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Publications (104)
Purpose:
Gait disturbances are common in human low back pain (LBP) patients, suggesting potential applicability to rodent LBP models. This study aims to assess the influence of disc-associated LBP on gait in female Sprague Dawley rats and explore the utility of the open-source Gait Analysis Instrumentation and Technology Optimized for Rodents (GAI...
Objective
Low vagal tone is common in osteoarthritis (OA) comorbidities and results in greater peripheral inflammation. Characterizing vagal tone's role in OA pathogenesis may offer insights into OA's influences beyond the articular joint. We hypothesized that low vagal tone would accelerate onset of OA-related gait changes and worsen joint damage...
Objective
Osteoarthritis (OA) is driven by low-grade inflammation, and controlling local inflammation may offer symptomatic relief. Here, we developed an indoleamine 2,3-dioxygenase and galectin-3 fusion protein (IDO-Gal3), where IDO increases the production of local anti-inflammatory metabolites and Gal3 binds carbohydrates to extend IDO’s joint r...
Background
The purpose of this study was to evaluate if kilohertz frequency alternating current (KHFAC) stimulation of peripheral nerve could serve as a treatment for lumbar radiculopathy. Prior work shows that KHFAC stimulation can treat sciatica resulting from chronic sciatic nerve constriction. Here, we evaluate if KHFAC stimulation is also bene...
Purpose:
Exercise and physical activity are recommended to reduce pain and improve joint function in patients with knee OA. However, exercise has dose effects, with excessive exercise accelerating OA development and sedentary behaviors also promoting OA development. Prior work evaluating exercise in preclinical models has typically used prescribed...
The treatment of chronic inflammation with systemically administered anti-inflammatory treatments is associated with moderate-to-severe side effects, and the efficacy of locally administered drugs is short-lived. Here we show that inflammation can be locally suppressed by a fusion protein of the immunosuppressive enzyme indoleamine 2,3-dioxygenase...
Objective: Controlling joint inflammation can improve osteoarthritis (OA) symptoms; however, current treatments often fail to provide long-term effects. We have developed an indoleamine 2,3-dioxygenase and galectin-3 fusion protein (IDO-Gal3). IDO converts tryptophan to kynurenines, directing the local environment toward an anti-inflammatory state;...
Rodent gait analysis has emerged as a powerful, quantitative behavioral assay to characterize the pain and disability associated with movement-related disorders. In other behavioral assays, the importance of acclimation and the effect of repeated testing have been evaluated. However, for rodent gait analysis, the effects of repeated gait testing an...
Objective:
Hyaline cartilage has limited innate healing abilities and hyaline cartilage loss is a hallmark of osteoarthritis (OA). Animal models can provide important insights into cartilage regeneration potential. One such animal model, the African spiny mouse (Acomys), is capable of regenerating skin, skeletal muscle, and elastic cartilage. This...
Purpose of Review
The following review discusses the therapeutic potential of targeting the autonomic nervous system (ANS) for osteoarthritis (OA) treatment and encourages the field to consider the candidacy of bioelectronic medicine as a novel OA treatment strategy.
Recent Findings
The study of OA pathogenesis has focused on changes occurring at...
Behavioral assays of animal pain and disability can increase the clinical relevance of a preclinical study. However, pain and symptoms are difficult to measure in preclinical models. Because animals often alter their movement patterns to reduce or avoid joint pain, gait analysis can be an important tool for quantifying OA-related symptoms in rodent...
Peripheral nerve injury results in loss of motor and sensory function distal to the nerve injury and is often permanent in nerve gaps longer than 5 cm. Autologous nerve grafts (nerve autografts) utilize patients’ own nerve tissue from another part of their body to repair the defect and are the gold standard in care. However, there is a limited auto...
Background: Hypertension is a common comorbidity of osteoarthritis (OA) with known autonomic dysregulation; thus, the autonomic nervous system may provide a shared underlying mechanism. The objective of this study was to examine the role of the autonomic nervous system in a preclinical model of OA and hypertension.
Methods: Experiments were conduct...
Purpose of Review
The autonomic nervous system is an important regulator of stress responses and exhibits functional changes in chronic pain states. This review discusses potential overlap among autonomic dysregulation, osteoarthritis (OA) progression, and chronic pain. From this foundation, we then discuss preclinical to clinical research opportun...
