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COLD HOT PLATE TEST
(Model: BIO-CHP)
For testing animal's thermal sensitivity to pain resulting from exposure to heat or cold: the Cold Hot Plate is an innovative instrument opening new investigation fields for your analgesia and nociception research, and a useful tool for analgesic drug screening using rats or mice models.

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  • HARVARD MEDICAL SCHOOL Charlestown, Etats-Unis
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! NEW RESEARCH WORK ! A recent publication by E.O. Abidoye, I Aplakah in "Sokoto Journal of Veterinary Sciences" highlights the merits of using Bioseb's Cold Hot Plate Test: Antinociceptive and antipyretic properties of ethanol extract of Oryza bathii (Poaceae) in wistar rats

Antinociceptive and antipyretic properties of ethanol extract of Oryza bathii (Poaceae) in wistar rats
E.O. Abidoye, I Aplakah
Department of Veterinary Surgery and Radiology, Ahmadu Bello University, Zaria, Nigeria
Published in "Sokoto Journal of Veterinary Sciences" (2017-08-01)


Ethanol extract of Oryza barthii obtained by cold maceration was investigated for antinociceptive and antipyretic activities using the hot plate and brewer’s yeast-induced hyperthermia methods, respectively in adult wistar rats. The medications used as positive control were piroxicam at 20 mg/kg intra-peritoneal (i.p) for the antinociceptive study and aspirin at 100 mg/kg i.p. for the antipyretic study and both induced significant delay in the reaction time of the rats to thermal stimulus and hyperthermia respectively. Oryza barthii (Poaceae) extract administered at dosages of between 125 – 500 mg/kg i.p, significantly delayed the reaction time of rats to thermal stimulus produced by the hot plate and reduced the hyperthermia in a dose-dependent manner. The results showed that O. barthii possesses antinociceptive and antipyretic activities, thus justifying the folklore use of the plant in traditional medicine for the control of fever and can be an alternative medicament in the management of pyrexia.
Presentation

Bioseb’s Cold and Hot Plate Test is an innovative instrument opening new investigation fields for your analgesia research by allowing you to test animal's sensitivity to pain resulting from exposure to heat or cold.

This innovative Analgesia Meter is based on a metal plate which can be heated to 55°C and cooled to -2°C (with an ambient temperature between 20°C and 25°C). An electronic thermostat maintains the plate's temperature and a front panel digital thermometer displays the current plate temperature.

The Bioseb Cold and Hot Plate is designed to be very simple to use and very fast to reach the set temperature (as example From ambient to 4°C, the most used threshold value, it takes less than 10 minutes, and from 4°C to 55°C it takes only 5 minutes). Metrology wise, is accurate to less than 0,5°C (EEC metrology standard) and perfectly constant in the animal holder system. The preset temperature will not change for more than 0,1°C when a 400g rat is placed on the plate, and return to the set temperature is almost immediate.

Bioseb's Cold Hot Plate Test - Software screenshot
Optional software - Screenshot
Operation Principle

The animal's pain sensitivity resulting from exposure to heat or cold is tested by placing the animal (mouse or rat) on the surface of the plate and starting a built-in timer. The operator stops the timer at the instant the animal lifts its paw from the plate, reacting to the discomfort. The front panel timer then displays the number of seconds it took the animal to react. Animal reaction time is a measurement of animal resistance to pain and is used to measure efficacy of analgesics.

The operator can start and stop the timer with the front panel start/stop switch or with the included footswitch, which allows "hands-free" operation.

Dedidcated software

Though it is functional as a stand-alone instrument, the Cold Hot Plate Test Analgesia Meter can also be used with our dedicated optional software, allowing the user to define temperature "ramps" and “loops”. This feature is mainly used for studies with telemetry implants. In addition to displaying the reaction time, the Cold/Hot Plate Analgesia Meter is able to send the same information via USB interface to a computer.

