Aging is associated with impairment in postural control in humans. While dogs are a powerful model for the study of aging, the associations between age and postural control in this species have not ...yet been elucidated. The aims of this work were to establish a reliable protocol to measure center of pressure excursions in standing dogs and to determine age-related changes in postural sway. Data were obtained from 40 healthy adult dogs (Group A) and 28 senior dogs (Group B) during seven trials (within one session of data collection) of quiet standing on a pressure sensitive walkway system. Velocity, acceleration, root mean square, 95% ellipse area, range and frequency revolve were recorded as measures of postural sway. In Group A, reliability was assessed with intraclass correlation, and the effect of morphometric variables was evaluated using linear regression. By means of stepwise linear regression we determined that root mean square overall and acceleration in the craniocaudal direction were the best variables able to discriminate between Group A and Group B. The relationship between these two center-of-pressure (COP) measures and the dogs’ fractional lifespan was examined in both groups and the role of pain and proprioceptive deficits was evaluated in Group B. All measures except for frequency revolve showed good to excellent reliability. Weight, height and length were correlated with most of the measures. Fractional lifespan impacted postural control in Group B but not Group A. Joint pain and its interaction with proprioceptive deficits influence postural sway especially in the acceleration in the craniocaudal direction, while fractional lifespan was most important in the overall COP displacement. In conclusion, our study found that pressure sensitive walkway systems are a reliable tool to evaluate postural sway in dogs; and that postural sway is affected by morphometric parameters and increases with age and joint pain.
Relatively little work has evaluated both the disease of osteoarthritis (OA) and clinically-relevant pain outcome measures across different OA models in rats. The objective of this study was to ...compare sensitivity, pain, and histological disease severity across chemical and surgical models of OA in the rat. Stifle OA was induced in Sprague-Dawley rats via intraarticular injection of monoiodoacetate (MIA) or surgical transection of anterior cruciate ligament and/or destabilization of medial meniscus (ACL+DMM or DMM alone). Reflexive (e.g., mechanical and thermal stimuli) measures of sensitivity and non-reflexive assays (e.g., lameness, static hindlimb weight-bearing asymmetry, dynamic gait analysis) of pain were measured over time. Joint degeneration was assessed histologically. Six-weeks post OA-induction, the ACL+DMM animals had significantly greater visually observed lameness than MIA animals; however, both ACL+DMM and MIA animals showed equal pain as measured by limb use during ambulation and standing. The MIA animals showed increased thermal, but not mechanical, sensitivity compared to ACL+DMM animals. Joint degeneration was significantly more severe in the MIA model at 6 weeks. Our pilot data suggest both the ACL+DMM and MIA models are equal in terms of clinically relevant pain behaviors, but the MIA model is associated with more severe histological changes over time potentially making it more suitable for screening disease modifying agents. Future work should further characterize each model in terms of complex pain behaviors and biochemical, molecular, and imaging analysis of the sensory system and joint tissues, which will allow for more informed decisions associated with model selection and investigative outcomes.
The study of companion (pet) dogs is an area of great translational potential, as they share a risk for many conditions that afflict humans. Among these are conditions that affect sleep, including ...chronic pain and cognitive dysfunction. Significant advancements have occurred in the ability to study sleep in dogs, including development of non-invasive polysomnography; however, basic understanding of dog sleep patterns remains poorly characterized. The purpose of this study was to establish baseline sleep-wake cycle and activity patterns using actigraphy and functional linear modeling (FLM), for healthy, adult companion dogs. Forty-two dogs were enrolled and wore activity monitors for 14 days. FLM demonstrated a bimodal pattern of activity with significant effects of sex, body mass, and age; the effect of age was particularly evident during the times of peak activity. This study demonstrated that FLM can be used to describe normal sleep-wake cycles of healthy adult dogs and the effects of physiologic traits on these patterns of activity. This foundation makes it possible to characterize deviations from normal patterns, including those associated with chronic pain and cognitive dysfunction syndrome. This can improve detection of these conditions in dogs, benefitting them and their potential as models for human disease.
