda equina syndrome (CES) remains difficult; clinical assessment has low accuracy in reliably predicting MRI compression of the cauda equina (CE). This prospective study tests the usefulness of ultrasound bladder scans as an adjunct for diagnosing CES.

Methods

A total of 260 patients with suspected CES were referred to a tertiary spinal unit over a 16-month period. All were assessed by Board-eligible spinal surgeons and had transabdominal ultrasound bladder scans for pre- and post-voiding residual (PVR) volume measurements before lumbosacral MRI.


The Bone & Joint Journal
Vol. 100-B, Issue 1 | Pages 81 - 87
1 Jan 2018
Peng B Yang L Yang C Pang X Chen X Wu Y

Aims

Cervical spondylosis is often accompanied by dizziness. It has recently been shown that the ingrowth of Ruffini corpuscles into diseased cervical discs may be related to cervicogenic dizziness. In order to evaluate whether cervicogenic dizziness stems from the diseased cervical disc, we performed a prospective cohort study to assess the effectiveness of anterior cervical discectomy and fusion on the relief of dizziness.

Patients and Methods

Of 145 patients with cervical spondylosis and dizziness, 116 underwent anterior cervical decompression and fusion and 29 underwent conservative treatment. All were followed up for one year. The primary outcomes were measures of the intensity and frequency of dizziness. Secondary outcomes were changes in the modified Japanese Orthopaedic Association (mJOA) score and a visual analogue scale score for neck pain.


The Bone & Joint Journal
Vol. 97-B, Issue 12 | Pages 1683 - 1692
1 Dec 2015
Patel A James SL Davies AM Botchu R

The widespread use of MRI has revolutionised the diagnostic process for spinal disorders. A typical protocol for spinal MRI includes T1 and T2 weighted sequences in both axial and sagittal planes. While such an imaging protocol is appropriate to detect pathological processes in the vast majority of patients, a number of additional sequences and advanced techniques are emerging. The purpose of the article is to discuss both established techniques that are gaining popularity in the field of spinal imaging and to introduce some of the more novel ‘advanced’ MRI sequences with examples to highlight their potential uses.

Cite this article: Bone Joint J 2015;97-B:1683–92.


The Bone & Joint Journal
Vol. 100-B, Issue 4 | Pages 499 - 506
1 Apr 2018
Minamide A Yoshida M Simpson AK Nakagawa Y Iwasaki H Tsutsui S Takami M Hashizume H Yukawa Y Yamada H

Aims

The aim of this study was to investigate the clinical and radiographic outcomes of microendoscopic laminotomy in patients with lumbar stenosis and concurrent degenerative spondylolisthesis (DS), and to determine the effect of this procedure on spinal stability.

Patients and Methods

A total of 304 consecutive patients with single-level lumbar DS with concomitant stenosis underwent microendoscopic laminotomy without fusion between January 2004 and December 2010. Patients were divided into two groups, those with and without advanced DS based on the degree of spondylolisthesis and dynamic instability. A total of 242 patients met the inclusion criteria. There were 101 men and 141 women. Their mean age was 68.1 years (46 to 85). Outcome was assessed using the Japanese Orthopaedic Association and Roland Morris Disability Questionnaire scores, a visual analogue score for pain and the Short Form Health-36 score. The radiographic outcome was assessed by measuring the slip and the disc height. The clinical and radiographic parameters were evaluated at a mean follow-up of 4.6 years (3 to 7.5).


The Bone & Joint Journal
Vol. 97-B, Issue 3 | Pages 358 - 365
1 Mar 2015
Zhu L F. Zhang Yang D Chen A

The aim of this study was to evaluate the feasibility of using the intact S1 nerve root as a donor nerve to repair an avulsion of the contralateral lumbosacral plexus. Two cohorts of patients were recruited. In cohort 1, the L4–S4 nerve roots of 15 patients with a unilateral fracture of the sacrum and sacral nerve injury were stimulated during surgery to establish the precise functional distribution of the S1 nerve root and its proportional contribution to individual muscles. In cohort 2, the contralateral uninjured S1 nerve root of six patients with a unilateral lumbosacral plexus avulsion was transected extradurally and used with a 25 cm segment of the common peroneal nerve from the injured leg to reconstruct the avulsed plexus.

The results from cohort 1 showed that the innervation of S1 in each muscle can be compensated for by L4, L5, S2 and S3. Numbness in the toes and a reduction in strength were found after surgery in cohort 2, but these symptoms gradually disappeared and strength recovered. The results of electrophysiological studies of the donor limb were generally normal.

Severing the S1 nerve root does not appear to damage the healthy limb as far as clinical assessment and electrophysiological testing can determine. Consequently, the S1 nerve can be considered to be a suitable donor nerve for reconstruction of an avulsed contralateral lumbosacral plexus.

Cite this article: Bone Joint J 2015; 97-B:358–65.


The Bone & Joint Journal
Vol. 95-B, Issue 8 | Pages 1127 - 1133
1 Aug 2013
Lama P Le Maitre CL Dolan P Tarlton JF Harding IJ Adams MA

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.