Home > Catalog > Pain - Mechanical allodynia / Hyperalgesia
Product
Category
RODENT PINCHER - ANALGESIA METER
(Model: BIO-RPR - For rats)
A fast and accurate algometer based on an instrumented pincher as an alternative to the Randall-Selitto test: This new analgesia meter developed by Bioseb following Luis-Delgado et al. (2005) allows accurate nociceptive tests to measure mechanical pain threshold on rat or mouse limbs with minimal constraint.

- More information - - Documents - - Contact Bioseb -
Users
Publications
Technical specifications
Other products / accessory  
  • UNIVERSITY OF MANITOBA Winnipeg, Canada
  • VERTEX PHARMACEUTICALS San Diego, USA
  • DUKE UNIVERSITY MEDICAL CENTER Durham, USA
  • MC MASTER UNIVERSITY Hamilton, Canada
  • PFIZER Sandwich, UK
  • INNSBRUCK MEDICAL UNIVERSITY Innsbruck, Austria
  • HARVARD MEDICAL SCHOOL Charlestown, USA
  • UNIL Lausanne, Switzerland
  • CENTRE HOSPITALIER ESQUIROL Limoges, France
  • CNRS UMR 7519 Strasbourg, France
  • ESCPI Paris, France
  • TROPHOS Marseille, France
  • INSERM U 788 Kremlin Bicêtre, France
  • INSTITUT FRANCOIS MAGENDIE Bordeaux, France
  • LABO DE PHYSIOLOGIE ET MANDUCATION Paris, France
  • PHARMALEADS Paris, France
  • SANOFI AVENTIS Vitry Sur Seine, Porcheville, Montpellier & Toulouse, France
  • CNRS, IPMC Valbonne, France
  • BIOCODEX Compiègne, France
  • INSTITUT PASTEUR Paris, France
  • CRSSA La Tronche, France
  • INSTITUT HENRY BEAUFOUR Les Ulis, France
  • PORSOLT AND PARTNERS Le Genest ST Isle, France
  • ASTRAZENECA R&D MONTREAL St Laurent, Canada
  • MEDICAL UNIVERSITY OF VIENNA VIENNA, AUSTRIA
Download PDF
Download video
(Modif.) This page is available in following languages:
! NEW RESEARCH WORK ! A recent publication by Gupta B, Chakraborty S, Saha S, Chandel SG, Baranwal AK, Banerjee M, Chatterjee M, Chaudhury A in "Can J Physiol Pharmacol." highlights the merits of using Bioseb's Rodent pincher - analgesia meter: Anti-nociceptive properties of shikonin: In vitro and In vivo studies

Anti-nociceptive properties of shikonin: In vitro and In vivo studies
Gupta B, Chakraborty S, Saha S, Chandel SG, Baranwal AK, Banerjee M, Chatterjee M, Chaudhury A
Department of Bio and Nano Technology, Bio and Nano Technology Centre, Guru Jambheshwar University of Science and Technology, Hisar 125 001 (Haryana), India.
Published in "Can J Physiol Pharmacol." (2016-07-01)


Shikonin possess a diverse spectrum of pharmacological properties in multiple therapeutic areas. However, the nociceptive effect of shikonin is not largely known. To investigate the antinociceptive potential of shikonin, panel of GPCRs, ion channels, and enzymes involved in pain pathogenesis were studied. To evaluate the translation of shikonin efficacy in vivo, it was tested in 3 established rat pain models. Our study reveals that shikonin has significant inhibitory effect on pan sodium channel/N1E115 and NaV1.7 channel with half maximal inhibitory concentration (IC50) value of 7.6 ?mol/L and 6.4 ?mol/L, respectively, in a cell-based assay. Shikonin exerted significant dose dependent antinociceptive activity at doses of 0.08%, 0.05%, and 0.02% w/v in pinch pain model. In mechanical hyperalgesia model, dose of 10 and 3 mg/kg (intraperitoneal) produced dose-dependent analgesia and showed 67% and 35% reversal of hyperalgesia respectively at 0.5 h. Following oral administration, it showed 39% reversal at 30 mg/kg dose. When tested in first phase of formalin induced pain, shikonin at 10 mg/kg dose inhibited paw flinching by ?71%. In all studied preclinical models, analgesic effect was similar or better than standard analgesic drugs. The present study unveils the mechanistic role of shikonin on pain modulation, predominantly via sodium channel modulation, suggesting that shikonin could be developed as a potential pain blocker.
Presentation

