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ADVANCED DYNAMIC WEIGHT BEARING
(Model: BIO-DWB-AUTO-M - For mice)
The advanced version of our Dynamic Weight Bearing Test allows for faster paw identification, based on a video solution taking advantage of the most advanced algorithms of morphologic analysis in dynamic conditions. An efficient and advanced alternative to traditional incapacitance tests for assessing pain sensitivity in your research on analgesia/nociception involving rats and mice, including work on ostheoarthritis, bone cancer, analgesic substances, Parkinson disease, allodynia...

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  • LAB RESEARCH Miami, Etats-Unis
  • NEUROFITS Illkirch,France
  • ANS BIOTECH Clermont-Ferrand,France
  • ARMY RESEARCH CENTER France
  • CNRS Marseille,France
  • CNRS Strasbourg, France
  • AMGEN Thousand Oaks, USA
  • MC MASTER UNIVERSITY Hamilton, Canada
  • UNIVERSITE DE SHERBROOKE Sherbrooke, Canada
  • INSTITUTE OF PHARMACOLOGY KRAKOVIA, Poland
  • UNIVERSITY OF SAO PAULO PHARMACOLOGY SAO PAULO, Brazil
  • THE UNIVERSITY OF NEWCASTLE CALLAGHAN, Australia
  • UNIVERSITY OF GALSGOW SCOTLAND, UK
  • UNIVERSITY OF MARYLAND BALTIMORE, USA
  • INSERM Paris,France
  • INSERM Clermont-Ferrand,France
  • ISERM Bordeaux,France
  • PHILIPS REASERCH Einvoden, Netherlands
  • SANOFI-AVENTIS Montpellier, France
  • BAYER Berlin, Germany
  • GRUNENTHAL Aachen, Germany
  • CHARLES RIVER Montréal, Canada
  • ABBOTT Waukegan, USA
  • HARVARD MEDICAL SCHOOL Boston,USA
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! NEW RESEARCH WORK ! A recent publication by C. Pitzer, R. Kuner, A. Tappe-Theodor in "Molecular Pain" highlights the merits of using Bioseb's Advanced Dynamic Weight Bearing: Voluntary and evoked behavioral correlates in neuropathic pain states under different social housing conditions

Voluntary and evoked behavioral correlates in neuropathic pain states under different social housing conditions
C. Pitzer, R. Kuner, A. Tappe-Theodor
University of Heidelberg
Published in "Molecular Pain" (2017-06-15)


BACKGROUND
There is an urgent need to develop and incorporate novel behavioral tests in classically used preclinical pain models. Most rodent studies are based upon stimulus-evoked hindpaw measurements even though chronic pain is usually a day and night experience. Chronic pain is indeed a debilitating condition that influences the sociability and the ability for voluntary tasks, but the relevant behavioral readouts for these aspects are mostly under-represented in the literature. Moreover, we lack standardization in most behavioral paradigms to guarantee reproducibility and ensure adequate discussion between different studies. This concerns not only the combination, application, and duration of particular behavioral tasks but also the effects of different housing conditions implicating social isolation.

RESULTS
Our aim was to thoroughly characterize the classically used spared nerve injury model for 12 weeks following surgery. We used a portfolio of classical stimulus-evoked response measurements, detailed gait analysis with two different measuring systems (Dynamic weight bearing (DWB) system and CatWalk), as well as observer-independent voluntary wheel running and home cage monitoring (Laboras system). Additionally, we analyzed the effects of social isolation in all behavioral tasks. We found that evoked hypersensitivity temporally matched changes in static gait parameters, whereas some dynamic gait parameters were changed in a time-dependent manner. Interestingly, voluntary wheel running behavior was not affected in spared nerve injury mice but by social isolation. Besides a reduced climbing activity, spared nerve injury mice did not showed tremendous alterations in the home cage activity.

CONCLUSION
This is the first longitudinal study providing detailed insights into various voluntary behavioral parameters related to pain and highlights the importance of social environment on spontaneous non-evoked behaviors in a mouse model of chronic neuropathy. Our results provide fundamental considerations for future experimental planning and discussion of pain-related behavioral changes.
Summary

2006 - Incapacitance test, or Static Weight Bearing: used in nociceptive and analgesia research for assessing pain sensitivity in rodents.
2008 - Dynamic Weight Bearing Test: operator-independent, time-saving, convenient for large amounts of rodents, no animal stress.
2011 - Advanced Dynamic Weight Bearing Test: fast, semi-automatic, operator-independent with advanced video-based software.