Nerve growth factor (NGF) is essential for the survival of sensory and sympathetic neurons during development. However, in the adult, NGF and its interaction with tropomyosin receptor kinase A ...receptor (TrkA) has been found to play a critical role in nociception and nervous system plasticity in pain conditions. Thus, various monoclonal antibody (mAb) therapies targeting this pathway have been investigated in the development of new pharmacotherapies for chronic pain. Although none of the mAbs against NGF are yet approved for use in humans, they look very promising for the effective control of pain. Recently, species-specific anti-NGF mAbs for the management of osteoarthritis (OA)-associated pain in dogs and cats has been developed, and early clinical trials have been conducted. Anti-NGF therapy looks to be both very effective and very promising as a novel therapy against chronic pain in dogs and cats. This review outlines the mechanism of action of NGF, the role of NGF in osteoarthritis, research in rodent OA models and the current status of the development of anti-NGF mAbs in humans. Furthermore, we describe and discuss the recent development of species-specific anti-NGF mAbs for the treatment of OA-associated pain in veterinary medicine.
Modern health care has brought our society innumerable benefits but has also introduced the experience of pain very early in life. For example, it is now routine care for newborns to receive various ...injections or have blood drawn within 24 h of life. For infants who are sick or premature, the pain experiences inherent in the required medical care are frequent and often severe, with neonates requiring intensive care admission encountering approximately fourteen painful procedures daily in the hospital. Given that much of the world has seen a steady increase in preterm births for the last several decades, an ever-growing number of babies experience multiple painful events before even leaving the hospital. These noxious events occur during a critical period of neurodevelopment when the nervous system is very vulnerable due to immaturity and neuroplasticity. Here, we provide a narrative review of the literature pertaining to the idea that early life pain has significant long-term effects on neurosensory, cognition, behavior, pain processing, and health outcomes that persist into childhood and even adulthood. We refer to clinical and pre-clinical studies investigating how early life pain impacts acute pain later in life, focusing on animal model correlates that have been used to better understand this relationship. Current knowledge around the proposed underlying mechanisms responsible for the long-lasting consequences of neonatal pain, its neurobiological and behavioral effects, and its influence on later pain states are discussed. We conclude by highlighting that another important consequence of early life pain may be the impact it has on later chronic pain states-an area of research that has received little attention.
Maintaining an active lifestyle is considered a hallmark of successful aging. Physical activity significantly reduces the risk of cognitive decline and Alzheimer's disease in humans. However, pain ...and lack of motivation are important barriers to exercise. Dogs are a remarkable model for translational studies in aging and cognition as they are prone to Canine Cognitive Dysfunction syndrome, which has many similarities with Alzheimer's disease. According to owner reports, changes in activity levels are characteristic of this syndrome, with decreased daytime activity, but also excessive pacing, especially at sleep time. We used physical activity monitors to record the activity of 27 senior dogs and evaluated the association between activity level and age, fractional lifespan, cognitive status measured by an owner questionnaire and cognitive tests. We also assessed the relationship between activity and joint/spinal pain, and the off/on leash gait speed ratio (a potential marker of gait speed reserve and motivation). We found that activity patterns in dogs are associated with fractional lifespan and working memory. Additionally, dogs with higher on/off leash gait speed are more active in the afternoon of weekdays. These results encourage future studies evaluating how physical activity can improve or delay cognitive impairment in senior dogs.
BackgroundFeline osteoarthritis (OA) is a common cause of long-standing pain and physical dysfunction. Performing a physical examination of a cat is often challenging. There is a need for ...disease-specific questionnaires or the so-called clinical metrology instruments (CMIs) to facilitate diagnosis and evaluation of treatment of feline OA. The CMI provides the owners an assessment of the cat’s behavioural and lifestyle changes in the home environment. The purpose of the study was to evaluate readability, internal consistency, reliability and discriminatory ability of four CMIs.MethodsThis is a prospective, cross-sectional study with 142 client-owned cats. Feline OA was diagnosed based on medical history, orthopaedic examination and radiography.ResultsThe results indicate that all four instruments have sound readability, internal consistency, are reliable over time and have good discriminatory ability. Preliminary cut-off values with optimal sensitivity and specificity were suggested for each instrument. The osteoarthritic cats showed significant changes in behavioural response to pain during orthopaedic examination, compared with sound cats.ConclusionThe results indicate that all four questionnaires make an important contribution in a clinical setting, and that the cat’s behavioural response to pain during physical examination should be a parameter to take into account as a possible indication of chronic pain.
