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SMALGO:
SMALL ANIMAL ALGOMETER
(Model: BIO-SMALGO)
Dedicated to small animals, like mice and rats, Smalgo is a pressure-based analgesimeter designed for easy assessment of sensitivity threshold. It is a must for osteo-arthritis and pain studies. A quick, easy-to-use and reliable instrument to assess threshold sensitivity of the animal when applying a progressive force, which can also be used for drug screening, phenotyping, as well as on studies about neuropathy, inflammation and post-operative pain.

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! NEW RESEARCH WORK ! A recent publication by S Ni, Z Ling, X Wang, Y Cao, T Wu, R Deng, JL Crane et al in "Nature Communications" highlights the merits of using Bioseb's SMALGO: SMall animal ALGOmeter: Sensory innervation in porous endplates by Netrin-1 from osteoclasts mediates PGE2-induced spinal hypersensitivity in mice

Sensory innervation in porous endplates by Netrin-1 from osteoclasts mediates PGE2-induced spinal hypersensitivity in mice
S Ni, Z Ling, X Wang, Y Cao, T Wu, R Deng, JL Crane et al
Department of Orthopaedic Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA
Published in "Nature Communications" (2019-12-10)


Spinal pain is a major clinical problem, however, its origins and underlying mechanisms remain unclear. Here we report that in mice, osteoclasts induce sensory innervation in the porous endplates which contributes to spinal hypersensitivity in mice. Sensory innervation of the porous areas of sclerotic endplates in mice was confirmed. Lumbar spine instability (LSI), or aging, induces spinal hypersensitivity in mice. In these conditions, we show that there are elevated levels of PGE2 which activate sensory nerves, leading to sodium influx through Nav 1.8 channels. We show that knockout of PGE2 receptor 4 in sensory nerves significantly reduces spinal hypersensitivity. Inhibition of osteoclast formation by knockout Rankl in the osteocytes significantly inhibits LSI-induced porosity of endplates, sensory innervation, and spinal hypersensitivity. Knockout of Netrin-1 in osteoclasts abrogates sensory innervation into porous endplates and spinal hypersensitivity. These findings suggest that osteoclast-initiated porosity of endplates and sensory innervation are potential therapeutic targets for spinal pain.
Presentation

Bioseb's SMALGO: SMall animal ALGOmeter - demonstration on a rat
SMall Animal ALGOmeter:
Demonstration on a rat
Bioseb’s SMALGO (SMall animal ALGOmeter) is a new pressure-based analgesimeter especially designed for small animals like rats and mice.

Bioseb’s SMALGO fits on your finger (thumb or index) and allows you to easily apply a force or pressure on the desired location. Designed for OA quantification, it is generally used on the knee joint or on the lumbar vertebrae for low back pain assessment.

The threshold sensitivity of the animal (rats or mice) is quickly and reliably determined by applying a progressive force. The threshold is immediately displayed on the electronic device and can be shown in Grams, Newton, Ibs or Oz.

The instrument is composed of :
• The stimulator unit designed to be attached to the thumb delivered with 3 stimulation tips (3,5 and 8 mm in diameter)
• A new interface table casing: This control unit is now the same as other mechanical pain stimulation instruments from Bioseb (Rodent Pincher, Electronic Von Frey..). This compatibility allows the use of one unit for several instruments (economical solution). Moreover, a new feature is available : the Smalgo is now able to deliver TTL signals for electrophysiology applications.
• The BIO-CIS Software for connection to a computer.

Operating principle

The operator adjusts the algometer (analgesimeter) to the thumb and applies a progressive pressure to the relevant location on the animal, as if he was applying the pressure directly with his own finger. The operator increases the stimulation until he obtains a reaction from the animal (scream, shudder...) and then stops the stimulation. The maximum force value is automatically saved and displayed on the screen of the instrument.