Presentation & History

Advanced Dynamic Weight Bearing - Detail with mouse
Advanced Dynamic Weight Bearing
Detail with mouse
Bioseb's Advanced Dynamic Weight Bearing Test is the result of years of R&D based on the principles of early incapacitance instruments, which we evolved into Static Weight Bearing and Dynamic Weight Bearing apparatus, before releasing the brand new Advanced Dynamic Weight Bearing instrument.

Weight Bearing of rodents, also named « incapacitance » test, is well known in nociceptive and analgesia research works, and used for studying ostheoarthritis, bone cancer, nerve injuries, analgesic substances, Parkinson, allodynia, etc. Traditional « static » type instruments have been used in the last years for assessing pain sensitivity in rodents (mice and rats).

Those static incapacitance instruments, although showing well correlated results vs. paw pressure vocalization test, calibrated Von Frey filaments, etc. (cf Richebe P, Laulin JP, Simonnet G, Anesthesiology 2005, Pain 2007,...), are highly dependant on the animal's (rat or mouse) position inside a stressful restrainer. This makes these systems time-consuming and difficult to use, particularly when large number of rodents are considered.

In 2008 Bioseb presented the Dynamic Weight Bearing - New Incapacitance Test, a new test for assessing spontaneous pain in freely moving rodents, which is based on an instrumented-floor cage and a combined video acquisition system. The Dynamic Weight Bearing test, especially suitable for research on Parkinson and allodynia, was a major break-through in the field of research on analgesia: operator-independent, time-saving, convenient for manipulating large amounts of rodents, and induces no stress on the animal (rat or mouse).

The system has been used extensively by many customers from private firms to academic labs since 2008 for various types of research on analgesia and nociception.

The result of this “live” experiment is summarised in a recent publication in Physiology & Behavior from the team of Dr Sarret Sherbrooke (Canada) and shows that usual ipsilateral/contralateral hindpaw weight ratio measurements overestimate the effect of an analgesic drug. The Dynamic Weight Bearing test, which calculates the percentage of weight borne by each paw compared to the total body weight while the animal is able to move freely, offers results that are much closer to reality. The study performed with mice and rats on three models of pain (inflammatory, cancer, neuropathic) reveals that the forepaw compensation is an important indication in the load pattern redistribution.

The Dynamic Weight Bearing system also offers the possibility of conducting the experiment over a longer observational period (5 minutes) without an operator (thus reducing stress on the animal), and without any habituation period. With these exclusive features, the DWB opens a new and improved generation of instruments for drugs screening and optimization of preclinical models.

The latest version is now a semi-automatic, operator-independent instrument.

Screenshot of Bioseb's new Advanced Dynamic Weight Bearing Software
Advanced Dynamic Weight Bearing
Screenshot of Bioseb's Software
Operating principle

Performing the same measurements as the original manual Version, the Advanced DWB (Dynamic Weight Bearing) improves two of the turnkey points of the system: the speed of operation and the operator independent factor. The Advanced DWB allows the user to reduce the most important phase of the process by a factor of 8 to 10, thus the analysis of 1 animal will take 1 to 2 minutes and be operator-independent.

The results encompass a lot of valuable information but will ask for a minimum of manpower and many more animal analysis can be done in the same amount of time than with a manual instrument. The software gives the weight distribution of the animal (rat or mouse), per limb, with additional ratio computations and filtering options.

Analysis and replay can be performed on site or remotely using Bioseb's exclusive software for Dynamic Weight Bearing and Incapacitance tests. During the analysis and replay, the operator can check and secure each limb recognition for hind and front paws. The weight distribution of the animal (rat or mouse) per limb is then shown in the result window, for each time period with the mean and the variation coefficient.

Parameters measured

• Weight for each paw (g and % total animal weight)
• Weight for grouped front and rear paws (g and %total animal weight)
• Left/Right and Front/Rear weight ratio
• Surface for each paw (mm²)
• Surface for grouped front and rear paws (mm²)
• Variability (standart deviation/mean) for each parameter
• Parameters are given for each posture and as a mean for the whole experiment
• Duration of different postures (4 paws, rearing…) over the whole experiment (s)
• Total time spent on each paw over the whole experiment (s)


Key features

Advantages of Bioseb’s dynamic weight bearing system over static incapacitance systems
• Operator-independent
• Time-saving
• Convenient for manipulating large amounts of rodents
• No stress induced on the animal (rat or mouse)