With age, susceptibility to osteoarthritis (OA) and OA‐related pain and disability increases. Like in OA patients, gait patterns in rodent OA models shift to protect the injured limb during loading. However, unlike in OA patients, it is unknown how age affects gait changes in rodent OA models. In this study, gait compensations following meniscal in...
Changes in synovial fluid viscosity may be used to detect joint disease; however, methods to evaluate these changes at the point of care are rudimentary. Previously, we demonstrated magnetic particle translation through synovial fluid could serve as a surrogate marker of synovial fluid mechanics. In this work, the relationship of magnetic deflectio...
Innovation and entrepreneurship (I&E) programs in medical education have become available as medical schools recognize the need to train forward-thinking physicians. There is considerable diversity in the design and implementation of these curricula, which represents a challenge and possibly serves as a deterrent for the development of additional I...
Objective: Controlling joint inflammation can improve osteoarthritis (OA) symptoms; however, current treatments often fail to provide long-term effects. We have developed an indoleamine 2,3-dioxygenase and galectin-3 fusion protein (IDO-Gal3). IDO converts tryptophan to kynurenines, directing the local environment toward an anti-inflammatory state;...
Nanoparticles are under investigation as diagnostic and therapeutic agents for joint diseases, such as osteoarthritis. However, there is incomplete understanding of nanoparticle diffusion in synovial fluid, the fluid inside the joint, which consists of a mixture of the polyelectrolyte hyaluronic acid, proteins, and other components. Here, we show t...
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Chronic inflammation underlies the onset, progression and associated pain of numerous diseases.( 1 ) Current anti-inflammatory treatments administered systemically are associated with moderate-to-severe side effects, while locally administered drugs have short-lived efficacy, and neither approach successfully modifies the underlying causa...
Objective
Tissues have complex structures, comprised of solid and fluid phases. Improved understanding of interactions between joint fluid and extracellular matrix (ECM) is required in models of cartilage mechanics. X-ray photon correlation spectroscopy (XPCS) directly measures nanometer-scale dynamics and can provide insight into biofluid-biosolid...
Intra-articular injections are the most direct route for administering osteoarthritis (OA) therapies, yet how drug carriers distribute within the joint remains understudied. To this end, we developed a magnetic composite nanoparticle that can be tracked with fluorescence in vivo via an in vivo imaging system (IVIS), and quantified ex vivo via elect...
Small animal models are essential for studying anterior cruciate ligament (ACL) injury, one of the leading risk factors for post‐traumatic osteoarthritis (PTOA). Non‐surgical models of ACL rupture have recently surged as new tool to study PTOA, as they circumvent the confounding effects of surgical disruption of the joint. These models have primari...
Purpose: Synovial fluid biomarkers help evaluate osteoarthritis (OA) development. Magnetic capture, our new magnetic nanoparticle-based technology, has proven to be effective for determining extracellular matrix fragment levels in two rat OA models. Here, the feasibility of magnetic capture for detecting monocyte chemoattractant protein-1 (MCP-1 or...
Purpose: Aging is a known risk factor for osteoarthritis (OA). Several transgenic rodent models have been used to investigate the effects of accelerated or delayed aging in articular joints. However, age-effects on the progression of post-traumatic OA are less frequently evaluated. The objective of this study is to evaluate how animal age affects t...
The translational value of osteoarthritis (OA) models is often debated because numerous studies have shown that animal models frequently fail to predict the efficacy of therapies in humans. In part, this failing may be due to the paucity of preclinical studies that include behavioral assessments in their metrics. Behavioral assessments of animal OA...
Post-traumatic joint contracture (PTJC) is a debilitating condition, particularly in the elbow. Previously, we established an animal model of elbow PTJC quantifying passive post-mortem joint mechanics and histological changes temporally. These results showed persistent motion loss similar to what is experienced in humans. Functional assessment of P...
A promising treatment strategy for spinal cord injury (SCI) is to reduce inhibition from chondroitin sulfate proteoglycans (CSPGs). For example, administering intracellular σ peptide (ISP) can improve the ability of axons to cross inhibitory CSPGs and improve function in rodent models of SCI. To translate such treatments into the clinic, we need ro...
Objective:
In osteoarthritis (OA) models, histology is commonly used to evaluate the severity of joint damage. Unfortunately, semi-quantitative histological grading systems include some level of subjectivity, and quantitative grading systems can be tedious to implement. The objective of this work is to introduce an open source, graphic user interf...
