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ELECTRONIC VON FREY 5 WITH EMBEDDED CAMERA
(Model: BIO-EVF5 - With embedded camera - for rats and mice)
The latest evolution of Bioseb's Electronic Von Frey instrument for determining the mechanical sensitivity threshold in rodents (rats and mice).

The EVF5 includes an embedded camera inside the stimulator handle and a new, dedicated software revolutionizing the experimental process.


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! NEW RESEARCH WORK ! A recent publication by D Romeo-Guitart, C Casas in "Cells" highlights the merits of using Bioseb's Electronic Von Frey 5 with embedded camera: NeuroHeal Treatment Alleviates Neuropathic Pain and Enhances Sensory Axon Regeneration

NeuroHeal Treatment Alleviates Neuropathic Pain and Enhances Sensory Axon Regeneration
D Romeo-Guitart, C Casas

Published in "Cells" (2020-03-27)


Peripheral nerve injury (PNI) leads to the loss of motor, sensory, and autonomic functions, and often triggers neuropathic pain. During the last years, many efforts have focused on finding new therapies to increase axonal regeneration or to alleviate painful conditions. Still only a few of them have targeted both phenomena. Incipient or aberrant sensory axon regeneration is related to abnormal unpleasant sensations, such as hyperalgesia or allodynia. We recently have discovered NeuroHeal, a combination of two repurposed drugs; Acamprosate and Ribavirin. NeuroHeal is a neuroprotective agent that also enhances motor axon regeneration after PNI. In this work, we investigated its effect on sensory fiber regeneration and PNI-induced painful sensations in a rat model of spare nerve injury and nerve crush. The follow up of the animals showed that NeuroHeal treatment reduced the signs of neuropathic pain in both models. Besides, the treatment favored sensory axon regeneration, as observed in dorsal root ganglion explants. Mechanistically, the effects observed in vivo may improve the resolution of cell-protective autophagy. Additionally, NeuroHeal treatment modulated the P2X4-BDNF-KCC2 axis, which is an essential driver of neuropathic pain. These data open a new therapeutic avenue based on autophagic modulation to foster endogenous regenerative mechanisms and reduce the appearance of neuropathic pain in PNI.
Presentation

New EVF (Electronic Von Frey) software with embedded video
New EVF Software with embedded video
16 years after the creation of our first Electronic Von Frey instrument, Bioseb is revolutionizing this standard test for determining the mechanical sensitivity threshold in rodents (rats and mice).

A well-known issue with classical Electronic Von Frey instruments is the necessity for the operator to bend into an uncomfortable posture in order to stimulate under the rodents' paws. Despite using more ergonomic workplace configurations (lower seats and elevated desks), the operation can remain strenuous or even painful for the operator when repeated over large cohorts of animals.

In order to solve this issue, we embedded a camera inside the stimulator handle, which allows you to record and display video directly from underneath the paws. In conjunction with our dedicated software, this innovation allowed us to re-think the position of the operator during the test.

When used on a tablet or touch-screen, the EVF5 software allows operators to visualize the video stream in real time without having to bend over. Furthermore, it integrates all additional functionalities that might be required during such a test:
• Animal lists management.
• Real-time curves display: visualizing the force over time helps operators improve their execution and the repeatability of their measurement
• A table allowing you to assign each measurement to the corresponding paw by directly clicking on the touch screen.
• A replay function for both videos and force curves allowing the operators to delete invalid measurements.
• Exporting results to an Excel spreadsheet.

Operating principles

Built around a stimulator handle connected to a touchscreen tablet with an embedded, dedicated software, the instrument was designed to offer operators a complete working environment for the Von Frey Test which does not require them to bend over during stimulation.

The operator creates a new experiment on the dedicated software and configures their animal list as well as the different paws that they wish to stimulate (usually the hind paws). The test is then started by taking the stimulator handle and observing the target zones under the animal's paw directly via the video stream on the touchscreen tablet, without having to bend over to look under the plantar surface.