The new version of our Dynamic Weight Bearing Apparatus offers ground-breaking new functionalities:
• Experiment management: define experiment parameters, import a list of subjects and run the total experience. View and analyze subjects on an individual or group basis.
• Possibility to run longer experiments
• Record up to 30 measurements per second (better accuracy on animal positioning)
• Perform detailed analysis on immobility, mobility, or both conditions
• Improved scoring algorithm detecting 80% of the paws
• Special tool to validate video parameters
• Improved tools for scoring, undo/redo option, fusion , etc
• Coming soon: special model for guinea pigs

Applications for your research

Pain - Nociception/Analgesia
• Bone cancer models
• Neuropathic models
• Inflammation model
• Post surgery models
• Osteo-arthrisis models
• Arthrose models

Physiology
• Peripheric ischemia
• Cerebrovascular accident models

Neurology
• Spinal cord injuries recovery process

Other research applications
• Calcaneal tendon disease
• Crucial ligaments disease

Versions and setup

All current users of the standard version of Bioseb's Dynamic Weight Bearing are eligible to receive the upgrade which is composed of a software, a high resolution USB camera and a specially designed cover.

The instrument and its camera do not require special lighting conditions : day light conditions. Direct close illumination may be avoided.

The basal feature remains accessible from the new version if necessary especially to train new lab users previous to switch to the semi-automated analysis or simply to validate the results.

The ADVANCED DWB is available in three setups RAT (BIO-DWB-AUTO-R), MICE (BIO-DWB-AUTO-M), COMBINED RAT MICE (BIO-DWB-AUTO-DU).
New Advanced Weight Bearing System for Mouse and Rat, by Bioseb: camera, cover, cage and animal
New Advanced Weight Bearing System for Mouse and Rat, by Bioseb: camera, cover, cage and animal

Publications (Click on an article to show details and read the abstract)

PAIN
- Mechanical allodynia & hyperlagesia -
Comparison of evoked and non-evoked endpoints in a rodent pain model and potential relevance to non-evoked human pain. (2012)
Comparison of evoked and non-evoked endpoints in a rodent pain model and potential relevance to non-evoked human pain.
D. L. Li, M.P. Johnson, J.D. Kennedy et al.
Eli Lilly and Co., Indianapolis, USA
Published in "Society for Neuroscience 2012" (2012-10-15)

The translational value of currently utilized animal pain models has been frequently debated ever since the clinical failure of the NK-1 antagonists. While there are a number of reasons underlying failed clinical trials, a concern often noted is that evoked endpoints in rodent pain models do not accurately reflect on-going (non-evoked) pain as is most often reported in the clinic. Here we compare standard evoked endpoint measurements, including thermal hyperalgesia (Hargreaves test) and mechanical hypersensitivity (Randall-Selitto test) to dynamic weight bearing using the BIOSEB automated system in the context of the Carrageenan model of acute inflammation. Dynamic weight bearing averages a series of measures over time, eliminating potential subjectivity associated with standard static weight bearing/incapacitance testing. Since this test does not involve a noxious stimulus, changes in the weight animals place on the injured paw may reflect the level of on-going pain. NSAIDs are standard-of-care drugs for mild/moderate inflammatory pain and as well are effective in reversing evoked pain endpoints in the Carrageenan model. Drug doses less than the minimally efficacy doses (MED) for reversing evoked thermal or mechanical hypersensitivity were able to reverse Carrageenan-induced weight bearing deficits. These doses/systemic exposure more closely match effective doses/systemic exposures used in the treatment of human inflammatory pain. The use of non-evoked pain model endpoints such as dynamic weight bearing can provide a valuable means for evaluating on-going pain as part of a comprehensive behavioral pain model screening paradigm.

Polyamine deficient diet to relieve pain hypersensitivity. (2008)
Polyamine deficient diet to relieve pain hypersensitivity.
C. Rivat, P. Richebé, E. Laboureyras, J.-P. Laulin, R. Havouis et al.
UMR CNRS 5227, “Mouvement-Adaptation-Cognition”, Team “Homéostasie-Allostasie-Pathologie-Réhabilitation”, Bordeaux, France.
Published in "Pain" (2008-06-30)