Endogenous Pain Modulation (EPM) impairment is a significant contributor to chronic pain. Conditioned pain modulation (CPM) testing assesses EPM function. Osteoarthritic (OA) dogs are good ...translational models, but CPM has not been explored. Our aim was to assess EPM impairment in OA dogs compared to controls using CPM. We hypothesized that CPM testing would demonstrate EPM impairment in OA dogs compared to controls. Dogs with stifle/hip OA and demographically-matched controls were recruited. The pre-conditioning test stimulus, using mechanical/thermal quantitative sensory testing (MQST or TQST), were performed at the metatarsus. A 22N blunt probe (conditioning stimulus) was applied to the contralateral antebrachium for 2 minutes, followed by MQST or TQST (post-conditioning test stimulus). The threshold changes from pre to post-conditioning (∆MQST and ∆TQST) were compared between OA and control dogs. Twenty-four client-owned dogs (OA, n = 11; controls, n = 13) were recruited. The ∆MQST(p < 0.001) and ∆TQST(p < 0.001) increased in control dogs but not OA dogs (∆MQST p = 0.65; ∆TQST p = 0.76). Both ∆MQST(p < 0.001) and ∆TQST(p < 0.001) were different between the OA and control groups. These are the first data showing that EPM impairment is associated with canine OA pain. The spontaneous OA dog model may be used to test drugs that normalize EPM function.
Osteoarthritis (OA) is a chronic condition often associated with pain, affecting approximately fourteen percent of the population, and increasing in prevalence. A globally aging population have made ...treating OA-associated pain as well as maintaining mobility and activity a public health priority. OA affects all mammals, and the use of spontaneous animal models is one promising approach for improving translational pain research and the development of effective treatment strategies. Accelerometers are a common tool for collecting high-frequency activity data on animals to study the effects of treatment on pain related activity patterns. There has recently been increasing interest in their use to understand treatment effects in human pain conditions. However, activity patterns vary widely across subjects; furthermore, the effects of treatment may manifest in higher or lower activity counts or in subtler ways like changes in the frequency of certain types of activities. We use a zero inflated Poisson hidden semi-Markov model to characterize activity patterns and subsequently derive estimators of the treatment effect in terms of changes in activity levels or frequency of activity type. We demonstrate the application of our model, and its advance over traditional analysis methods, using data from a naturally occurring feline OA-associated pain model.
The center of mass (CoM) is the location in a body where mass distribution is balanced. It has a fundamental role in balance and motion which has been poorly described in the dog. The objective of ...this study was to estimate the variance of the center of mass (CoM) in a heterogeneous population of client-owned dogs and to describe the relationship between CoM, subject morphometrics and an inertial measurement unit (IMU) box positioned ventrally on a neck collar. A single force platform and a reaction board were used to determine CoM in the transverse, sagittal and dorsal planes in thirty-one healthy adult dogs. A series of morphometric measurements were acquired with each dog standing, including distances relative to an IMU box positioned ventrally on a neck collar. Mean transverse plane CoM was 48% the distance from ischium to the IMU box, near the xiphoid process. Mean sagittal place CoM was 59% the width of the chest on the left side. Mean dorsal plane CoM was 41% the distance from the most dorsal to the most ventral aspect of the body. Dog length was the primary variable required to maximize the relationship between three-dimensional CoM and identifiable variables measured. A CoM based normalization procedure should be considered to normalize mass or motion based outcome measure output (e.g., ground reaction forces, vector acceleration) in a heterogeneous population of dogs. Future research will be needed to determine if CoM-based normalization procedures reduce variance in outcome measures affected by subject morphometrics.
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