The sensor provides a capacity of 1500 grams with an accuracy of 0,1%, allowing reliable measurements for a large amount of applications on both rats and mice. It is possible to set an alarm to be triggered when a certain force value is reached, in oder to protect the animal (not overstimulate them) as well as the sensor (not overload it).

You can also connect the Smalgo to ourBIO-CIS software. There are two ways of using Smalgo with this software :
• The Smalgo can be connected directly to the software during the experiment. Bio-Cis will display force curves in real-time during every measurement, which is a great help to ensure repeatability during your stimulations and to validate your data.
• You can also export all measurements stored in the inner memory of the Smalgo after the experiment.
In both cases, you will furthermore be able to export your results to an Excel file.

Key features

• Easy-to-use and reliable
• Works for both rats and mice
• Can be used to determine pain threshold with a progressive force
• Able to send TTL results for electrophysiology
Domains of application

• Osteo-arthritis
• Drug screening
• Phenotyping
• Neuropathy
• Inflammation
• Post-operative pain
Customers

• Laboratoire Biocodex, France
• Rush University, Chicago, USA
• North Carolina State University, USA
• University Complutense of Madrid, Madrid, Spain
• Chosun University, Korea

Supplied with

• Carry case, mains adaptor 110/220 V
• Control unit and its sensor (cable is 1 meter long)
• 3 sensor tips 3, 5, 8 mm diam.
• Software BIO-CIS included to display force curves and transfert data under MS Excel data sheet
• RS-232-USB cable to plug it to a laptop under Windows OS
• USB footswitch to reset the display hand-free

Bioseb's BIO-CIS Software for the SMALGO: SMall animal ALGOmeter
BIO-CIS Software for the SMall animal ALGOmeter
New features

Enhanced compatibility: The Smalgo control unit is now the same as other mechanical pain stimulators from Bioseb.
Economical solution if you want to buy several mechanical pain stimulators.
All in one instrument reducing space in your laboratory.
Easy maintenance : Only one instrument to re-calibrate.
Also, for users already owning the Bioseb Von frey (EVF4) or Pincher, the SMALGO sensor is available as an “add on” part to their instrument. (Ref: SMALGO-SPIP ).

TTL Option: For laboratories that need compatibility between Smalgo and Electrophysiology, Bioseb allows the instrument to send TTL Signals between 0 and 5 volts. • Smalgo now enables you to pair electrophysiology signals and pain stimulation.
• The operator can define a limit in force at which the Smalgo will send the trigger. The trigger can be sent when reaching one or several values. This is a very convenient feature for a large number of protocols.
• The TTL trigger is easy to set up directly in the menu of the apparatus (without needing to connect to the software)
• A sound and a light can be activated at a specific force. Several possibilities are available. Do not hesitate to contact us for this option.

Foot switch: With Smalgo, it is now possible to reset the value (tar/reset to zero) with a foot switch, allowing the operator to keep his both hands to manipulate the animal. The foot switch is systematically delivered with the Smalgo.

Dedicated software

The Bioseb’s BIO-CIS software sends data acquired via the SMall Animal AlGOmeter into a MS Excel sheet using the RS232-USB port. Easy to set up, this software interface uses the full power of MS Excel functions, to let you create statistical tables and graphics.

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 -
Sensory innervation in porous endplates by Netrin-1 from osteoclasts mediates PGE2-induced spinal hypersensitivity in mice (2019)
Sensory innervation in porous endplates by Netrin-1 from osteoclasts mediates PGE2-induced spinal hypersensitivity in mice
S Ni, Z Ling, X Wang, Y Cao, T Wu, R Deng, JL Crane et al
Department of Orthopaedic Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA
Published in "Nature Communications" (2019-12-10)

