Objective. To verify the biologic links between progressive cellular and structural alterations within knee joint components and development of symptomatic chronic pain that are characteristic of osteoarthritis (OA), and to investigate the molecular basis of alterations in nociceptive pathways caused by OA-induced pain.Methods. An animal model of knee joint OA pain was generated by intraarticular injection of monoiodoacetate (MIA) in Sprague-Dawley rats, and symptomatic pain behavior tests were performed. Relationships between development of OA with accompanying pain responses and gradual alterations in cellular and structural knee joint components (i.e., cartilage, synovium, meniscus, subchondral bone) were examined by histologic and immunohistologic analysis, microscopic examination, and microfocal computed tomography. Progressive changes in the dynamic interrelationships between peripheral knee joint tissue and central components of nociceptive pathways caused by OA-induced pain were examined by investigating cytokine production and expression in sensory neurons of the dorsal root ganglion and spinal cord.Results. We observed that structural changes in components of the peripheral knee joint correlate with alterations in the central compartments (dorsal root ganglia and the spinal cord) and symptomatic pain assessed by behavioral hyperalgesia. Our comparative gene expression studies revealed that the pain pathways in MIA-induced knee OA may overlap, at least in part, with neuropathic pain mechanisms. Similar results were also observed upon destabilization of the knee joint in the anterior cruciate ligament transection and destabilization of the medial meniscus models of OA.Conclusion. Our results indicate that MIAinduced joint degeneration in rats generates an animal model that is suitable for mechanistic and pharmacologic studies on nociceptive pain pathways caused by OA, and provide key in vivo evidence that OA pain is caused by central sensitization through communication between peripheral OA nociceptors and the central sensory system. Furthermore, our data suggest a mechanistic overlap between OA-induced pain and neuropathic pain.

Objective The current study was undertaken to adapt Equilibrium Partitioning of an Ionic Contrast agent via microcomputed tomography (EPIC-µCT) to mouse articular cartilage, which presents a particular challenge because it is thin (~30 µm) and has a small volume (0.2 – 0.4 mm3), meaning there is only approximately 2 – 4 µg of chondroitin sulfate glycosaminoglycan per joint surface cartilage. Design Using 6 µm isotropic voxels and the negatively charged contrast agent ioxaglate (Hexabrix), we optimized contrast agent concentration and incubation time, assessed two methods of tissue preservation (formalin fixation and freezing), examined the effect of ex vivo chondroitinase ABC digestion on x-ray attenuation, assessed accuracy and precision, compared young and skeletally mature cartilage, and determined patterns of degradation in a murine cartilage damage model induced by treadmill running. Results The optimal concentration of the contrast agent was 15%, formalin fixation was preferred to freezing, and 2 hours of incubation was needed to reach contrast agent equilibrium with formalin fixed specimens. There was good agreement with histologic measurements of cartilage thickness, although µCT overestimated thickness by 13% (~5 µm) in 6 week old mice. Enzymatic release of 0.8 µg of choindrotin sulfate (about 40% of the total) increased x-ray attenuation by ~17%. There was a 15% increase in x-ray attenuation in 14 week old mice compared to 6 week old mice (p < 0.001) and this corresponded to ~65% decrease in chondroitin sulfate content at 14 weeks. The older mice also had reductions of 33% in cartilage thickness and 44% in cartilage volume (p < 0.001). Treadmill running induced a 16% decrease in cartilage thickness (p = 0.012) and a 12% increase in x-ray attenuation (p = 0.006) in 14 week old mice. Conclusion This technique enables non-destructive visualization and quantification of murine femoral articular cartilage in three dimensions with anatomic specificity and should prove to be a useful new tool in studying degeneration of cartilage in mouse models.

Age, sex, overbite, overjet, and anterior linear contact are compared as indicators of biting force. F scores and correlation coefficients indicate a correlation of age, sex, overbite, and anterior linear contact with biting force.

Quantitative knowledge of lumbar facet joint morphology is crucial in understanding the relationship between the geometry and kinematics of the facet joint as well as better understanding degenerative changes. Accurate prediction of lumbar facet joint contact area and stresses requires 3D representation of the thickness distribution of the articular cartilage of the facet joint. Several groups have reported on cervical facet joint cartilage thickness measurements using different approaches [2,3]. To the best of our knowledge, three-dimensional (3D) distribution of lumbar facet joint cartilage thickness has not been reported. Current methods of measuring various geometrical parameters of facet joint cartilage usually utilize high resolution magnetic resonance (MR) imaging techniques. Although these techniques represent the most up-to-date advanced methods in the soft tissue imaging field, facet joint cartilage reconstruction cannot be accomplished with reasonable fidelity using this approach. A study by Koo et al. [1] on knee joint cartilage showed that the accuracy of cartilage thickness measurement in the cartilage models derived from MRI (1.5T) varies with cartilage thickness. This study reported accurate measurements only for cartilage whose thickness ranged from 2.5 mm to 3.3 mm, which is in the range larger than the average lumbar facet joint cartilage assumed to be around 0.8 mm. Therefore, the objective of this study was to 1) analyze 3D lumbar facet joint cartilage thickness distributions based on laser scanner data, 2) compare this method using μCT and 3T MRI.