Intervertebral disc (IVD) degeneration is a major cause of low back pain. The transcription factor c-Fos/Activator Protein-1 (AP-1) controls the expression of inflammatory cytokines and matrix metalloproteinases (MMPs) that contribute to the pathogenesis IVD degeneration. We investigated the effects of inhibition of c-Fos/AP-1 on IVD degeneration and associated pain. A selective inhibitor, T-5224, significantly suppressed the interleukin-1β-induced up-regulation ofMmp-3, Mmp-13andAdamts-5transcription in human nucleus pulposus cells and in a mouse explant culture model of IVD degeneration. We used a tail disc percutaneous needle puncture method to further assess the effects of oral administration of T-5224 on IVD degeneration. Analysis of disc height, T2-magnetic resonance imaging (MRI) findings, and histology revealed that IVD degeneration was significantly mitigated by T-5224. Further, oral administration of T-5224 ameliorated pain as indicated by the extended tail-flick latency in response to heat stimulation of rats with needle-puncture-induced IVD degeneration. These findings suggest that the inhibition of c-Fos/AP-1 prevents disc degeneration and its associated pain and that T-5224 may serve as a drug for the prevention of IVD degeneration.

Ossification of the posterior longitudinal ligament (OPLL) is characterized by replacement of ligamentous tissue by ectopic new bone formation. OPLL causes narrowing of the spinal canal, resulting in neurological impairment. However, the pathogenesis of OPLL has not been fully elucidated. We investigated whether inflammation occurs in OPLL or not using high-sensitivity CRP (hs-CRP) in a case-control study. This study included 103 patients with OPLL in the patient group and 95 age- and sex-matched volunteers with degenerative spinal disease in the control group. Of the 103 OPLL patients, 88 patients who were available for more than 2 years follow-up were checked for OPLL progression. A blood sample was obtained and Hs-CRP, and other routine data, including total protein (TP), albumin (ALB), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), glucose (Glu), calcium (Ca), inorganic phosphate (Pi), white blood cell count (WBC), hemoglobin (Hb) and platelet (PLT), were analyzed. The data were compared between the patients with OPLL and the controls. The severity of the ossified lesions in the whole spine were evaluated by the ossification index (OS index) in patients with OPLL. The data were also compared between the patients with OPLL progression (the progression group) and the patients without OPLL progression (the non-progression group). In the results, the mean hs-CRP in the OPLL group was higher than that in the controls. The Pi in the OPLL group was lower than that in the control group. A negative correlation was found between the Pi and the OS index. The mean hs-CRP in the progression group was higher than that in the non-progression group. There was a positive correlation between the average length of the OPLL progression per year and the hs-CRP. The results may suggest the occurrence of local inflammation in OPLL and the inflammation might cause OPLL progression. These facts are important for understanding the pathology of OPLL.

Lumbar epidural lipomatosis (LEL) is characterized by abnormal accumulation of unencapsulated adipose tissue in the spinal epidural space. Such accumulation compresses the dural sac and nerve roots, and results in various neurological findings. However, the pathophysiology of LEL remains unclear. This study examined the associations between imaging and clinical findings in detail, and investigated the mechanisms underlying symptom onset by measuring intraoperative epidural pressures in LEL. Sixteen patients (all men; mean age, 68.8 years) were enrolled between 2011 and 2015. Mean body mass index was 26.5 kg/m2. Four cases were steroid-induced, and the remaining 12 cases were idiopathic. All patients presented with neurological deficits in the lower extremities. Cauda equina syndrome (CES) alone was seen in 8 patients, radiculopathy alone in 4, and both radiculopathy and CES (mixed CES) in 4. All patients subsequently underwent laminectomy with epidural lipomatosis resection and were followed-up for more than 1 year. We investigated the clinical course and imaging and measured epidural pressures during surgery. Subjective symptoms improved within 1 week after surgery. Mean Japanese Orthopaedic Association (JOA) score was 15.2 ± 2.8 before surgery, improving to 25.4 ± 2.5 at 1 year after surgery. On magnetic resonance imaging, all lipomatosis lesions included the L4–5 level. On preoperative computed tomography, saucerization of the laminae was not observed in radiculopathy cases, whereas saucerization of the posterior vertebral body was observed in all radiculopathy or mixed CES cases. Intraoperative epidural pressures were significantly higher than preoperative subarachnoid pressures. The results suggest that high epidural pressure resulting from the proliferation of adipose tissue leads to saucerization of the lumbar spine and subsequent symptoms. Clinical courses were satisfactory after laminectomy. In LEL, epidural pressure increases and symptoms develop through the abnormal proliferation of adipose tissue. Higher epidural pressures induce saucerization of the laminae and/or posterior vertebral body. Furthermore, the direction of proliferative adipose tissue (i.e., site of saucerization) might be related to the types of neurological symptoms.