 Changes of the nociceptive hind paw threshold induced by morphine Bioseb's "Rodent Pincher" algometer allows calibrated forceps to induce quantifiable mechanical stimulation in the animal (rats or mice) on a linear scale. The most suitable protocol was experimented by determining the effects of 3 repetitive measurements on the 2 hindpaws, respectively over long-term (9 days), mid-term (1 day) and short-term (2 hours). It was primarily developed as an analgesimeter/algometer (analgesia measurement instrument) for nociceptive tests. In this specific use, the Rodents Pincher not only represents an alternative to the "RANDALL & SELITTO" test - but also presents the following advantages when compared to the classical test:
• More ethical handling, less stressful for the animal (rat or mouse) resulting in less variable measurements
• Faster measurement, less traumatic for the tissues
• Digital measurement with metrological traceability

Furthermore, this pincher-based analgesia meter can also be used for other applications that require a controlled force or pressures values, for example :
• Sensitivity recovery after nerve crush: pinching is applied at several places over the paw to see the sensitivity recovery
• Mechanical injuries for thrombotic models
• Mechanical stimulation for in vivo electrophysiological recordings using the possibility to trigger recording on force thresholds

Comparative studies (including comparative tests with the Randall & Sellito analgesimeter) have demonstrated the accuracy of this pincher-based algometer for easy, fast and reproducible measurement of mechanical pain threshold on rat limbs. Moreover, it allowed to perform rat analagesia testing with minimal constraint, which reduces data variability.


One of these experimental research works was carried out by the team of Prof. Poisbeau in the "Nociception & Pain" department of the "Institut des Neurosciences Cellulaires et Intégratives" (Université Louis pasteur) in Strasbourg.

This work was described in two articles published in December 2005 in international reviews with a controlling committee:

Validation method :
Calibrated Forceps: A Sensitive and Reliable Tool for Pain and Analgesia Studies, by Luis-Delgado et al. in The Journal of pain, December 2005

Scientific work :
Inflammatory Pain Upregulates Spinal Inhibition via Endogenous Neurosteroid Production, by P. Poisbeau et al. in The Journal of neuroscience, December 2005

Click on the title of one of the articles to send a request to download the PDF file

Operating principle

Bioseb's Rodent Pincher Analgesimeter: Embedded statistical computation Bioseb's Rodent Pincher Analgesimeter: Embedded statistical computation The pressure is applied in the "inter-digital" region. When used on the rat the pressure can also be applied to the tail. The instrument displays the force (in grams, newton, oz, lbs) at which the animal reacts and reports the nociception threshold.

Individual pain threshold measurements (up to 100) are stored in the internal memory, and can be downloaded post experiment. Recently an embedded statistical computation has been included in the electronic device of the algometer. This is a very useful feature that as been very well received and used by users of large numbers of tests. The display shows in real time the mean, standard deviation and variation coefficient from groups of animals (rats or mice). This feature also allows the user to cancel any analgesia test incorrectly performed.


Parameters measured

The following parameters are measured by Bioseb's rodents pincher / analgesia instrument:
• Maximum force applied as the animal reacts (movement, vocalization) (in grams, N, oz, lbs)
• Duration of the test (using Bioseb's BIO-CIS software) in seconds


Domains of application

Bioseb's Rodent Pincher Algometer can be used for a variety of research on nociception and analgesia, including:
• In vivo models evaluation of pain
• Mechanisms related to mechanical nociception
• Whenever a calibrated force is necessary

Bioseb's new pincher design: mounting of custom-made bits to suit your most specific needs and analgesia applications
Built-in components

These built-in components will make the analgesia measurement easier:
• Desktop stand for easy reading
• Footswitch to reset the zero of the rodent pincher analgesimeter while keeping hands free.
• RS232 output to transfer displayed data to a PC.
• Our new pincher design allows the mounting of custom-made bits to suit your most specific needs and applications. Please contact us if you have any special request about the pincher, and we'll do our best to cover your needs.


Options

• Our optional BIO-CIS software for Windows sends directly the displayed values in an Excel (MS) sheet. This allows the user direct access to a ready report and options for further analysis, without any re-copy error. Supplied with an RS232 cable.
• External pod to display a led light or produce a sound when reaching a preset threshold of force.
• Analog output and cable
• TTL output
• Additional sensor tests : our Electronic Von Frey probe, Small Animal Algometer come with their own calibration modules that are recognized by the electronic unit.