Spinal pain is a major clinical problem, however, its origins and underlying mechanisms remain unclear. Here we report that in mice, osteoclasts induce sensory innervation in the porous endplates which contributes to spinal hypersensitivity in mice. Sensory innervation of the porous areas of sclerotic endplates in mice was confirmed. Lumbar spine instability (LSI), or aging, induces spinal hypersensitivity in mice. In these conditions, we show that there are elevated levels of PGE2 which activate sensory nerves, leading to sodium influx through Nav 1.8 channels. We show that knockout of PGE2 receptor 4 in sensory nerves significantly reduces spinal hypersensitivity. Inhibition of osteoclast formation by knockout Rankl in the osteocytes significantly inhibits LSI-induced porosity of endplates, sensory innervation, and spinal hypersensitivity. Knockout of Netrin-1 in osteoclasts abrogates sensory innervation into porous endplates and spinal hypersensitivity. These findings suggest that osteoclast-initiated porosity of endplates and sensory innervation are potential therapeutic targets for spinal pain.

An endocannabinoid uptake inhibitor from black pepper exerts pronounced anti-inflammatory effects in mice (2017)
An endocannabinoid uptake inhibitor from black pepper exerts pronounced anti-inflammatory effects in mice
I.R. Moreno, I. Najar-Guerrero, N. Escareno, M.E. Flores, J. Gertsch, J.M. Viveros-Paredes
Departamento de Farmacologi?a, Centro Universitario de Ciencias Exactas e Ingenieri?as, Universidad de Guadalajara, Jalisco, Me?xico
Published in "Journal of Agriculture and Food Chemistry" (2017-09-24)

Guineensine is a dietary N-isobutylamide widely present in black and long pepper (Piper nigrum and P. longum) previously shown to inhibit cellular endocannabinoid uptake. Given the role of endocannabinoids in inflammation and pain reduction, here we evaluated guineensine in mouse models of acute and inflammatory pain and endotoxemia. Significant dose-dependent anti-inflammatory effects (95.6 ± 3.1 % inhibition of inflammatory pain at 2.5 mg/kg i.p. and 50.0 ± 15.9 % inhibition of edema formation at 5 mg/kg i.p.) and acute analgesia (66.1 ± 28.1 % inhibition at 5.0 mg/kg i.p.) were observed. Moreover, guineensine inhibited pro-inflammatory cytokine production in endotoxemia. Intriguingly, guineensine and LPS independently induced catalepsy but in combination this effect was abolished. Both hypothermia and analgesia were blocked by the CB1 receptor inverse agonist rimonabant but the pronounced hypolocomotion was CB1 receptor-independent. A subsequent screen of 45 CNS-related receptors, ion channels and transporters revealed apparent interactions of guineensine with the dopamine transporter DAT, 5HT2A and sigma receptors, uncovering its prospective polypharmacology. The described potent pharmacological effects of guineensine might relate to the reported anti-inflammatory effects of pepper.

- Mechanical allodynia & hyperlagesia -
Development of an Experimental Animal Model for Lower Back Pain by Percutaneous Injury-Induced Lumbar Facet Joint Osteoarthritis (2015)
Development of an Experimental Animal Model for Lower Back Pain by Percutaneous Injury-Induced Lumbar Facet Joint Osteoarthritis
Kim JS, Ahmadinia K, Li X, Hamilton JL, Andrews S, Haralampus CA, Xiao G, Sohn HM, You JW, Seo YS, Stein GS8, Van Wijnen AJ, Kim SG, Im HJ
The Division of Natural Medical Sciences, College of Health Science, Chosun University, Gwangju, Republic of Korea.
Published in "J Cell Physiol." (2015-11-01)

