Summary. Cytokines produced within the degenerate disc induce expression of neurotrophic factors and pain related peptides which could be important in nerve ingrowth and pain sensitisation leading to low back pain. The intervertebral disc (IVD) is considered the largest aneural and avascular structure within the human body, yet during degeneration vascularisation of the IVD is seen to be accompanied by nociceptive nerves. Low back pain is a highly debilitating condition affecting around 80% of the population, 40% of which are attributed to IVD degeneration.
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
Posterior fixation of intervertebral discs is used to treat, and occasionally diagnose,
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
Introduction.
It has been thought that lumbar intervertebral discs were innervated segmentally. We have previously shown that the L5-L6 intervertebral disc in the rat is innervated bilaterally from the L1 and L2 dorsal root ganglia through the paravertebral sympathetic trunks, but the pathways between the disc and the paravertebral sympathetic trunks were unknown. We have now studied the spines of 17 rats to elucidate the exact pathways. We examined serial sections of the lumbar spine using immunohistochemistry for calcitonin gene-related peptide, a sensory nerve marker. We showed that these nerve fibres from the intervertebral disc ran through the sinuvertebral nerve into the rami communicantes, not into the corresponding segmental spinal nerve. In the rat, sensory information from the lumbar intervertebral discs is conducted through rami communicantes. If this innervation pattern applies to man, simple decompression of the corresponding nerve root will not relieve
Introduction. Severe ‘discogenic’ back pain may be related to the ingrowth of nerves and blood vessels, although this is controversial. We hypothesise that ingrowth is greater in painful discs, and is facilitated in the region of annulus fissures. Methods. We compared tissue removed at surgery from 22 patients with
To clarify the pathomechanisms of discogenic low back pain, the sympathetic afferent discharge originating from the L5-L6 disc via the L2 root were investigated neurophysiologically in 31 Lewis rats. Sympathetic afferent units were recorded from the L2 root connected to the lumbar sympathetic trunk by rami communicantes. The L5-L6 discs were mechanically probed, stimulated electrically to evoke action potentials and, finally, treated with chemicals to produce an inflammatory reaction. We could not obtain a response from any units in the L5-L6 discs using mechanical stimulation, but with electrical stimulation we identified 42 units consisting mostly of A-delta fibres. In some experiments a response to mechanical probing of the L5-L6 disc was recognised after producing an inflammatory reaction. This study suggests that mechanical stimulation of the lumbar discs may not always produce pain, whereas inflammatory changes may cause the disc to become sensitive to mechanical stimuli, resulting in nociceptive information being transmitted as discogenic low back pain to the spinal cord through the lumbar sympathetic trunk. This may partly explain the variation in human symptoms of degenerate discs.
Interleukin 18 (IL-18) is a regulatory cytokine that degrades the disc matrix. Bone morphogenetic protein-2 (BMP-2) stimulates synthesis of the disc extracellular matrix. However, the combined effects of BMP-2 and IL-18 on human intervertebral disc degeneration have not previously been reported. The aim of this study was to investigate the effects of the anabolic cytokine BMP-2 and the catabolic cytokine IL-18 on human nucleus pulposus (NP) and annulus fibrosus (AF) cells and, therefore, to identify potential therapeutic and clinical benefits of recombinant human (rh)BMP-2 in intervertebral disc degeneration. Levels of IL-18 were measured in the blood of patients with intervertebral disc degenerative disease and in control patients. Human NP and AF cells were cultured in a NP cell medium and treated with IL-18 or IL-18 plus BMP-2. mRNA levels of target genes were measured by real-time polymerase chain reaction, and protein levels of aggrecan, type II collagen, SOX6, and matrix metalloproteinase 13 (MMP13) were assessed by western blot analysis.Objectives
Methods
In a study on ten fresh human cadavers we examined the change in the height of the intervertebral disc space, the angle of lordosis and the geometry of the facet joints after insertion of intervertebral total disc replacements. SB III Charité prostheses were inserted at L3-4, L4-5, and L5-S1. The changes studied were measured using computer navigation sofware applied to CT scans before and after instrumentation. After disc replacement the mean lumbar disc height was doubled (p <
0.001). The mean angle of lordosis and the facet joint space increased by a statistically significant extent (p <
0.005 and p = 0.006, respectively). By contrast, the mean facet joint overlap was significantly reduced (p <
0.001). Our study indicates that the increase in the intervertebral disc height after disc replacement changes the geometry at the facet joints. This may have clinical relevance.