Supplied with

• Bench control unit (batteries and main power supply)
• One rat or mice pincher, capacity 2000 grs
• Carrying case
• Footswitch for zeroing the force and having the hands "free"
• RS232 output
• User manual


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

PAIN
- General pain -
Corticosterone analgesia is mediated by the spinal production of neuroactive metabolites that enhance GABAergic inhibitory transmission on dorsal horn rat neurons (2015)
Corticosterone analgesia is mediated by the spinal production of neuroactive metabolites that enhance GABAergic inhibitory transmission on dorsal horn rat neurons
Zell V, Juif PÉ, Hanesch U, Poisbeau P, Anton F, Darbon P.
Centre National de la Recherche Scientifique and University of Strasbourg, Institut des Neurosciences Cellulaires et Intégratives, Strasbourg, France
Published in "Eur J Neurosci. " (2015-02-01)

Corticosterone (CORT) is a glucocorticoid produced by adrenal glands under the control of the hypothalamic-pituitary-adrenal axis. Circulating CORT can enter the central nervous system and be reduced to neuroactive 3?5?-reduced steroids, which modulate GABAA receptors. In the dorsal spinal cord, GABAergic transmission modulates integration of nociceptive information. It has been shown that enhancing spinal inhibitory transmission alleviates hyperalgesia and allodynia. Therefore, the spinal neuronal network is a pivotal target to counteract pain symptoms. Thus, any increase in spinal 3?5?-reduced steroid production enhancing GABAergic inhibition should reduce nociceptive message integration and the pain response. Previously, it has been shown that high levels of plasma glucocorticoids give rise to analgesia. However, to our knowledge, nothing has been reported regarding direct non-genomic modulation of neuronal spinal activity by peripheral CORT. In the present study, we used combined in vivo and in vitro electrophysiology approaches, associated with measurement of nociceptive mechanical sensitivity and plasma CORT level measurement, to assess the impact of circulating CORT on rat nociception. We showed that CORT plasma level elevation produced analgesia via a reduction in C-fiber-mediated spinal responses. In the spine, CORT is reduced to the neuroactive metabolite allotetrahydrodeoxycorticosterone, which specifically enhances lamina II GABAergic synaptic transmission. The main consequence is a reduction in lamina II network excitability, reflecting a selective decrease in the processing of nociceptive inputs. The depressed neuronal activity at the spinal level then, in turn, leads to weaker nociceptive message transmission to supraspinal structures and hence to alleviation of pain.

Characterization of the fast GABAergic inhibitory action of etifoxine during spinal nociceptive processing in male rats (2014)
Characterization of the fast GABAergic inhibitory action of etifoxine during spinal nociceptive processing in male rats
Juif PE, Melchior M, Poisbeau P
Centre National de la Recherche Scientifique and University of Strasbourg, Institute of Cellular and Integrative Neurosciences, Strasbourg, France
Published in "Neuropharmacology. " (2014-12-26)

Etifoxine (EFX) is a non-benzodiazepine anxiolytic which potentiate GABAA receptor (GABAAR) function directly or indirectly via the production of 3?-reduced neurosteroids. The later effect is now recognized to account for the long-term reduction of pain symptoms in various neuropathic and inflammatory pain models. In the present study, we characterized the acute antinociceptive properties of EFX during spinal pain processing in naive and monoarthritic rats using in vivo electrophysiology. The topical application of EFX on lumbar spinal cord segment, at concentrations higher than 30 ?M, reduced the excitability of wide dynamic range neurons receiving non-nociceptive and nociceptive inputs. Windup discharge resulting from the repetitive stimulation of the peripheral receptive field, and recognized as a short-term plastic process seen in central nociceptive sensitization, was significantly inhibited by EFX at these concentrations. In good agreement, mechanical nociceptive thresholds were also significantly increased following an acute intrathecal injection of EFX. The acute modulatory properties of EFX on spinal pain processing were never seen in the simultaneous presence of bicuculline. This result further confirmed EFX antinociception to result from the potentiation of spinal GABAA receptor function.