We report generation and characterization of pain-related behavior in a minimally invasive facet joint degeneration (FJD) animal model in rats. FJD was produced by a non-open percutaneous puncture-induced injury on the right lumbar FJs at three consecutive levels. Pressure hyperalgesia in the lower back was assessed by measuring the vocalization response to pressure from a force transducer. After hyperalgesia was established, pathological changes in lumbar FJs and alterations of intervertebral foramen size were assessed by histological and imaging analyses. To investigate treatment options for lumber FJ osteoarthritis-induced pain, animals with established hyperalgesia were administered with analgesic drugs, such as morphine, a selective COX-2 inhibitor, a non-steroidal anti-inflammatory drug (NSAID) (ketorolac), or pregabalin. Effects were assessed by behavioral pain responses. One week after percutaneous puncture-induced injury of the lumbar FJs, ipsilateral primary pressure hyperalgesia developed and was maintained for at least 12 weeks without foraminal stenosis. Animals showed decreased spontaneous activity, but no secondary hyperalgesia in the hind paws. Histopathological and microfocus X-ray computed tomography analyses demonstrated that the percutaneous puncture injury resulted in osteoarthritis-like structural changes in the FJs cartilage and subchondral bone. Pressure hyperalgesia was completely reversed by morphine. The administration of celecoxib produced moderate pain reduction with no statistical significance while the administration of ketorolac and pregabalin produced no analgesic effect on FJ osteoarthritis-induced back pain. Our animal model of non-open percutanous puncture-induced injury of the lumbar FJs in rats shows similar characteristics of low back pain produced by human facet arthropathy.

Nefopam and ketoprofen synergy in rodent models of antinociception. (2008)
Nefopam and ketoprofen synergy in rodent models of antinociception.
P. Girard, D. Verniers, M.-C. Coppé, Y. Pansart, J.-M. Gillardin.
Biocodex, Service de Pharmacologie, Compičgne, France.
Published in "European Journal of Pharmacology" (2008-04-28)

Combinations of analgesics with different mechanisms of action offer the possibility of efficient analgesia with a decrease in side effects as a result of reduced dosages of one or both compounds. Based on a clinical observation of synergism between nefopam, a centrally acting non-opioid that inhibits monoamines reuptake, and ketoprofen, a non-steroidal anti-inflammatory drug, the objective of this study was to further explore this antinociceptive synergy in four distinct animal models of pain (both drugs were administered subcutaneously). Strong antinociceptive properties were observed in the mouse writhing abdominal test with ED50 values of 2.56 ± 0.38 and 1.41 ± 0.41 mg/kg for nefopam and ketoprofen, respectively. In the inflammatory phase of the mouse formalin test, both compounds significantly inhibited the licking time of the injected hind-paw with ED50 of 4.32 ± 0.17 mg/kg for nefopam and 49.56 ± 15.81 mg/kg for ketoprofen. Isobolographic analysis revealed that this drug combination is synergistic in the formalin test and additive in the writhing test. In rat carrageenan-induced tactile allodynia, single administration of nefopam or ketoprofen only partially reduced allodynia. Combination of low analgesic doses of nefopam (10 or 30 mg/kg) with low analgesic doses of ketoprofen (30 or 100 mg/kg) significantly reduced or reversed allodynia, with a more pronounced anti-allodynic effect and a longer duration efficacy. In a rat model of postoperative thermal hyperalgesia induced by incision, co-administration of nefopam at a low analgesic dose (10 mg/kg) with ketoprofen at non-analgesic doses (30 or 100 mg/kg) showed the appearance of a strong anti-hyperalgesic effect, maintained during at least 3 h. In conclusion, co-administration of nefopam with ketoprofen is synergistic, and should allow either to increase their analgesic efficacy and/or to reduce their side effects.

Nefopam potentiates morphine antinociception in allodynia and hyperalgesia in the rat. (2004)
Nefopam potentiates morphine antinociception in allodynia and hyperalgesia in the rat.
P. Girard, Y. Pansart, J.-M. Gillardin.
Laboratoires Biocodex, Service de Pharmacologie, Compičgne, France.
Published in "Pharmacology Biochemistry and Behavior" (2004-04-30)

