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ELECTRONIC VON FREY
(Model: BIO-EVF)
A quick and easy solution based on a simple yet powerful electronic device to determine the mechanical sensitivity threshold in rodents (rats and mice), ideal for your research on analgesia, nociception, neuropahy and post-operative pain. Now with optional embedded video (on the EVF5 version)!

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! NEW RESEARCH WORK ! A recent publication by Radwani H, Lopez-Gonzalez MJ, Cattaert D, Roca-Lapirot O et al. in "J Physiol." highlights the merits of using Bioseb's Electronic Von Frey: Cav1. 2 and Cav1. 3 l?type calcium channels independently control short?and long?term sensitization to pain

Cav1. 2 and Cav1. 3 l?type calcium channels independently control short?and long?term sensitization to pain
Radwani H, Lopez-Gonzalez MJ, Cattaert D, Roca-Lapirot O et al.
University of Bordeaux, Bordeaux, France
Published in "J Physiol." (2016-05-27)


Short-term central sensitization to pain temporarily increases the responsiveness of nociceptive pathways after peripheral injury. In dorsal horn neurons (DHNs), short-term sensitization can be monitored through the study of wind-up. Wind-up, a progressive increase in DHNs response following repetitive peripheral stimulations, depends on the post-synaptic L-type calcium channels. In the dorsal horn of the spinal cord, two L-type calcium channels are present, Cav1.2 and Cav1.3, each displaying specific kinetics and spatial distribution. In the present study, we used a mathematical model of DHNs in which we integrated the specific patterns of expression of each Cav subunits. This mathematical approach reveals that Cav1.3 is necessary for the onset of wind-up, whereas Cav1.2 is not and that synaptically triggered wind-up requires NMDA receptor activation. We then switched to a biological preparation in which we knocked down Cav subunits and confirmed the prominent role of Cav1.3 in both naive and spinal nerve ligation model of neuropathy (SNL). Interestingly, although a clear mechanical allodynia dependent on Cav1.2 expression was observed after SNL, the amplitude of wind-up was decreased. These results were confirmed with our model when adapting Cav1.3 conductance to the changes observed after SNL. Finally, our mathematical approach predicts that, although wind-up amplitude is decreased in SNL, plateau potentials are not altered, suggesting that plateau and wind-up are not fully equivalent. Wind-up and long-term hyperexcitability of DHNs are differentially controlled by Cav1.2 and Cav1.3, therefore confirming that short- and long-term sensitization are two different phenomena triggered by distinct mechanisms.
Presentation

New EVF Software with embedded video
New EVF Software with embedded video

Electronic Von Frey: New stand
Electronic Von Frey: New stand
Bioseb’s new Electronic Von Frey unit EVF is an easy-to-use instrument allowing you to quickly determine the mechanical pain sensitivity threshold in rodents (both rats and mice).

This value can be measured in one single application of the test, and offers a high accuracy and repeatability. The same analgesia equipment will enable you to carry out animal and human studies, with a resolution of 0,1 gram.

Sensibility threshold result is displayed on a large backlighted screen. The electronic instrument does not present any temperature or hygrometry drift, which used to be an issue with the manual version of the filaments.

Thanks to 16 years in marketing electronic Von Frey instruments, Bioseb has designed what will be the next standard for reflex testing on freely moving rodents, now with embedded video (on the EVF5 version)!

Operating principle

The electronic model of Von-Frey filament combines ease-of-use and rapidity for the determination of the mechanical sensitivity threshold in rodent.

Basically, a tip is applied against the central edge of the animal hind paw. Paw withdrawal caused by the stimulation is registered as a response. The corresponding force applied is recorded by the system and displayed on the large backlighted screen of the Von-Frey unit with a resolution of 0.1 grams. A different tip is used for rat (hard plastic tip) and mice (elastic spring tip).

Differently to the procedure using classical Von-Frey filaments, the threshold value can be obtained in only one test, and in a highly reproducible manner. A foot-switch is provided to carry out rapid hands-free experiments.

