Intradiscal inflammatory stimulation induces spinal pain behavior and intervertebral disc degeneration in vivo.

Degeneration of the intervertebral disc (IVD) results in a range of symptomatic (i.e., painful) and asymptomatic experiences. Components of the degenerative environment, including structural disruption and inflammatory cytokine production, often correlate with pain severity. However, the role of inflammation in the activation of pain and degenerative changes has been complex to delineate. The most common IVD injury model is puncture; however, it initiates structural damage that is not representative of the natural degenerative cascade. In this study, we utilized in vivo injection of lipopolysaccharide (LPS), a pro-inflammatory stimulus, into rat caudal IVDs using 33G needles to induce inflammatory activation without the physical tissue disruption caused by puncture using larger needles. LPS injection increased gene expression of pro-inflammatory cytokines (Tnfa, Il1b) and macrophage markers (Inos, Arg1), supported by immunostaining of macrophages (CD68, CCR7, Arg1) and systemic changes in blood cytokine and chemokine levels. Disruption of the IVD structural integrity after LPS injection was also evident through changes in histological grading, disc height, and ECM biochemistry. Ultimately, intradiscal inflammatory stimulation led to local mechanical hyperalgesia, demonstrating that pain can be initiated by inflammatory stimulation of the IVD. Gene expression of nociceptive markers (Ngf, Bdnf, Cgrp) and immunostaining for neuron ingrowth (PGP9.5) and sensitization (CGRP) in the IVD were also shown, suggesting a mechanism for the pain exhibited. To our knowledge, this rat IVD injury model is the first to demonstrate local pain behavior resulting from inflammatory stimulation of caudal IVDs. Future studies will examine the mechanistic contributions of inflammation in mediating pain.

Coaxial extendible knee equalizes limb length in children with osteogenic sarcoma.

We assessed our ability to achieve limb length equality (LLE) in children following limb-sparing surgery for distal femur osteogenic sarcoma using coaxial extendible prostheses in 12 children, averaging 11.6 years old at the time of tumor resection (range, 5.9-15.5 years). All but one child achieved clinical limb length equality. There were 23 extensions, averaging 3.8 extensions per patient (range, 1-5), by an average 13 mm per extension and an average total extension of 49.3 mm per patient extended. Eight children underwent revision surgery after an average of 45.1 months (range, 3-115 months). Aseptic loosening occurred more frequently among children with greater femoral diameter growth. The overall prosthetic survival was 60% at 3 years and 35% at 5 years. The survival until aseptic loosening at 3 and 5 years was 85% and 45%, respectively. Press-fit components survived longer than cemented stems. None of the devices loosened. At skeletal maturity the MSTS functional scores averaged 25. Using a coaxial extendible implant, we efficiently achieved LLE in this population. Prosthetic revision was needed frequently. Younger age and longer resection percentages were associated with shorter prosthetic survival and higher revision/aseptic loosening rates. Femoral diameter growth may contribute to loosening. Early experience with this extendible implant is promising.