Locomotive changes are often associated with disease or injury, and these changes can be quantified through gait analysis. Gait analysis has been applied to preclinical studies, providing quantitative behavioural assessment with a reasonable clinical analogue. However, available gait analysis technology for small animals is somewhat limited. Furthe...
Background
Rodent gait analysis provides robust, quantitative results for preclinical musculoskeletal and neurological models. In prior work, surgical models of osteoarthritis have been found to result in a hind limb shuffle-stepping gait compensation, while a high dose monoiodoacetate (MIA, 3 mg) model resulted in a hind limb antalgic gait. Howeve...
Objective:
To assess changes in orofacial tactile sensitivity and gnawing related to capsaicin-mediated cutaneous, myogenic, and arthrogenic nociception in the rat.
Design:
After recovery from anesthesia, orofacial tactile sensitivity and gnawing were assessed using operant testing methods following capsaicin application. Twenty female CD-Hairle...
Objectives:
To investigate and discuss the effects of cocoa on orofacial pain.
Setting and sample population:
The Department of Orthodontics at the University of Florida (UF). Male and female hairless rats (N=20/group) were tested.
Materials and methods:
Rats were tested using the Orofacial Pain Assessment Device (OPAD) before and after changi...
Biodegradable Mg alloys have the potential to replace currently used metallic medical implant devices, likely eliminating toxicity concerns and the need for secondary surgeries, while also providing a potentially stimulating environment for tissue growth. A recently developed Mg-Ca-Sr alloy possesses advantageous characteristics over other Mg alloy...
Objective:
Parallel measures of OA pathogenesis across species can help researchers evaluate OA models relative to the human condition. Toward this need, our group recently developed a magnetic nanoparticle-based technology, termed magnetic capture, to analyze biomarkers within a rat knee. The objectives of this study were two-fold: 1) directly co...
Objective:
In rodent osteoarthritis models, behavioral changes are often subtle and require highly sensitive methods to detect these changes. Gait analysis is one assay that may provide sensitive, quantitative measurement of these behavioral changes(1). To increase detection sensitivity of gait assessments relative to spatiotemporal gait collectio...
Aim of the study:
The importance of the medial meniscus to knee health is demonstrated by studies which show meniscus injuries significantly increase the likelihood of developing osteoarthritis (OA), and knee OA can be modeled in rodents using simulated meniscus injuries. Traditionally, histological assessments of OA in these models have focused o...
While rodent gait analysis can quantify the behavioral consequences of disease, significant methodological differences exist between analysis platforms and little validation has been performed to understand or mitigate these sources of variance. By providing the algorithms used to quantify gait, open-source gait analysis software can be validated a...
Gait analysis is a useful tool to understand behavioral changes in preclinical arthritis models. While observational scoring and spatiotemporal gait parameters are the most widely performed gait analyses in rodents, commercially available systems can now provide quantitative assessments of spatiotemporal patterns. However, inconsistencies remain be...
Since the meniscus has limited capacity to self-repair, creating a viable meniscus replacement may help reduce the incidence of OA after meniscus damage. As a first step toward this goal, this study evaluated the mechanical integrity of a decellularized, laser drilled meniscus as a potential scaffold for meniscal engineering. To evaluate the decell...
Biodegradable magnesium (Mg) alloys combine the advantages of traditional metallic implants and biodegradable polymers, having high strength, low density, and a stiffness ideal for bone fracture fixation. A recently developed Mg-Ca-Sr alloy potentially possesses advantageous characteristics over other Mg alloys, such as slower degradation rates and...
As research progresses to find a suitable knee meniscus replacement, accurate in vitro testing becomes critical for feasibility and comparison studies of mechanical integrity. Within the knee, the meniscus is bathed in synovial fluid, yet the most common hydration fluid in laboratory testing is phosphate buffered saline (PBS). PBS is a relatively s...
After transection of the medial collateral ligament and medial meniscus (MCLT + MMT) in the rat, focal cartilage lesions develop over 4–6 weeks; however, sham surgery (MCLT alone) does not result in cartilage damage over a similar period. Thus, comparison of MCLT + MMT with the MCLT sham group offers an opportunity to investigate behavioral modific...