Stimulation is usually applied on the rodent's hind paws. The paw's withdrawal following the mechanical stimulation is recorded as a response to the stimulus. During measurement, the operator can observe in real-time and thus adapt the intensity of the applied force.

The maximum force applied with the instrument, which corresponds to the necessary value for the paw's withdrawal, is saved into the system. The operator can then decide to validate the measured value with a simple click on the touchscreen (see screenshot below) or re-launch the measurement with a new stimulation.

New functionalities

Screen of an Electronic Von Frey
Stats screen
• Integrated video ! On the EVF5 model, the paw and plantar surface can now be visualized in a high-definition video on the screen of a touchscreen or computer. This method is not only more accurate, it is also much more comfortable for the operator.
• New software: specially designed for touchscreen tablets and offering animal lists management, real-time display of force curves over time, validation of results...
• A lighter stimulator handle with the center of gravity placed more centrally for more precise movement and better control of the increase in force.
• The new force sensor is both more accurate and rigid, improving reproducibility from amore homogenous stimulation, reproducibility. The variation linked to sudden movements is drastically reduced. The system is also easier to use on mice.
• New spring tips for mouse stimulation: by absorbing impact forces, they increase accuracy on the 0-20 grams range.

As well as all the classical functionalities that made our Electronic Von Frey a "must have" for all your research projects in analgesia and nociception:

• Large backlit LCD screen simultaneously displaying current and peak value
• Statistical functions: average value and standard deviation are computed for each subject
• Stand-alone instrument: internal memory allows the storing of up to 100 values, which may be transferred to a PC using our optional software

Dedicated software

The brand-new EVF5 software by Bioseb is built around 3 tabs for an optimal ease-of-use while offering numerous innovative functionalities:
• Video with target pointer: No more stretching or bending to target the paw. Real-time video display.
• Real-time curve display: : Immediate display of applied force helps achieve reproducible measures.
• Value assignation to each animal's paw: Special feature for touch screen PC ! Validation in 1 touch (or 1 click).

And also:
• Animal list management
• Exporting results to Microsof Excel
• Replay functionalities for both videos and force curves for accurate measurement validation

Measurement validation table with stimulated paw selection for the Bioseb Electronic Von Frey for rodents (rats and mice)
Measurement validation table with stimulated paw selection
Real-time force over time curves display for Bioseb's Electronic Von Frey
Real-time force over time curves display

Measured parameters

Electronic Von Frey is designed to:

• Measure the force applied on your subject during stimulation.
• Measures are automatically displayed in grams (g)
• You can also choose : Newton, lbs and Oz
• Measurement from 1 to 500g ! Perfect for any application !
• Quickly determine the mechanical pain sensitivity threshold !

Application domains

• Phenotyping
• Neuropathologies
• Inflammations
• Post-operative disorders
• Ghost pain
• Diabetic neuropathy
• Nerve Regeneration
Supplied with

• 1 transportation case
• 1 foot switch for hand-free resetting of the test
• 10 disposable measurement tips of 0,5 mm diameter
• 1 spring tip for thresholds of 0-10 grams

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

• PAIN •
- General pain -
• Dim light at night exposure induces cold hyperalgesia and mechanical allodynia in male mice (2020)
Dim light at night exposure induces cold hyperalgesia and mechanical allodynia in male mice
JR Bumgarner, WH Walker II, JA Liu et al
Department of Neuroscience, Rockefeller Neuroscience Institute, West Virginia University, Morgantown, WV, USA
Published in "Neuroscience" (2020-03-19)