There is a compelling body of evidence that N-methyl-d-aspartate receptors (NMDA-R) play a critical role in the development and maintenance of pain hypersensitivity. However, long-term treatments with NMDA-R antagonists are limited by unacceptable side effects. Since polyamines modulate the functioning of NMDA-R and mainly originate from normal dietary intake and bacterial metabolism in the gut, we developed a nutritional therapy based on dietary polyamine deficiency. Here, we reported that a polyamine deficient diet (PD diet) for 7 days prevented the enhancement of tyrosine phosphorylation of the spinal NR2B subunit-containing NMDA-R associated with inflammation in rats. Based on these data, we studied the ability of PD diet to prevent long-lasting pain hypersensitivity associated with tissue injury on one hind paw by evaluating long-lasting changes in both mechanical nociceptive threshold and weight bearing. A PD diet strongly reduced long-lasting hyperalgesia induced by inflammation or incision, especially in fentanyl-treated rats. Moreover a PD diet also prevented the exaggerated hyperalgesia induced by a second inflammation performed 7 days after the first one. A PD diet also opposed paradoxical hyperalgesia induced by non-nociceptive environmental stress in rats with pain and opioid experiences. A PD diet reversed pain hypersensitivity associated with monoarthritis or neuropathy and restored the analgesic effect of morphine. Since PD diet was devoid of any noticeable side effects, this nutritional therapy could be part of an effective and safe strategy for pre-emptive analgesia and for reducing the transition from acute to chronic pain and its outcomes in various pain syndromes.

- Inflammatory pain -
The Effects of Endocannabinoid Modulation and Neurogenic Inflammation in Experimental Knee Joint Arthritis (2015)
The Effects of Endocannabinoid Modulation and Neurogenic Inflammation in Experimental Knee Joint Arthritis
Krustev, Eugene
Dalhousie University Halifax, Nova Scotia
Published in "Faculty of Graduate Studies Online Theses" (2015-07-31)

Arthritis is a debilitating condition, and a leading cause of disability worldwide. Despite the prevalence of arthritis, few therapies are satisfactorily efficacious, and many are limited by serious adverse effects. It is for these reasons that the development of newer, safer and more efficacious arthritis therapies is essential. The knee is the second largest joint in the human body, and is one of the most affected joints in osteoarthritis. Furthermore, the knee is easily accessible in mice, making it an ideal joint for inducing experimental arthritis in rodents. Local neurogenic inflammation is mediated by the release of neuropeptides from the peripheral terminals of nociceptive fibres. Neurogenic inflammation has been implicated in a number of inflammatory conditions, including arthritis; therefore, understanding how neurogenic inflammation contributes to joint inflammation may help in the development of novel arthritis therapeutics. One family of molecules that shows tremendous promise for the management of arthritic inflammation and pain are the cannabinoids. These compounds were first identified in the Cannabis plant, but subsequent research has identified an endogenous cannabinoid system, that plays a role in both health and disease. One method that is used to increase endocannabinoid activity is inhibiting the enzymes responsible for their degradation. Using a drug called URB597, we can block fatty acid amide hydrolase, increasing articular endocannabinoids. The aim of this thesis was to investigate the contribution of neurogenic inflammation in experimental knee joint disease, as well as the therapeutic potential of the endocannabinoid system in joint inflammation and the development of arthritic pain.

Reduction of Neuropathic and Inflammatory Pain through Inhibition of the Tetrahydrobiopterin Pathway (2015)
Reduction of Neuropathic and Inflammatory Pain through Inhibition of the Tetrahydrobiopterin Pathway
Latremoliere A, Latini A, Andrews N, Cronin SJ et al.
Kirby Neurobiology Center, Boston Children's Hospital and Department of Neurobiology, Harvard Medical School, Boston, USA.
Published in "Neuron." (2015-06-17)

Human genetic studies have revealed an association between GTP cyclohydrolase 1 polymorphisms, which decrease tetrahydrobiopterin (BH4) levels, and reduced pain in patients. We now show that excessive BH4 is produced in mice by both axotomized sensory neurons and macrophages infiltrating damaged nerves and inflamed tissue. Constitutive BH4 overproduction in sensory neurons increases pain sensitivity, whereas blocking BH4 production only in these cells reduces nerve injury-induced hypersensitivity without affecting nociceptive pain. To minimize risk of side effects, we targeted sepiapterin reductase (SPR), whose blockade allows minimal BH4 production through the BH4 salvage pathways. Using a structure-based design, we developed a potent SPR inhibitor and show that it reduces pain hypersensitivity effectively with a concomitant decrease in BH4 levels in target tissues, acting both on sensory neurons and macrophages, with no development of tolerance or adverse effects. Finally, we demonstrate that sepiapterin accumulation is a sensitive biomarker for SPR inhibition in vivo.

