Translational animal models using veterinary patients – An example of canine osteoarthritis (OA)

2012 ◽  
Vol 3 (2) ◽  
pp. 84-89 ◽  
Author(s):  
Outi Vainio

AbstractBackground and purposeThe use of laboratory animals in pain research has powerfully contributed to our detailed understanding of the physiological mechanisms of pain. Animal models also represent an essential tool to screen and select novel drug molecules with potentially analgesic properties. Despite of the inevitable input of laboratory animal trials, recent studies have shown that animal pain models have repeatedly failed to predict clinical analgesic efficacy and adverse side effects of potential drug molecules in human pain patients. This paper provides a review of the laboratory animal models of OA, which have been developed to test efficacy of novel analgesics. The paper also presents spontaneous OA in canine veterinary patients, and methods to observe chronic pain in nonverbal dogs.MethodsPubMed data base was searched as a reference list to locate most relevant articles. A number of 118 articles including 4 reviews were located. Web pages of 4 establishments and 2 private organizations were also accessed.ResultsThe clinical expression and pathogenesis of naturally occurring OA in dogs is considered an analogous disease that occurs in humans, including pain and lameness. OA may occur in any joint in dogs as well as in humans. Primary idiopathic OA in dogs is rare, but certain breeds may be predisposed to it. For the most part, canine OA is considered secondary to acquired or congenital musculoskeletal disorders. Concomitant factors, such as aging and obesity, likely accelerate progression. However, mechanical factors appear to predominate in the etiopathogenesis of canine spontaneous OA. Both subjective (validated questionnaire) and objective (gait analysis) tools are available to measure OA related pain in dogs. Information on the prevalence of canine OA is limited, but rough surveys suggest that 11 million dogs in the United States and 5 million in Europe could suffer from OA. Ethical considerations concerning the use of privately owned dogs can be resolved by a careful experimental design.ConclusionCanine spontaneous OA could serve as a translational animal model that would more closely mimick clinical OA related pain conditions in humans. Privately owned dogs would make a solution to fix the gap between animal pain models and clinical trials when testing potential analgesic drug molecules. Close interdisciplinary cooperation would guarantee that both scientific and ethical intentions would be achieved.ImplicationsThe predictability of translational pain research would improve by using privately owned dogs as chronic pain models when testing novel analgesics.

2017 ◽  
Vol 16 (1) ◽  
pp. 187-187
Author(s):  
S. Hestehave ◽  
G. Munro ◽  
T. Brønnum-Pedersen ◽  
A.M. Heegaard ◽  
K.S.P. Abelson

Abstract Aims Translating preclinical drug-efficacy of analgesics from animal models to humans has proven challenging with many failures. Reasons are likely multifaceted, but lack of sufficiently rigorous study design, and phenotypical relevant animal models may be part of the explanation. Chronic pain is often associated with substantial comorbid burden, consisting of changes in affective state and cognitive impairment amongst other behavioral disturbances. Accordingly, many preclinical pain research activities have started to include assessment of comorbidity as a possible experimental outcome measure, but surprisingly, little consideration has been paid to the influence of animal-related factors to pain models. To address this essential issue, we have embarked on several comparative experiments in different pain-models, comparing Sprague Dawley’s (SD) from two different vendors with different inbred rat strains (Lewis (LEW), Fisher (F344) and Wistar Kyoto (WKY)) selected based on reported stress, depression, inflammatory and pain phenotypes. Methods Male rats were characterized in acute (hot-plate), inflammatory (Complete Freund’s Adjuvant (CFA)) and neuropathic (Spared Nerve Injury (SNI)) pain models, with dose-response to morphine (0.3–6.0 mg/kg) in hot-plate, CFA-induced hyperalgesia, and a locomotor motility-assay (LMA). Results F344 and SD’s were sensitive to morphine in hotplate and CFA (Minimum Effective Dose (MED) = 3.0 mg/kg). WKY rats developed a less robust mechanical hypersensitivity after CFA injection, and were less sensitive to morphine in both pain-tests (MED = 6.0 mg/kg). LEW rats were completely insensitive to morphine in the hot plate, in contrast to reversal of CFA-induced hyperalgesia (MED = 3.0 mg/kg). Additionally, neuropathic sensitivity developed with a later onset and less robustly in this strain after SNI. All strains tested in LMA exhibited sedative effects at 3.0 mg/kg. Conclusions Sensory phenotyping in response to acute, inflammatory and neuropathic pain, and sensitivity to morphine in these strains indicates that different pathophysiological mechanisms are engaged after injury. This could have profound implications for translating preclinical drug discovery efforts into pain-patients.