The growing presence of artificial lighting across the globe presents a number of challenges to human and ecological health despite its societal benefits. Exposure to artificial light at night, a seemingly innocuous aspect of modern life, disrupts behavior and physiological functions. Specifically, light at night induces neuroinflammation, which is implicated in neuropathic and nociceptive pain states, including hyperalgesia and allodynia. Because of its influence on neuroinflammation, we investigated the effects of dim light at night exposure on pain responsiveness in male mice. In this study, mice exposed to four days of dim (5_lux) light at night exhibited cold hyperalgesia. Further, after 28_days of exposure, mice exhibited both cold hyperalgesia and mechanical allodynia. No heat/hot hyperalgesia was observed in this experiment. Altered nociception in mice exposed to dim light at night was concurrent with upregulated interleukin-6 and nerve growth factor mRNA expression in the medulla and elevated micro-opioid receptor mRNA expression in the periaqueductal gray region of the brain. The current results support the relationship between disrupted circadian rhythms and altered pain sensitivity. In summary, we observed that dim light at night induces cold hyperalgesia and mechanical allodynia, potentially through elevated neuroinflammation and dysregulation of the endogenous opioid system.

• In vitro and non?invasive in vivo effects of the cannabinoid?1 receptor agonist AM841 on gastrointestinal motor function in the rat (2015)
In vitro and non?invasive in vivo effects of the cannabinoid?1 receptor agonist AM841 on gastrointestinal motor function in the rat
Abalo R, Chen C, Vera G, Fichna J, Thakur GA, López-Pérez AE, Makriyannis A, Martín-Fontelles MI, Storr M
Universidad Rey Juan Carlos, Alcorcón, Madrid, Spain
Published in "Neurogastroenterol Motil." (2015-09-20)

BACKGROUND:
Cannabinoids have been traditionally used for the treatment of gastrointestinal (GI) symptoms, but the associated central effects, through cannabinoid-1 receptors (CB1R), constitute an important drawback. Our aims were to characterize the effects of the recently developed highly potent long-acting megagonist AM841 on GI motor function and to determine its central effects in rats.

METHODS:
Male Wistar rats were used for in vitro and in vivo studies. The effect of AM841 was tested on electrically induced twitch contractions of GI preparations (in vitro) and on GI motility measured radiographically after contrast administration (in vivo). Central effects of AM841 were evaluated using the cannabinoid tetrad. The non-selective cannabinoid agonist WIN 55,212-2 (WIN) was used for comparison. The CB1R (AM251) and CB2R (AM630) antagonists were used to characterize cannabinoid receptor-mediated effects of AM841.

KEY RESULTS:
AM841 dose-dependently reduced in vitro contractile activity of rat GI preparations via CB1R, but not CB2R or opioid receptors. In vivo, AM841 acutely and potently reduced gastric emptying and intestinal transit in a dose-dependent and AM251-sensitive manner. The in vivo GI effects of AM841 at 0.1 mg/kg were comparable to those induced by WIN at 5 mg/kg. However, at this dose, AM841 did not induce any sign of the cannabinoid tetrad, whereas WIN induced significant central effects.

CONCLUSIONS & INFERENCES:
The CB1R megagonist AM841 may potently depress GI motor function in the absence of central effects. This effect may be mediated peripherally and may be useful in the treatment of GI motility disorders.

• Early increasing-intensity treadmill exercise reduces neuropathic pain by preventing nociceptor collateral sprouting and disruption of chloride cotransporters homeostasis after peripheral nerve injury (2015)
Early increasing-intensity treadmill exercise reduces neuropathic pain by preventing nociceptor collateral sprouting and disruption of chloride cotransporters homeostasis after peripheral nerve injury
López-Álvarez VM, Modol L, Navarro X, Cobianchi S. et al.
Universitat Autònoma de Barcelona, and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Bellaterra, Spain
Published in "Pain" (2015-09-01)

