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ELECTRONIC VON FREY 4
(Model: BIO-EVF4)
A quick solution to determine the mechanical sensitivity threshold in rodents (mice and rats).

This precise and easy-to-use electronic instrument is a must-have reference for your research in analgesia, nociception, neuro-pathologies and post-operative pain.


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! NEW RESEARCH WORK ! A recent publication by SS Ballon Romero, YC Lee, LJ Fuh, HY Chung et al in "International Journal of Molecular Sciences" highlights the merits of using Bioseb's Electronic Von Frey 4: Analgesic and Neuroprotective Effects of Electroacupuncture in a Dental Pulp Injury Model

Analgesic and Neuroprotective Effects of Electroacupuncture in a Dental Pulp Injury Model
SS Ballon Romero, YC Lee, LJ Fuh, HY Chung et al
Graduate Institute of Acupuncture Science, China Medical University, Taichung, Taiwan
Published in "International Journal of Molecular Sciences" (2020-04-09)


Irreversible pulpitis is an extremely painful condition and its consequence in the central nervous system (CNS) remains unclear. A mouse model of dental pulp injury (DPI) resembles the irreversible pulpitis profile in humans. This study sought to determine whether pain induced by DPI activates microglia and astrocytes in the trigeminal subnucleus caudalis (Vc), as well as increases levels of proinflammatory cytokines, and whether electroacupuncture (EA) can be a potential analgesic and neuroprotective therapy following DPI. Pain behavior was measured via head-withdrawal threshold (HWT) and burrowing behavior at days 1, 3, 7, 14 and 21 after DPI. A marked decrease in HWT and burrowing activity was observed from day 1 to 14 after DPI and no changes were seen on day 21. Microglial and astrocytes activation; along with high cytokine (TNF-alpha, IL-1, and IL-6) levels, were observed in the Vc at 21 days after DPI. These effects were attenuated by verum (local and distal) EA, as well as oral ibuprofen administration. The results suggest that DPI-induced pain and glial activations in the Vc and EA exert analgesic efficacy at both local and distal acupoints. Furthermore, verum (local and distal) EA might be associated with the modulations of microglial and astrocytes activation.
Presentation

16 years of experience in developing instrumentation for the Von-Frey test allows Bioseb to offer a new standard for mechanical sensitivity threshold measurment in rodents (mice and rats).

The Electronic Von Frey was designed to improve results quality and facilitate measurements compared to classical Von Frey filaments, which require several stimulations for each measurement, thus inducing stress in the animals. Our Electronic version determines the mechanical sensitivity in one single measurement.

The measured value is assessed with a resolution of 0.1 grams with a high-precision sensor which reduces the experimentation duration while improving repeatability between series. Results are shown on a large backlit display. The electronic instrument is not subjected to any temperature or hygrometry drift.

The extended measurement range enables you to use the same instrument for different species (rats, mice, humans, etc.).

The latest version of the Electronic Von Frey includes a new, entirely redesigned stimulator handle for an easier and more balanced manipulation. Thanks to the increased comfort, operator fatigue and tension are notably reduced during experimental sessions involving large series of animals. A new, more accurate and rigid sensor is embedded in the handle to decrease sensitivity to the operator's movements.

Operating principles

Our Electronic Von Frey is built around a display unit connected to a stimulator handle. A foot switch is also provided for resetting the measurement, as well as a box of 10 interchangeable plastic tips.

The operator uses the handle to stimulate the target zone with the dedicated tips.

• Stimulation under the rodent's paw:

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. The maximum force applied with the instrument, which corresponds to the necessary value for the paw's withdrawal, is saved into the system's memory and displayed on the electronic screen of the Electronic Von Frey unit with a resolution of 0.1 g. Different tips are used for rats (hard plastic) and mice (soft tips).

• Specific application for human patients :

The instrument version dedicated to human subjects is supplied with a "patient button" allowing the patient under stimulation to freeze the measurement himself on the screen once the desired threshold (either sensitivity or pain) is reached.

New functionalities

Screen of an Electronic Von Frey
Stats screen
The new Bioseb Electronic Von Frey offers numerous, exclusive improvements and new functionalities, among which:

• 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 a more homogenous stimulation. 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 BIO-CIS Software

Dedicated BIO-CIS Software to increase nociceptive tests repeatability
Dedicated BIO-CIS Software
The multi-instrument BIO-CIS Software, by Bioseb, is compatible with all our mechanical allodynia / nociception measurement instruments and allows you to reduce inter-operator variability, which is an issue for these kinds of tests.

BIO-CIS can be used in two different ways with the Electronic Von Frey:

• Direct measurement: When the Electronic Von Frey is connected to the BIO-CIS software during stimulation, the software displays the real-time graph of applied force vs time in real-time. Additional features allows the definition of a theoretical ramp (force/time) with upper-lower limits to be followed and displayed during the measurement and curves of a group of measures can be reloaded and displayed simultaneously for a graphical overview. These options greatly help the operator to improve their skills with the instrument and reduce operator-introduced variability and is useful for generating impactful figures.

• Indirect measurement: The Electronic Von Frey instrument embeds an internal memory allowing you to store up to 100 values measured during your experiments. You will then be able to connect the instrument to the BIO-CIS software and transfer all your results to an Excel spreadsheet.

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, Ibs and Oz
• Measurement from 1 to 500g ! Perfect for any application !
• Quickly determine the mechanical pain sensitivity threshold !

A few options for easier operations

• A patient switch allows to freeze the displayed value when the threshold is reached
• An RS232 interface allows to transfer the displayed value on to a computer
• Our BIO-CIS software allows to write directly on EXCEL7 the value measured (PC with Windows 7 or higher) thus you avoid transcription errors, and get instant report
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
• Optional: "patient button" for use on human subjects.

New system! AlgoKit

AlgoKit Algometer, by Bioseb
AlgoKit
A COMPLETE SOLUTION FOR ALL SITUATIONS
INVOLVING PAIN MEASUREMENT ON RODENTS
MULTIPLE PROBES, ONE CONTROL UNIT AND SOFTWARE APPLICATION

You may consider our new ALGOKIT package to expand the scope of your possibilities. In order to offer an answer to all your requests regarding different situations of pain measurement, Bioseb is proud to present an innovative, complete solution combining our Static Weight Bearing, including its state-of-the art touchscreen, color console, with up to 3 sensors to be chosen among our Electronic Von Frey, Rodent Pincher and Small animal Algometer, all connected to one unique Control Unit.

Features:
• Flexible instrument when a quantitative sensory testing (QST) is needed
• Compatible with our BIO-CIS software to improve repeatability in nociceptive testing


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-EVF4
Electronic Von Frey 4
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Accessories :
BIO-PVF
Modular holder cages for rats and mice
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Bioseb - In Vivo Research Instruments
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