2021 ◽  
Author(s):  
Joseph M. Williams ◽  
Courtney A. Kelley ◽  
Ricardo Vallejo ◽  
David C. Platt ◽  
David L. Cedeño

Spinal cord stimulation (SCS) is an electrical neuromodulation technique with proven effectiveness and safety for the treatment of intractable chronic pain in humans. Despite its widespread use, the mechanism of action is not fully understood. Animal models of chronic pain, particularly rodent-based, have been adapted to study the effect of SCS on pain-like behavior, as well as on the electrophysiology and molecular biology of neural tissues. This chapter reviews animal pain models for SCS, emphasizing on findings relevant to advancing our understanding of the mechanism of action of SCS, and highlighting the contribution of the animal model to advance clinical outcomes. The models described include those in which SCS has been coupled to neuropathic pain models in rats and sheep based on peripheral nerve injuries, including the chronic constriction injury (CCI) model and the spared nerve injury model (SNI). Other neuropathic pain models described are the spinal nerve ligation (SNL) for neuropathic pain of segmental origin, as well as the chemotherapy-induced and diabetes-induced peripheral neuropathy models. We also describe the use of SCS with inflammatory pain and ischemic pain models.


1997 ◽  
Vol 20 (3) ◽  
pp. 458-459 ◽  
Author(s):  
Paolo Marchettini ◽  
Marco Lacerenza ◽  
Fabio Formaglio

The central hyperexcitability observed in animal models supports a pathophysiological explanation for chronic human pain. Novel information on cholecystokinin (CCK) upregulation offers a rationale for reduced opioid response in neuropathic pain. However, the basic information provided by scientists should not lead clinicians to equate experimental models to chronic human conditions. Clinicians should provide careful reports and attempt to classify pathophysiologically clinical conditions that have so far been grouped generically. [blumberg et al.; coderre & katz; dickenson; wiesenfeld-hallin et al.]


2018 ◽  
Author(s):  
B. Monteiro ◽  
M. Moreau ◽  
C. Otis ◽  
L. De Lorimier ◽  
J. Pelletier ◽  
...  

2019 ◽  
Vol 14 (8) ◽  
pp. 644-653 ◽  
Author(s):  
Jinxuan Ren ◽  
Na Liu ◽  
Na Sun ◽  
Kehan Zhang ◽  
Lina Yu

Chronic pain is a common condition that seriously affects the quality of human life with variable etiology and complicated symptoms; people who suffer from chronic pain may experience anxiety, depression, insomnia, and other harmful emotions. Currently, chronic pain treatments are nonsteroidal anti-inflammatory drugs and opioids; these drugs are demonstrated to be insufficient and cause severe side effects. Therefore, research into new therapeutic strategies for chronic pain is a top priority. In recent years, stem cell transplantation has been demonstrated to be a potent alternative for the treatment of chronic pain. Mesenchymal stem cells (MSCs), a type of pluripotent stem cell, exhibit multi-directional differentiation, promotion of stem cell implantation, and immune regulation; they have also been shown to exert analgesic effects in several chronic pain models. Exosomes produced by MSCs have been demonstrated to relieve painful symptoms with fewer side effects. In this review, we summarize the therapeutic use of MSCs in various chronic pain studies. We also discuss ways to enhance the treatment effect of MSCs. We predict in the future, cell-free therapies for chronic pain will develop from exosomes secreted by MSCs.


Author(s):  
Scott Lehmann

In the United States, private ownership of land is not a new idea, yet the federal government retains title to roughly a quarter of the nation's land, including national parks, forests, and wildlife refuges. Managing these properties is expensive and contentious, and few management decisions escape criticism. Some observers, however, argue that such criticism is largely misdirected. The fundamental problem, in their view, is collective ownership and its solution is privatization. A free market, they claim, directs privately owned resources to their most productive uses, and privatizing public lands would create a free market in their services. This timely study critically examines these issues, arguing that there is no sense of "productivity" for which it is true that greater productivity is both desirable and a likely consequence of privatizing public lands or "marketizing" their management. Lehmann's discussion is self-contained, with background chapters on federal lands and management agencies, economics, and ethics, and will interest philosophers as well as public policy analysts.


2012 ◽  
Vol 2 (3) ◽  
pp. 295-303 ◽  
Author(s):  
Gordon JG Asmundson ◽  
Holly A Parkerson ◽  
Mark Petter ◽  
Melanie Noel

2021 ◽  
pp. 1-23
Author(s):  
Ömer Elma ◽  
Elien Lebuf ◽  
Arturo Quiroz Marnef ◽  
Sevilay Tümkaya Yilmaz ◽  
Iris Coppieters ◽  
...  

Pain Medicine ◽  
2020 ◽  
Author(s):  
Mary E Morales ◽  
R Jason Yong

Abstract Objective To summarize the current literature on disparities in the treatment of chronic pain. Methods We focused on studies conducted in the United States and published from 2000 and onward. Studies of cross-sectional, longitudinal, and interventional designs were included. Results A review of the current literature revealed that an adverse association between non-White race and treatment of chronic pain is well supported. Studies have also shown that racial differences exist in the long-term monitoring for opioid misuse among patients suffering from chronic pain. In addition, a patient’s sociodemographic profile appears to influence the relationship between chronic pain and quality of life. Results from interventional studies were mixed. Conclusions Disparities exist within the treatment of chronic pain. Currently, it is unclear how to best combat these disparities. Further work is needed to understand why disparities exist and to identify points in patients’ treatment when they are most vulnerable to unequal care. Such work will help guide the development and implementation of effective interventions.


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