Activity treatments, such as treadmill exercise, are used to improve functional recovery after nerve injury, parallel to an increase in neurotrophin levels. However, despite their role in neuronal survival and regeneration, neurotrophins may cause neuronal hyperexcitability that triggers neuropathic pain. In this work, we demonstrate that an early increasing-intensity treadmill exercise (iTR), performed during the first week (iTR1) or during the first 2 weeks (iTR2) after section and suture repair of the rat sciatic nerve, significantly reduced the hyperalgesia developing rapidly in the saphenous nerve territory and later in the sciatic nerve territory after regeneration. Nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) expression in sensory neurons and spinal cord was reduced in parallel. iTR prevented the extension of collateral sprouts of saphenous nociceptive calcitonin gene-related peptide fibers within the adjacent denervated skin and reduced NGF expression in the same skin and in the L3 dorsal root ganglia (DRG). Injury also induced Na-K-2Cl cotransporter 1 (NKCC1) upregulation in DRG, and K-Cl cotransporter 2 (KCC2) downregulation in lumbar spinal cord dorsal horn. iTR normalized NKCC1 and boosted KCC2 expression, together with a significant reduction of microgliosis in L3-L5 dorsal horn, and a reduction of BDNF expression in microglia at 1 to 2 weeks postinjury. These data demonstrate that specific activity protocols, such as iTR, can modulate neurotrophins expression after peripheral nerve injury and prevent neuropathic pain by blocking early mechanisms of sensitization such as collateral sprouting and NKCC1/KCC2 disregulation.

• Effects of Electroacupuncture with Dominant Frequency at SP 6 and ST 36 Based on Meridian Theory on Pain-depression Dyad in Rats (2015)
Effects of Electroacupuncture with Dominant Frequency at SP 6 and ST 36 Based on Meridian Theory on Pain-depression Dyad in Rats
Yuan-yuan Wu, Yong-liang Jiang, Xiao-fen He, Xiao-yun Zhao, Xiao-mei Shao, Jun-ying Du, and Jian-qiao Fang
Department of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China
Published in "Evidence-Based Complementary and Alternative Medicine" (2015-02-16)

Epidemic investigations reveal an intimate interrelationship between pain and depression. The effect of electroacupuncture (EA) on pain or depression has been demonstrated individually, but its effect on pain-depression dyad is unknown. Our study aimed to screen a dominant EA frequency on pain-depression dyad and determine the validity of acupoint selection based on meridian theory. The pain-depression dyad rat model was induced by reserpine and treated using EA with different frequencies at identical acupoints to extract a dominant frequency and then administrated dominant-frequency EA at different acupoints in the above models. Paw withdrawal latency (PWL), emotional behavior of elevated zero maze (EZM) test, and open field (OF) test were conducted. We found that 100?Hz EA at Zusanli (ST 36) and Sanyinjiao (SP 6) (classical acupoints for spleen-deficiency syndrome) were the most effective in improving PWL, travelling distance in the EZM, and maximum velocity in OF compared to EA with other frequencies; ST 36 and SP 6 were proved more effective than other acupoints beyond the meridian theory and nonacupoints under the same administration of EA. Therefore, we concluded that 100?Hz is the dominant frequency for treating the pain-depression dyad with EA, and acupoints on spleen and stomach meridians are preferable choices.

• Buccal acetaminophen provides fast analgesia: two randomized clinical trials in healthy volunteers (2014)
Buccal acetaminophen provides fast analgesia: two randomized clinical trials in healthy volunteers
Gisèle Pickering, Nicolas Macian, Frédéric Libert, J Michel Cardot, Séverine Coissard, Philippe Perovitch, Marc Maury and Claude Dubray
CHU Clermont-Ferrand, Centre de Pharmacologie Clinique, Clermont-Ferrand, France
Published in "Drug Des Devel Ther." (2014-09-26)

Background
Acetaminophen (APAP) by oral or intravenous (iv) routes is used for mild to moderate pain but may take time to be effective. When fast relief is required and/or oral or iv routes are not available because of the patient’s condition, the transmucosal route may be an alternative.