This paper investigates the practicality of using a small, permanent magnet to capture magnetic particles out of high-viscosity biological fluids, such as synovial fluid.
Numerical simulations are used to predict the trajectory of magnetic particles toward the permanent magnet. The simulations are used to determine a "collection volume" with a time...
Biomarker development for osteoarthritis (OA) often begins in rodent models, but can be limited by an inability to aspirate synovial fluid from a rodent stifle (similar to the human knee). To address this limitation, we have developed a magnetic nanoparticle-based technology to collect biomarkers from a rodent stifle, termed magnetic capture. Using...
Patients with osteoarthritis (OA) primarily seek treatment due to pain and disability, yet the primary endpoints for rodent OA models tend to be histological measures of joint destruction. The discrepancy between clinical and preclinical evaluations is problematic, given that radiographic evidence of OA in humans does not always correlate to the se...
In this paper, the collection of magnetic particles from synovial fluid using Nd-Fe-B micromagnets is quantitatively studied to determine the influence of fluid viscosity and magnet geometry on the velocity distribution and collection rate. Magnetic capture is validated in highly viscous fluids, such as bovine synovial fluid (η∼ 1 Pa·s). A first-or...
Osteoarthritis (OA), a degenerative joint disease, is a large and quickly growing socioeconomic burden. Disease-modifying drugs are not available for symptomatic OA, and detection of early, asymptomatic OA presents a significant challenge. Molecular biomarkers found in the joint's synovial fluid (SF) have demonstrated a significant potential for ea...
Approximately 2.6 % of the US population visits a physician for treatment of spinal disorders annually (Fraser 2009) with costs of $7.1 billion from lost work days alone (Ricci et al. 2006). “Herniation” of the intervertebral disc is one of the several spinal disorders that contribute to this very high incidence, with potential to cause significant...
Intervertebral disc herniation may contribute to inflammatory processes that associate with radicular pain and motor deficits. Molecular changes at the affected dorsal root ganglion (DRG), spinal cord, and even midbrain, have been documented in rat models of radiculopathy or nerve injury. The objective of this study was to evaluate gait and the exp...
Osteoarthritis (OA) results in pain and disability; however, preclinical OA models often focus on joint-level changes. Gait analysis is one method used to evaluate both preclinical OA models and OA patients. The objective of this study is to describe spatiotemporal and ground reaction force changes in a rat medial meniscus transection (MMT) model o...
Tumor necrosis factor-α (TNFα) has received significant attention as a mediator of lumbar radiculopathy, with interest in TNF antagonism to treat radiculopathy. Prior studies have demonstrated that TNF antagonists can attenuate heightened nociception resulting from lumbar radiculopathy in the preclinical model. Less is known about the potential imp...
Interleukin-1 beta (IL1β) is a proinflammatory cytokine that mediates arthritic pathologies. Our objectives were to evaluate pain and limb dysfunction resulting from IL1β over-expression in the rat knee and to investigate the ability of local IL1 receptor antagonist (IL1Ra) delivery to reverse-associated pathology. IL1β over-expression was induced...
Interleukin-17 (IL-17) is a cytokine recently shown to be elevated, along with interferon-γ (IFNγ) and tumor necrosis factor (TNFα), in degenerated and herniated intervertebral disc (IVD) tissues, suggesting a role for these cytokines in intervertebral disc disease. The objective of our study was to investigate the involvement of IL-17 and costimul...
Osteoarthritis (OA) is a degenerative joint disease that can result in joint pain, loss of joint function, and deleterious effects on activity levels and lifestyle habits. Current therapies for OA are largely aimed at symptomatic relief and may have limited effects on the underlying cascade of joint degradation. Local drug delivery strategies may p...
In mice with Col9a1 gene inactivation (Col9a1(-/-)), osteoarthritis (OA) and intervertebral disc degeneration develop prematurely. The aim of this study was to investigate Col9a1(-/-) mice for functional and symptomatic changes that may be associated with these pathologies.
Col9a1(-/-) and wild-type mice were investigated for reflexes, functional i...
The authors investigated gait abnormalities and mechanical hypersensitivity associated with invertebral disc herniation in a rat model of radiculopathy. Further evaluation involved assessing how nucleus pulposus (NP) injury affected systemic cytokine expression and molecular changes at the dorsal root ganglion (DRG).
The objective of this work was...