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(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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  • HCUGE Geneve, Suisse
  • BIOCODEX Compiegne, France
  • CHU Tours, France
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  • INSERM FACULTE DE MEDECINE Paris & Clermont-Ferrand, France
  • MEDIMMUNE Cambridge, Royaume Unis
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  • ABBOTT Louvain la neuve, Belgique
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  • SANOFI AVENTIS Vitry sur Seine, Toulouse, Rueil Malmaison, Bagneux, Paris, Montpellier, France
  • ESCPI Paris, France
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! NEW RESEARCH WORK ! A recent publication by K. Salat, M. Kolaczkowski, A. Furgala, A. Rojek, J. Sniecikowska, M. Varney, A. Newman-Tancredi in "Neuropharmacology" highlights the merits of using Bioseb's Electronic Von Frey: Antinociceptive, antiallodynic and antihyperalgesic effects of the 5-HT1A receptor selective agonist, NLX-112 in mouse models of pain

Antinociceptive, antiallodynic and antihyperalgesic effects of the 5-HT1A receptor selective agonist, NLX-112 in mouse models of pain
K. Salat, M. Kolaczkowski, A. Furgala, A. Rojek, J. Sniecikowska, M. Varney, A. Newman-Tancredi
Jagiellonian University, Medical College, Krakow, Poland
Published in "Neuropharmacology" (2017-07-22)


Alterations in transcriptional and translational mechanisms occur during skeletal muscle aging and such changes may contribute to age-related atrophy. Herein, we examined markers related to global transcriptional output (i.e., myonuclear number, total mRNA and RNA pol II levels), translational efficiency [i.e., eukaryotic initiation and elongation factor levels and muscle protein synthesis (MPS) levels] and translational capacity (ribosome density) in the slow-twitch soleus and fast-twitch plantaris muscles of male Fischer 344 rats aged 3, 6, 12, 18, and 24 months (n = 9-10 per group). We also examined alterations in markers of proteolysis and oxidative stress in these muscles (i.e., 20S proteasome activity, poly-ubiquinated protein levels and 4-HNE levels). Notable plantaris muscle observations included: (a) fiber cross sectional area (CSA) was 59% (p < 0.05) and 48% (p < 0.05) greater in 12 month vs. 3 month and 24 month rats, respectively, suggesting a peak lifetime value near 12 months and age-related atrophy by 24 months, (b) MPS levels were greatest in 18 month rats (p < 0.05) despite the onset of atrophy, (c) while regulators of ribosome biogenesis [c-Myc and upstream binding factor (UBF) protein levels] generally increased with age, ribosome density linearly decreased from 3 months of age and RNA polymerase (Pol) I protein levels were lowest in 24 month rats, and d) 20S proteasome activity was robustly up-regulated in 6 and 24 month rats (p < 0.05). Notable soleus muscle observations included: (a) fiber CSA was greatest in 6 month rats and was maintained in older age groups, and (b) 20S proteasome activity was modestly but significantly greater in 24 month vs. 3/12/18 month rats (p < 0.05), and (c) total mRNA levels (suggestive of transcriptional output) trended downward in older rats despite non-significant between-group differences in myonuclear number and/or RNA Pol II protein levels. Collectively, these findings suggest that plantaris, not soleus, atrophy occurs following 12 months of age in male Fisher rats and this may be due to translational deficits (i.e., changes in MPS and ribosome density) and/or increases in proteolysis rather than increased oxidative stress and/or alterations in global transcriptional mechanisms.

Glutamatergic dysfunctions are observed in the pathophysiology of depression. The glutamatergic synapse as well as the AMPA receptor's (AMPAR) activation may represent new potential targets for therapeutic intervention in the context of major depressive disorders. S 47445 is a novel AMPARs positive allosteric modulator (AMPA-PAM) possessing procognitive, neurotrophic properties and enhancing synaptic plasticity. Here, we investigated the antidepressant/anxiolytic-like effects of S47445 in a mouse model of anxiety/depression based on chronic corticosterone administration (CORT) and in the Chronic Mild Stress (CMS) model in rats. Four doses of S 47445 (0.3 to 10 mg/kg, oral route, 4 and 5 weeks, respectively) were assessed in both models. In mouse, behavioral effects were tested in various anxiety-and depression-related behaviors : the elevated plus maze (EPM), open field (OF), splash test (ST), forced swim test (FST), tail suspension test (TST), fur coat state and novelty suppressed feeding (NSF) as well as on hippocampal neurogenesis and dendritic arborization in comparison to chronic fluoxetine treatment (18 mg/kg, p.o.). In rats, behavioral effectsof S 47445 were monitored using sucrose consumption and compared to those of imipramine or venlafaxine (10 mg/kg, i.p.) during the whole treatment period and after withdrawal of treatments. In a mouse model of genetic ablation of hippocampal neurogenesis (GFAP-Tk model), neurogenesisdependent/independent effects of chronic S 47445 treatment were tested, as well as BDNF hippocampal expression. S 47445 reversed CORT-induced depressive-like state by increasing grooming duration and reversing coat state's deterioration. S 47445 also decreased the immobility duration

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:

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)

- 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)

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.

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.

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.

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)

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.

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).

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.

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)

Electronic Von Frey (Modif.)
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