Methodology
A new transmucosal/buccal (b) pharmaceutical form of APAP dissolved in 50% wt alcohol is compared with other routes of administration. Two consecutive randomized, crossover, double-blind clinical trials (CT1: NCT00982215 and CT2: NCT01206985) included 16 healthy volunteers. CT1 compared the pharmacology of 250 mg bAPAP with 1 g iv APAP. CT2 compared the pharmacodynamics of 125 mg bAPAP with 1 g iv and 125 mg sublingual (s) APAP. Mechanical pain thresholds are recorded in response to mechanical stimuli applied on the forearm several times during 120 minutes. The objective is to compare the time of onset of antinociception and the antinociception (area under the curve) between the routes of administration with analysis of variance (significance P<0.05).

Results
bAPAP has a faster time of antinociception onset (15 minutes, P<0.01) and greater antinociception at 50 minutes (P<0.01, CT1) and 30 minutes (P<0.01, CT2) than ivAPAP and sAPAP. All routes are similar after 50 minutes.

Conclusion
bAPAP has a faster antinociceptive action in healthy volunteers. This attractive alternative to other routes would be useful in situations where oral or iv routes are not available. This finding must now be confirmed in patients suffering from acute pain of mild and moderate intensity.

• Local and remote immune-mediated inflammation after mild peripheral nerve compression in rats. (2013)
Local and remote immune-mediated inflammation after mild peripheral nerve compression in rats.
A.B. Schmid, M.W. Coppieters, M.J. Ruitenberg, E.M. McLachlan
School of Health and Rehabilitation Sciences, The University of Queensland, Queensland, Australia
Published in "Journal of Neuropathology & Experimental Neurology" (2013-07-31)

After experimental nerve injuries that extensively disrupt axons, such as chronic constriction injury, immune cells invade the nerve, related dorsal root ganglia (DRGs), and spinal cord, leading to hyperexcitability, raised sensitivity, and pain. Entrapment neuropathies, such as carpal tunnel syndrome, involve minimal axon damage, but patients often report widespread symptoms. To understand the underlying pathology, a tube was placed around the sciatic nerve in 8-week-old rats, leading to progressive mild compression as the animals grew. Immunofluorescence was used to examine myelin and axonal integrity, glia, macrophages, and T lymphocytes in the nerve, L5 DRGs, and spinal cord after 12 weeks. Tubes that did not constrict the nerve when applied caused extensive and ongoing loss of myelin, together with compromise of small-, but not large-, diameter axons. Macrophages and T lymphocytes infiltrated the nerve and DRGs. Activated glia proliferated in DRGs but not in spinal cord. Histologic findings were supported by clinical hyperalgesia to blunt pressure and cold allodynia. Tubes that did not compress the nerve induced only minor local inflammation. Thus, progressive mild nerve compression resulted in chronic local and remote immune-mediated inflammation depending on the degree of compression. Such neuroinflammation may explain the widespread symptoms in patients with entrapment neuropathies.



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Measurement range 0 to 500 grams (5N)
Resolution 0,1gram
Accuracy 0,2 gram
Overload 120 % without causing any damage to the sensor
Temperature Compensation from 0 to 50°C.
Display Extra Large and easy to read multilines - backlighted LCD
PEAK value and CURRENT value on the same screen
Bargraph of capacity
Result: sensitivity threshold = max value
Statistical functions Average value and standard deviation are computed for each subject
Internal Memory up to 100 values
Power supply 220-240 V (other voltages on request)

Model:
BIO-EVF5
Electronic Von Frey 5 with embedded camera
With embedded camera - for rats and mice Contact us

Accessories :
BIO-PVF
Modular holder cages for rats and mice
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Bioseb - In Vivo Research Instruments
Phone worldwide : +33 442 344 360 - USA/Canada : (727) 521-1808
e-Mail : Worldwide: info@bioseb.com - USA/Canada: info-us@bioseb.com