Key features

• Simple to use, fast and accurate
• Can be used as a stand-alone instrument
• Allows testing of sensitivity to both hot and cold stimulus
• Unmatched temperature stability and control for both heat and cold
• Fast reach to set temperatures
• Homogeneous temperature surface
• Practical foot switch timing operation
• Optional Ramp software will allow the user to define temperature ramps and loops (slope in °C/min, start and end points) and store results
Domains of application

• Analgesic drug screening
• Basal pain sensitivity phenotyping
• Integrated supraspinal responses
• Pain sensitivity alterations induced by a specific experimental context change
• Pain sensitivity alterations induced by genetic manipulations
• Animal Models of Nociception (rats and mice)

! METHOD VALIDATION ! Publication

Bioseb team presents its respectful thanks to research team of Prof. Poisbeau (Institut des Neurosciences Cellulaires et Intégratives de Strasbourg), who validated the temperature ramps method used by the Cold and Hot Plate Test during in following study:

Differentiating Thermal Allodynia and Hyperalgesia Using Dynamic Hot and Cold Plate in Rodents, by I. Yalcin, A. Charlet, MJ. Freund-Mercier, M. Barrot and P. Poisbeau, in The Journal of Pain, 2009
(Click here to download this article as a PDF file)


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

PAIN
- General pain -
Antinociceptive and antipyretic properties of ethanol extract of Oryza bathii (Poaceae) in wistar rats (2017)
Antinociceptive and antipyretic properties of ethanol extract of Oryza bathii (Poaceae) in wistar rats
E.O. Abidoye, I Aplakah
Department of Veterinary Surgery and Radiology, Ahmadu Bello University, Zaria, Nigeria
Published in "Sokoto Journal of Veterinary Sciences" (2017-08-01)

Ethanol extract of Oryza barthii obtained by cold maceration was investigated for antinociceptive and antipyretic activities using the hot plate and brewer’s yeast-induced hyperthermia methods, respectively in adult wistar rats. The medications used as positive control were piroxicam at 20 mg/kg intra-peritoneal (i.p) for the antinociceptive study and aspirin at 100 mg/kg i.p. for the antipyretic study and both induced significant delay in the reaction time of the rats to thermal stimulus and hyperthermia respectively. Oryza barthii (Poaceae) extract administered at dosages of between 125 – 500 mg/kg i.p, significantly delayed the reaction time of rats to thermal stimulus produced by the hot plate and reduced the hyperthermia in a dose-dependent manner. The results showed that O. barthii possesses antinociceptive and antipyretic activities, thus justifying the folklore use of the plant in traditional medicine for the control of fever and can be an alternative medicament in the management of pyrexia.

A clinical and mechanistic study of topical borneol-induced analgesia (2017)
A clinical and mechanistic study of topical borneol-induced analgesia
Wang S, Zhang D, Hu J, Jia Q, Xu W, Su D, Song H, Xu Z, Cui J, Zhou M, Yang J, Xiao J
Ion Channel Research and Drug Development Center, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China
Published in "EMBO Molecular Medicine" (2017-06-01)

Bingpian is a time-honored herb in traditional Chinese medicine (TCM). It is an almost pure chemical with a chemical composition of (+)-borneol and has been historically used as a topical analgesic for millennia. However, the clinical efficacy of topical borneol lacks stringent evidence-based clinical studies and verifiable scientific mechanism. We examined the analgesic efficacy of topical borneol in a randomized, double-blind, placebo-controlled clinical study involving 122 patients with postoperative pain. Topical application of borneol led to significantly greater pain relief than placebo did. Using mouse models of pain, we identified the TRPM8 channel as a molecular target of borneol and showed that topical borneol-induced analgesia was almost exclusively mediated by TRPM8, and involved a downstream glutamatergic mechanism in the spinal cord. Investigation of the actions of topical borneol and menthol revealed mechanistic differences between borneol- and menthol-induced analgesia and indicated that borneol exhibits advantages over menthol as a topical analgesic. Our work demonstrates that borneol, which is currently approved by the US FDA to be used only as a flavoring substance or adjuvant in food, is an effective topical pain reliever in humans and reveals a key part of the molecular mechanism underlying its analgesic effect.

Genetic ablation of GINIP-expressing primary sensory neurons strongly impairs Formalin-evoked pain. (2017)
Genetic ablation of GINIP-expressing primary sensory neurons strongly impairs Formalin-evoked pain.
Urien L, Gaillard S, Lo Re L, Malapert P, Bohic M, Reynders A, Moqrich A
"Aix-Marseille-Université, Institut de Biologie du Développement de Marseille, Marseille, France "
Published in "Scientific Reports" (2017-02-17)

Primary sensory neurons are heterogeneous by myriad of molecular criteria. However, the functional significance of this remarkable heterogeneity is just emerging. We precedently described the GINIP(+) neurons as a new subpopulation of non peptidergic C-fibers encompassing the free nerve ending cutaneous MRGPRD(+) neurons and C-LTMRs. Using our recently generated ginip mouse model, we have been able to selectively ablate the GINIP(+) neurons and assess their functional role in the somatosensation. We found that ablation of GINIP(+) neurons affected neither the molecular contents nor the central projections of the spared neurons. GINIP-DTR mice exhibited impaired sensation to gentle mechanical stimuli applied to their hairy skin and had normal responses to noxious mechanical stimuli applied to their glabrous skin, under acute and injury-induced conditions. Importantly, loss of GINIP(+) neurons significantly altered formalin-evoked first pain and drastically suppressed the second pain response. Given that MRGPRD(+) neurons have been shown to be dispensable for formalin-evoked pain, our study suggest that C-LTMRs play a critical role in the modulation of formalin-evoked pain.

