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A novel experimental knee-pain model affects perceived pain and movement biomechanics.

ABSTRACT: CONTEXT: Knee injuries are prevalent, and the associated knee pain is linked to disability. The influence of knee pain on movement biomechanics, independent of other factors related to knee injuries, is difficult to study and unclear. OBJECTIVE: (1) To evaluate a novel experimental knee-pain model and (2) better understand the independent effects of knee pain on walking and running biomechanics. DESIGN: Crossover study. SETTING: Biomechanics laboratory. PATIENTS OR OTHER PARTICIPANTS: Twelve able-bodied volunteers (age = 23 ± 3 years, height = 1.73 ± 0.09 m, mass = 75 ± 14 kg). INTERVENTION(S): Participants walked and ran at 3 time intervals (preinfusion, infusion, and postinfusion) for 3 experimental conditions (control, sham, and pain). During the infusion time interval for the pain and sham conditions, hypertonic or isotonic saline, respectively, was continuously infused into the right infrapatellar fat pad for 22 minutes. MAIN OUTCOME MEASURE(S): We used repeated-measures analyses of variance to evaluate the effects of time and condition on (1) perceived knee pain and (2) key biomechanical characteristics (ground reaction forces, and joint kinematics and kinetics) of walking and running (P < .05). RESULTS: The hypertonic saline infusion (1) increased perceived knee pain throughout the infusion and (2) reduced discrete characteristics of each component of the walking ground reaction force, walking peak plantar-flexion angle (range = 62°-67°), walking peak plantar-flexion moment (range = 95-104 N·m), walking peak knee-extension moment (range = 36-49 N·m), walking peak hip-abduction moment (range = 62-73 N·m), walking peak support moment (range = 178-207 N·m), running peak plantar-flexion angle (range = 38°-77°), and running peak hip-adduction angle (range = 5-21°). CONCLUSIONS: This novel experimental knee pain model consistently increased perceived pain during various human movements and produced altered running and walking biomechanics that may cause abnormal knee joint-loading patterns.

SUBMITTER: Seeley MK

PROVIDER: S-EPMC3655747 | biostudies-other | 2013 May-Jun

REPOSITORIES: biostudies-other

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Project description:OBJECTIVE: To analyze genome-wide changes in chondrocyte gene expression in a surgically induced model of early osteoarthritis (OA) in rats, to assess the similarity of this model to human OA, and to identify genes and mechanisms leading to OA pathogenesis. METHODS: OA was surgically induced in 5 rats by anterior cruciate ligament transection and partial medial meniscectomy. Sham surgery was performed in 5 additional animals, which were used as controls. Both groups underwent 4 weeks of forced mobilization, 3 times per week. RNA was extracted directly from articular chondrocytes in the OA (operated), contralateral, and sham-operated knees. Affymetrix GeneChip expression arrays were used to assess genome-wide changes in gene expression. Expression patterns of selected dysregulated genes, including Col2a1, Mmp13, Adamts5, Ctsc, Ptges, and Cxcr4, were validated by real-time polymerase chain reaction, immunofluorescence, or immunohistochemistry 2, 4, and 8 weeks after surgery. RESULTS: After normalization, comparison of OA and sham-operated samples showed 1,619 differentially expressed probe sets with changes in their levels of expression >/=1.5-fold, 722 with changes >/=2-fold, 135 with changes >/=4-fold, and 20 with changes of 8-fold. Dysregulated genes known to be involved in human OA included Mmp13, Adamts5, and Ptgs2, among others. Several dysregulated genes (e.g., Reln, Phex, and Ltbp2) had been identified in our earlier microarray study of hypertrophic chondrocyte differentiation. Other genes involved in cytokine and chemokine signaling, including Cxcr4 and Ccl2, were identified. Changes in gene expression were also observed in the contralateral knee, validating the sham operation as the appropriate control. CONCLUSION: Our results demonstrate that the animal model mimics gene expression changes seen in human OA, supporting the relevance of newly identified genes and pathways to early human OA. We propose new avenues for OA pathogenesis research and potential targets for novel OA treatments, including cathepsins and cytokine, chemokine, and growth factor signaling pathways, in addition to factors controlling the progression of chondrocyte differentiation. Experiment Overall Design: OA was surgically induced in 5 rats by anterior cruciate ligament transection and partial medial meniscectomy. Sham surgery was performed in 5 additional animals, which were used as controls. Both groups underwent 4 weeks of forced mobilization, 3 times per week. RNA was extracted directly from articular chondrocytes in the OA (operated), contralateral, and sham-operated knees, 28 days post-surgery. Affymetrix GeneChip expression arrays were used to assess genome-wide changes in gene expression.

Project description:Virtual representations of the knee joint can provide clinicians, scientists, and engineers the tools to explore mechanical functions of the knee and its tissue structures in health and disease. Modeling and simulation approaches such as finite element analysis also provide the possibility to understand the influence of surgical procedures and implants on joint stresses and tissue deformations. A large number of knee joint models are described in the biomechanics literature. However, freely accessible, customizable, and easy-to-use models are scarce. Availability of such models can accelerate clinical translation of simulations, where labor-intensive reproduction of model development steps can be avoided. Interested parties can immediately utilize readily available models for scientific discovery and clinical care. Motivated by this gap, this study aims to describe an open source and freely available finite element representation of the tibiofemoral joint, namely Open Knee, which includes the detailed anatomical representation of the joint's major tissue structures and their nonlinear mechanical properties and interactions. Three use cases illustrate customization potential of the model, its predictive capacity, and its scientific and clinical utility: prediction of joint movements during passive flexion, examining the role of meniscectomy on contact mechanics and joint movements, and understanding anterior cruciate ligament mechanics. A summary of scientific and clinically directed studies conducted by other investigators are also provided. The utilization of this open source model by groups other than its developers emphasizes the premise of model sharing as an accelerator of simulation-based medicine. Finally, the imminent need to develop next-generation knee models is noted. These are anticipated to incorporate individualized anatomy and tissue properties supported by specimen-specific joint mechanics data for evaluation, all acquired in vitro from varying age groups and pathological states.

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A novel experimental knee-pain model affects perceived pain and movement biomechanics.

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