Chemokine profile of disc degeneration with acute or chronic pain.

OBJECT: Disc-related disorders such as herniation and chronic degenerative disc disease (DDD) are often accompanied by acute or chronic pain. Different mediators have been identified in the development of radicular pain and DDD. Previous studies have not analyzed individual cytokine profiles discriminating between acute sciatic and chronic painful conditions, nor have they distinguished between different anatomical locations within the disc. The aim of this study was to elucidate the protein biochemical mechanisms in DDD. METHODS: The authors determined expression levels of matrix metalloproteinase-3, transforming growth factor-ß (TGF-ß), tumor necrosis factor-α, interleukin-1α, and pro-substance P using enzyme-linked immunosorbent assay and Western blot analyses in patients suffering from DDD (n = 7), acute back pain due to herniated discs with radiculopathy (n = 7), and a control group (n = 7). Disc tissue samples from the anulus fibrosus (AF) and nucleus pulposus (NP) were analyzed. Statistical analysis was performed using nonparametric tests. RESULTS: A distinct distribution of cytokines was found in different anatomical regions of intervertebral discs in patients with DDD and herniated NP. Increased TGF-ß levels were predominantly found in DDD. Matrix metalloproteinase-3 was increased in acute herniated disc material. Increased levels of substance P were found in patients suffering from DDD but not in patients with disc herniation. The data showed significantly higher levels of proinflammatory cytokines in the AF and NP of patients with DDD, and the expression levels in the AF were even higher than in the NP, suggesting that the inflammatory response initiates from the AF. CONCLUSIONS: These results highlight the complex mechanisms involved during disc degeneration and the need to distinguish between acute and chronic processes as well as different anatomical regions, namely the AF and NP. They also highlight potential problems in disc nucleus replacement therapies because the results suggest a biochemical link between AF and NP cytokine expression.

Percutaneous instrumentation of the cervical and cervico-thoracic spine using pedicle screws: preliminary clinical results and analysis of accuracy.

The pedicle screw instrumentation represents the most rigid construct of the cervical and cervicothoracic spine and in spite of the risks to neurovascular structures clinical relevant complications do not occur frequently. The steep angles of the cervical pedicles result in a wide surgical exposure with extensive muscular trauma. The objective of this study was the evaluation of the accuracy of cervical pedicle screw insertion through a minimally invasive technique to reduce access-related muscular trauma. Therefore, percutaneous transpedicular instrumentation of the cervical and cervicothoracic spine was performed in 15 patients using fluoroscopy. All instrumentations from C2 to Th4 were inserted bilaterally through 2 to 3-cm skin and fascia incisions even in multilevel procedures and the rods were placed by blunt insertion through the incision. Thin-cut CT scan was used postoperatively to analyze pedicle violations. 76.4% of 72 screws were placed accurately. Most pedicle perforations were seen laterally towards the vertebral artery. Critical breaches >2 mm or narrowing of the transversal foramen occurred in 12.5% of screws; however, no revision surgery for screw displacement was needed in the absence of clinical symptoms. No conversion from percutaneous to open surgery was necessary. It was concluded that percutaneous transpedicular instrumentation of the cervical spine is a surgically demanding technique and should be reserved for experienced spine surgeons. The indications are limited to instrumentation-only procedures or in combination with anterior treatment, but with the potential to minimize access-related morbidity.

Sequential changes in vessel formation and micro-vascular function during bone repair.

BACKGROUND: Angiogenesis, the process of new vessel formation from a pre-existing vascular network, is essential for bone development and repair. New vessel formation and microvascular functions are crucial during bone repair, not only for sufficient nutrient supply, transport of macromolecules and invading cells, but also because they govern the metabolic microenvironment. Despite its central role, very little is known about the initial processes of vessel formation and microvascular function during bone repair. METHODS: To visualize and quantify the process of vessel formation and microvascular function during bone repair, we transplanted neonatal femora with a substantial defect into dorsal skin-fold chambers in severe combined immunodeficient (SCID) mice for continuous noninvasive in-vivo evaluation. We employed intravital microscopic techniques to monitor effective microvascular permeability, functional vascular density, blood flow rate and leukocyte flux repeatedly over 16 days. Oxytetracyclin and v. Kossa/v. Giesson staining was performed to quantify the calcification process in vivo and in vitro. RESULTS: Development of a hematoma surrounding the defect area was the initial event, which was accompanied by a significant increase in microvascular permeability and blood flow rate. With absorption of the hematoma and vessel maturation, permeability decreased continuously, while vascular density and tissue perfusion increased. Histological evaluation revealed that the remodeling of the substantial defect prolonged the in-vivo monitored calcification process. INTERPRETATION: The size of the initial substantial defect correlated positively with increased permeability, suggesting improved release of permeability-inducing cytokines. The unchanged permeability in the control group with boiled bones and a substantial defect corroborated these findings. The adaptation to increasing metabolic demands was initially mediated by increased blood flow rate, later with increasing vascular density through increased tissue perfusion rate. These insights into the sequence of microvascular alterations may assist in the development of targeted drug delivery therapies and caution against the use of permeability-altering drugs during bone healing.