The objective of this study was to resolve discrepancies regarding the possible antinociceptive synergy between morphine and nefopam in animal models of pain. Firstly, we have examined the antinociceptive activity of nefopam, a nonopioid antinociceptive compound that inhibits monoamine reuptake, in pain models of allodynia and hyperalgesia induced by carrageenan injection, or skin and muscle incision of the rat hind paw. Single subcutaneous administration of nefopam at 30 mg/kg blocked carrageenan- and incision-induced thermal hyperalgesia, and weakly but significantly diminished carrageenan-induced tactile allodynia. A weaker dose of nefopam (10 mg/kg) only reduced carrageenan-induced tactile allodynia and incision-induced thermal hyperalgesia. Secondly, we assessed the usefulness of the coadministration of nefopam with morphine. Combination of a nonanalgesic dose of nefopam (10 mg/kg) with a nonanalgesic dose of morphine (0.3 or 1.0 mg/kg) completely inhibited carrageenan- or incision-induced thermal hyperalgesia, respectively. In carrageenan-induced tactile allodynia, coadministration of weak analgesic doses of nefopam (10 and 30 mg/kg) with a nonanalgesic dose (1 mg/kg) or moderately analgesic dose (3 mg/kg) of morphine significantly reduced or reversed allodynia, respectively. In conclusion, coadministration of nefopam with morphine enhances the analgesic potency of morphine, indicating a morphine sparing effect of nefopam.

- Inflammatory pain -
An endocannabinoid uptake inhibitor from black pepper exerts pronounced anti-inflammatory effects in mice (2017)
An endocannabinoid uptake inhibitor from black pepper exerts pronounced anti-inflammatory effects in mice
I.R. Moreno, I. Najar-Guerrero, N. Escareno, M.E. Flores, J. Gertsch, J.M. Viveros-Paredes
Departamento de Farmacologi?a, Centro Universitario de Ciencias Exactas e Ingenieri?as, Universidad de Guadalajara, Jalisco, Me?xico
Published in "Journal of Agriculture and Food Chemistry" (2017-09-24)

Guineensine is a dietary N-isobutylamide widely present in black and long pepper (Piper nigrum and P. longum) previously shown to inhibit cellular endocannabinoid uptake. Given the role of endocannabinoids in inflammation and pain reduction, here we evaluated guineensine in mouse models of acute and inflammatory pain and endotoxemia. Significant dose-dependent anti-inflammatory effects (95.6 ± 3.1 % inhibition of inflammatory pain at 2.5 mg/kg i.p. and 50.0 ± 15.9 % inhibition of edema formation at 5 mg/kg i.p.) and acute analgesia (66.1 ± 28.1 % inhibition at 5.0 mg/kg i.p.) were observed. Moreover, guineensine inhibited pro-inflammatory cytokine production in endotoxemia. Intriguingly, guineensine and LPS independently induced catalepsy but in combination this effect was abolished. Both hypothermia and analgesia were blocked by the CB1 receptor inverse agonist rimonabant but the pronounced hypolocomotion was CB1 receptor-independent. A subsequent screen of 45 CNS-related receptors, ion channels and transporters revealed apparent interactions of guineensine with the dopamine transporter DAT, 5HT2A and sigma receptors, uncovering its prospective polypharmacology. The described potent pharmacological effects of guineensine might relate to the reported anti-inflammatory effects of pepper.



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Measuring Range 0 to 1500 grams (15 N)
Sensitivity 0.1 gram or 0.01 N
Tips 3, 5 or 8 mm in Diameter (stainless steel)
Sampling speed Automatically detect the respond to pain at 1000 Hz
Overload protection 200%
Display Extra-large to read both Peak (threshold) applied force
and Current Force value.
Memory SMALGO includes internal memory for 100 measures .
Easy to use internal statistic package for a quick check between animal groups.
Output to PC via RS232-USB and BIO-CIS dedicated software.
Power from the Main or using the embedded rechargeable battery (8 hours)

Model:
BIO-SMALGO
SMALGO: SMall animal ALGOmeter
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Accessories :
BIO-CIS
Bioseb CIS Software
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MMG-XS
Armour Touch Metal Mesh Glove
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