Plasma glucocorticoids differentially modulate phasic and tonic GABA inhibition during early postnatal development in rat spinal lamina II (2014)
Plasma glucocorticoids differentially modulate phasic and tonic GABA inhibition during early postnatal development in rat spinal lamina II
V. Zella, U. Haneschb, P. Poisbeaua, F. Antonb, P. Darbon
Centre National de la Recherche Scientifique and University of Strasbourg, Strasbourg, France
Published in "Neuroscience Letters" (2014-06-23)

Nociceptive processing is tuned by GABAA receptor-mediated inhibition in the spinal cord dorsal horn that undergoes postnatal maturation in rodents. These GABAergic inhibitory postsynaptic currents (IPSCs) are modulated by 3α5α-reduced steroids during early postnatal development in spinal cord lamina II. Thus an enhanced phasic inhibition is present in neonates and decreases over time. GABA can also activate extrasynaptic receptors, giving rise to tonic inhibition. In this study, we characterized the contribution of plasma corticosterone (CORT) to postnatal maturation of spinal phasic and, for the first time, tonic GABAergic inhibitions. We used Fisher and Lewis rat strains displaying respectively high and low hypothalamic-pituitary-adrenal axis reactivity, compared to control Sprague-Dawley rats. Measured plasma CORT levels were significantly higher in Fisher rats, which also displayed significantly higher mechanical nociceptive thresholds, supporting the hypothesis of an antinociceptive action of CORT. Recorded GABAA IPSCs shortened during maturation in all strains while remaining larger in Fisher rats. Blocking the 5α-reduction of steroids in Fisher rats produced a further decrease of IPSC deactivation time constant. In contrast, GABAA tonic inhibition progressively increased during maturation, without any difference among strains. In conclusion, we show that both phasic and tonic GABAergic inhibitions undergo postnatal maturation in lamina II. Moreover spinal production of 3α5α-reduced steroids that presumably derive from plasma CORT is correlated to spinal GABAA phasic (but not tonic) inhibition and to mechanical nociceptive thresholds.

Long-Lasting Spinal Oxytocin Analgesia Is Ensured by the Stimulation of Allopregnanolone Synthesis Which Potentiates GABAA Receptor-Mediated Synaptic Inhibition (2013)
Long-Lasting Spinal Oxytocin Analgesia Is Ensured by the Stimulation of Allopregnanolone Synthesis Which Potentiates GABAA Receptor-Mediated Synaptic Inhibition
P E.Juif,J D.Breton,M.Rajalu,A.Charlet,Y.Goumon
CNRS and University of Strasbourg, Institut des Neurosciences Cellulaires et Intégratives,Strasbourg, France
Published in "The Journal of Neurosciences" (2013-10-16)


Hypothalamospinal control of spinal pain processing by oxytocin (OT) has received a lot of attention in recent years because of its potency to reduce pain symptoms in inflammatory and neuropathic conditions. However, cellular and molecular mechanisms underlying OT spinal antinociception are still poorly understood. In this study, we used biochemical, electrophysiological, and behavioral approaches to demonstrate that OT levels are elevated in the spinal cord of rats exhibiting pain symptoms, 24 h after the induction of inflammation with an intraplantar injection of λ-carrageenan. Using a selective OT receptor antagonist, we demonstrate that this elevated OT content is responsible for a tonic analgesia exerted on both mechanical and thermal modalities. This phenomenon appeared to be mediated by an OT receptor-mediated stimulation of neurosteroidogenesis, which leads to an increase in GABAA receptor-mediated synaptic inhibition in lamina II spinal cord neurons. We also provide evidence that this novel mechanism of OT-mediated spinal antinociception may be controlled by extracellular signal-related protein kinases, ERK1/2, after OT receptor activation. The oxytocinergic inhibitory control of spinal pain processing is emerging as an interesting target for future therapies since it recruits several molecular mechanisms, which are likely to exert a long-lasting analgesia through nongenomic and possibly genomic effects.

Etifoxine stimulates allopregnanolone synthesis in the spinal cord to produce analgesia in experimental mononeuropathy (2013)
Etifoxine stimulates allopregnanolone synthesis in the spinal cord to produce analgesia in experimental mononeuropathy
M. Aouad, N. Petit-Demoulière, Y. Goumon, P. Poisbeau
Institut des Neurosciences Cellulaires et Intégratives, Strasbourg, France
Published in "European Journal of Pain" (2013-07-24)

Background
Pathological pain states are often associated with neuronal hyperexcitability in the spinal cord. Reducing this excitability could theoretically be achieved by amplifying the existing spinal inhibitory control mediated by GABAA receptors (GABAARs). In this study, we used the non-benzodiazepine anxiolytic etifoxine (EFX) to characterize its interest as pain killer and spinal mechanisms of action. EFX potentiates GABAAR function but can also increase its function by stimulating the local synthesis of 3α-reduced neurosteroids (3αNS), the most potent endogenous modulators of this receptor. Methods
The efficacy of EFX analgesia and the contribution of 3αNS were evaluated in a rat model of mononeuropathy. Spinal contribution of EFX was characterized through changes in pain symptoms after intrathecal injections, spinal content of EFX and 3αNS, and expression of FosB-related genes, a marker of long-term plasticity. Results
We found that a 2-week treatment with EFX (>5 mg/kg, i.p.) fully suppressed neuropathic pain symptoms. This effect was fully mediated by 3αNS and probably by allopregnanolone, which was found at a high concentration in the spinal cord. In good agreement, the level of EFX analgesia after intrathecal injections confirmed that the spinal cord is a privileged target as well as the limited expression of FosB/ΔFosB gene products that are highly expressed in persistent pain states. Conclusions
This preclinical study shows that stimulating the production of endogenous analgesics such as 3αNS represents an interesting strategy to reduce neuropathic pain symptoms. Since EFX is already prescribed as an anxiolytic in several countries, a translation to the human clinic needs to be rapidly evaluated.