New features

Screen of an Electronic Von Frey
Stats screen
The new EVF features several new improvements such as:

Embedded video! On the EVF5 model, the paw is now viewed from the screen of a computer or tablet where the plantar surface can be seen in HD. More accurate, this new method is much comfortable for the user and so generates better data
New, non corrosive tips mounted on precision springs that absorb the force of impact and reduce the "touch-on" effect. Spring based tips increase the accuracy of the measurement over their range of bending.
• 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 validation button is now placed right on the stimulator handle, so the operator can more readily store what is considered to be a good withdrawal measurement.

And of course, all the classical features that made our Electronic Von Frey instrument a must for all your research work on pain and nociception:

• Large backlighted LCD screen 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

Real time force curves display on the new Electronic Von Frey Software for rats and mice, by Bioseb
Real time force curves display
The brand new Bioseb EVF software comes with a lot of new features :

Video with target pointer: No more stretching to target the paw
Real-time curve display: immediate display of applied force, which helps for replicable measures
Value assignation to each animal's paw: Special feature for touch screen PC ! Validation in 1 touch (or 1 click)

For Electronic Von Frey without embedded camera, our separate and optional BIO-CIS Software can also be used to automatically record the results on a PC through a RS 232 port.

Parameters measured

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
• Touchscreen tablet for video display
• 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
Domains of application

• Phenotyping
• Neuropathy
• Inflammation
• Post-operative pain
• Phantom pain


A complete product lineup with different options and modules is available in order to match your needs and applications:

BIO-EVF4 BIO-EVF4S BIO-EVF5 BIO-EVF5S BIO-EVF5SC
Handle stimulator without camera x x
Handle stimulator with camera x x x
Electronic x x x x x
Dedicated software BIO-CIS x
Dedicated software BIO-EVF x x x
Mesh Stand and cages x x
Tactile Tablet x


Supplied with

• 10 disposable plastic tips
• 1 spring tip for thresholds between 0 and 10 grams
• Footswitch to reset the display to zero
• Carrying case for transport


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

PAIN
- General pain -
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.

A Randomized, Controlled Trial Validates a Peripheral Supra-Additive Antihyperalgesic Effect of a Paracetamol–Ketorolac Combination. (2011)
A Randomized, Controlled Trial Validates a Peripheral Supra-Additive Antihyperalgesic Effect of a Paracetamol–Ketorolac Combination.
K.I. Lorenzini, M. Besson, Y. Daali, D. Salomon, P. Dayer et al.
University Hospitals of Geneva, Division of Clinical Pharmacology and Toxicology, Geneva, Switzerland.
Published in "Basic and Clinical Pharmacology and Toxicology" (2011-11-06)

The combination of paracetamol with non-steroidal anti-inflammatory drugs (NSAIDs) is widely used; however, the nature and mechanism of their interaction are still debated. A double-blind, pharmacokinetic/pharmacodynamic, randomized, cross-over, placebo-controlled study was carried out in human healthy volunteers. The aim was to explore the existence of a positive interaction between paracetamol 1 g and ketorolac 20 mg administered intravenously on experimental pain models in human beings. The effects of the paracetamol-ketotolac combination were compared with similar doses of respective single analgesic and to placebo on the sunburn model (UVB-induced inflammation), cold pain tolerance and the nociceptive flexion reflex. The kinetics of the plasma concentrations of paracetamol and ketorolac were measured using 2D-liquid chromatography-mass spectrometry. Thirteen volunteers were screened, and 11 completed the study. Ketorolac significantly decreased primary hyperalgesia to heat stimuli compared with paracetamol (p < 0.014). The combination performed better than paracetamol (p < 0.001) and placebo (p < 0.042), increasing heat pain threshold by 1.5°C. The combination radically reduced primary hyperalgesia to mechanical stimulation (39%) compared with placebo (p < 0.002) and single agents (paracetamol p < 0.024 and ketorolac p < 0.032). The combination also reduced, slightly although significantly, the intensity of pain (10%) for the cold pressor test (versus placebo: p < 0.012, paracetamol: p < 0.019 and ketorolac p < 0.004). None of the treatments significantly affected the central models of pain at this dosage level. No pharmacokinetic interactions were observed. These results suggest a supra-additive pharmacodynamic interaction between paracetamol and ketorolac in an inflammatory pain model. The mechanism of this interaction could mainly rely on a peripheral contribution of paracetamol to the effect of NSAIDs.



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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-EVF
Electronic Von Frey (Modif.)
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Accessories :
BIO-CIS
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