Evaluation of Dynamic Weight Bearing for Measuring Nonevoked Inflammatory Hyperalgesia in Mice (2015)
Evaluation of Dynamic Weight Bearing for Measuring Nonevoked Inflammatory Hyperalgesia in Mice
Griffioen, Mari A.; Dernetz, Valerie H.; Yang, Gee Su; Griffith, Kathleen A.; Dorsey, Susan G.; Renn, Cynthia L.
Department of Pain & Translational Symptom Science, School of Nursing, University of Maryland, Baltimore
Published in "Nursing Research" (2015-04-01)

Background: Animal models in pain research have suggested that inclusion of both evoked and nonevoked behavioral measures is needed to better reflect the human pain experience. Individuals with chronic pain are known to experience spontaneous pain, in addition to pain after exposure to an external stimulus. Recently, the dynamic weight bearing (DWB) apparatus was developed to assess for nonevoked hyperalgesia by capturing weight bearing and surface distribution in the paws of mice after acute inflammation.

Objectives: The aim of this study was to evaluate the DWB test as a measure of nonevoked hyperalgesia.

Methods: The experimental group received an intraplantar injection in the left hind paw of the inflammatory agent—complete Freund’s adjuvant (CFA)—whereas the vehicle control group received a saline injection and the naive control group had no treatment. Calipers and a plethysmometer were used to verify inflammation and the hot-plate test was used as a measure for stimulus-evoked hyperalgesia. Data were collected at baseline; 3 hours; and 1, 3, and 7 days after injection.

Results: Mice injected with CFA showed a statistically significant higher mean paw thickness and volume displacement compared with the vehicle and naive control groups. In the hot-plate testing, CFA-treated mice showed lower response temperature at 7 days compared with the other groups. On the DWB test, CFA-treated mice showed a reduction in the ipsilateral paw load and surface area compared with the contralateral paw load at Days 1, 3, and 7.

Discussion: Mice with inflammation showed alterations in weight bearing as well as increased thermal hyperalgesia in comparison with control groups. These findings support the use of the DWB test as a tool for measuring nonevoked inflammatory hyperalgesia in a mouse model.

Use of dynamic weight bearing as a novel end-point for the assessment of Freund's Complete Adjuvant induced hypersensitivity in mice (2012)
Use of dynamic weight bearing as a novel end-point for the assessment of Freund's Complete Adjuvant induced hypersensitivity in mice
Ian Robinson, Becky Sargent, Jon P. Hatcher
MedImmune Ltd., Granta Park, Cambridge CB21 6GH, UK
Published in "Neuroscience Letters, Volume 524, Issue 2, Pages 107–110" (2012-08-30)

Abstract

Animal models are an integral part of pain research. However, current models tend to rely on evoked responses and there is a belief that non-evoked responses may be a more relevant behavioural readout as the animal responds in a more natural manner. Here, dynamic weight bearing (DWB), a novel method for assessing mechanical hypersensitivity, was evaluated using the Freund's Complete Adjuvant (FCA) model of inflammatory pain in mice. DWB enables the measurement of weight placed through all four paws of a freely moving animal. The data obtained from DWB was compared with data acquired using the standard static weight bearing (incapacitance) test. In both tests reversal of FCA induced mechanical hypersensitivity was investigated using the selective COX2 inhibitor celecoxib. Mice treated with FCA placed less weight through the ipsilateral hindpaw compared to vehicle controls. This reduction was reversed by celecoxib (30 mg/kg p.o.) in the dynamic and static weight bearing tests. The data presented here suggests that dynamic weight bearing may provide a novel end point for the development of new analgesics.

Highlights

? We compare the incapacitance tester with dynamic weight bearing in mice.
? Both models detect significant mechanical hypersensitivity following intraplantar FCA.
? Both models detected a reversal of mechanical hypersensitivity following oral celecoxib dosing.
? Dynamic weight bearing may be a more relevant method for assessing pain in mice.

Keywords

Inflammatory pain; Freund's Complete Adjuvant; Weight bearing; Celecoxib



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Pc requirement Windows Seven os CORE I3 or I5 processor with a minimum of 3 Go of RAM
Camera we provide a 640x 480 usb based camera high resolution delivered with its lens, the camera is fixed on the cover - when the settings are correct no need to adjust between animals
Versions available 3 versions: rat, mouse, combined rat+mouse

Model:
BIO-DWB-AUTO-M
Advanced Dynamic Weight Bearing (Modif.)
For mice Contact us

Related products:
BIO-DWB-AUTO-R
For rats Contact us
BIO-DWB-AUTO-DU
Dual: for rats and mice Contact us
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