Phenotyping the function of TRPV1-expressing sensory neurons by targeted axonal silencing. (2013)
Phenotyping the function of TRPV1-expressing sensory neurons by targeted axonal silencing.
C. Brenneis, K. Kistner, M. Puopolo, D. Segal, D. Roberson et al
F.M. Kirby Neurobiology Center, Children's Hospital Boston, Boston, United States of America.
Published in "The Journal of Neuroscience " (2013-01-02)

Specific somatosensations may be processed by different subsets of primary afferents. C-fibers expressing heat-sensitive TRPV1 channels are proposed, for example, to be heat but not mechanical pain detectors. To phenotype in rats the sensory function of TRPV1+ afferents, we rapidly and selectively silenced only their activity, by introducing the membrane-impermeant sodium channel blocker QX-314 into these axons via the TRPV1 channel pore. Using tandem mass spectrometry we show that upon activation with capsaicin, QX-314 selectively accumulates in the cytosol only of TRPV1-expressing cells, and not in control cells. Exposure to QX-314 and capsaicin induces in small DRG neurons a robust sodium current block within 30 s. In sciatic nerves, application of extracellular QX-314 with capsaicin persistently reduces C-fiber but not A-fiber compound action potentials and this effect does not occur in TRPV1−/− mice. Behavioral phenotyping after selectively silencing TRPV1+ sciatic nerve axons by perineural injections of QX-314 and capsaicin reveals deficits in heat and mechanical pressure but not pinprick or light touch perception. The response to intraplantar capsaicin is substantially reduced, as expected. During inflammation, silencing TRPV1+ axons abolishes heat, mechanical, and cold hyperalgesia but tactile and cold allodynia remain following peripheral nerve injury. These results indicate that TRPV1-expressing sensory neurons process particular thermal and mechanical somatosensations, and that the sensory channels activated by mechanical and cold stimuli to produce pain in naive/inflamed rats differ from those in animals after peripheral nerve injury.



THE INFORMATION IN THIS WEB SITE AND IN LINKED PAGES AND DOCUMENTS IS PROVIDED "AS IS" AND DOES NOT CREATE ANY EXPRESS OR IMPLIED WARRANTY ABOUT BIOSEB OR ITS PRODUCTS OR SERVICES.

Information published on this Web Site as well as services, product specifications, availability and prices are subject to change without notice. BIOSEB may also make improvements and/or changes in the products and/or the programs described in this Web Site at any time without notice.

BIOSEB has made reasonable efforts to verify that the information in this Web site was accurate when first published. Such information may contain errors or omissions, however, and it is subject to change without notice. Bioseb does not undertake to update this information to include any such changes or to correct errors or omissions. Bioseb assumes no responsibility for any use of the information in this Web site or for any infringement of patents or other rights of third parties that may result. Certain information may be country-specific and may not apply in all countries.

Animal Rat or mouse (2 different pinchers)
Measuring Range 0 to 2000 grams
Units Grams / newtons
Resolution 0,1 gram or 0,001 N
Results Displays the current applied force and the maximum applied force during the test
Statistic Mean, standard deviation and variation coefficient
Power supply Battery powered, this instrument is autonomous.
Possibility of using a 220V/110V 50hz/60hz adapter.
Data output RS232 for PC or printer
EMC Controlled

Model:
BIO-RPR
Rodent pincher - analgesia meter (Modif.)
For rats Contact us

Related products:
BIO-SMALGO
Contact us
BIO-RPM
For mice Contact us

Accessories :
BIO-CIS
Contact us
Print version

Bioseb - In Vivo Research Instruments
Phone worldwide : +33 442 344 360 - USA/Canada : (727) 521-1808
e-Mail : Worldwide: info@bioseb.com - USA/Canada: sales@eb-instruments.com