Modulation of Disulfide Dual ENKephalinase Inhibitors (DENKIs) Activity by a Transient N-protection for Pain Alleviation by Oral Route (2015)
Modulation of Disulfide Dual ENKephalinase Inhibitors (DENKIs) Activity by a Transient N-protection for Pain Alleviation by Oral Route
Poras H, Bonnard E, Fournié-Zaluski MC, Roques BP
Pharmaleads, Paris BioPark, Paris, France
Published in "Eur J Med Chem." (2015-09-18)

The endogenous opioid system, essentially constituted by two opioid receptors which are stimulated by the natural internal effectors enkephalins (Met-enkephalin and Leu-enkephalin), is present at the different sites (peripheral, spinal, central) of the control of pain. We have demonstrated that the protection of the enkephalin inactivation by the two metallopeptidases (neprilysin and neutral aminopeptidase) increases their local concentration selectively induced by pain stimuli triggering analgesic responses. With the aim of increasing the orally antinociceptive responses of the previously described disulfide DENKIs ( [Formula: see text] CH(R1)CH2-S-S-CH2-C(R2R3)CONHCH(R4)COOR5), we designed new pro-drugs, in the same chemical series, with a transient protection of the free amino group by an acyloxyalkyl carbamate, giving rise to ((CH3)2CHCO2CH(CH3)OCONHCH(R1)CH2-S-S-CH2-C(R2R3)CONHCH(R4)COOR5) pro-drugs 2a-2g. These compounds were easily prepared from their parent analogs, with a good yield. They were tested per os and shown to be highly efficient in peripherally-controlled inflammatory and neuropathic pain with long lasting effects but completely inactive in the acute centrally-controlled hot plate test, a model of pain by excess of nociception. This demonstrates that DENKIs are able to relieve pain at its source thanks to the increase of enkephalin levels.

The Nav1. 9 Channel Is a Key Determinant of Cold Pain Sensation and Cold Allodynia (2015)
The Nav1. 9 Channel Is a Key Determinant of Cold Pain Sensation and Cold Allodynia
Lolignier S, Bonnet C, Gaudioso C, Noël J, Ruel J et al.
Pharmacologie Fondamentale et Clinique de la Douleur, Clermont Université, Université d'Auvergne, Clermont-Ferrand, France;
Published in "Cell Rep. " (2015-05-19)

Cold-triggered pain is essential to avoid prolonged exposure to harmfully low temperatures. However, the molecular basis of noxious cold sensing in mammals is still not completely understood. Here, we show that the voltage-gated Nav1.9 sodium channel is important for the perception of pain in response to noxious cold. Nav1.9 activity is upregulated in a subpopulation of damage-sensing sensory neurons responding to cooling, which allows the channel to amplify subthreshold depolarizations generated by the activation of cold transducers. Consequently, cold-triggered firing is impaired in Nav1.9(-/-) neurons, and Nav1.9 mice and knockdown rats show increased cold pain thresholds. Disrupting Nav1.9 expression in rodents also alleviates cold pain hypersensitivity induced by the antineoplastic agent oxaliplatin. We conclude that Nav1.9 acts as a subthreshold amplifier in cold-sensitive nociceptive neurons and is required for the perception of cold pain under normal and pathological conditions.

The Low-Threshold Calcium Channel Cav3.2 Determines Low-Threshold Mechanoreceptor Function (2015)
The Low-Threshold Calcium Channel Cav3.2 Determines Low-Threshold Mechanoreceptor Function
Amaury François, Niklas Schüetter, Sophie Laffray, Juan Sanguesa, Anne Pizzoccaro, Stefan Dubel, Annabelle Mantilleri, Joel Nargeot, Jacques Noël, John N. Wood, Aziz Moqrich, Olaf Pongs, Emmanuel Bourinet
Institut de Génomique Fonctionnelle, Université de Montpellier, France
Published in "Cell Reports" (2015-01-20)

The T-type calcium channel Cav3.2 emerges as a key regulator of sensory functions, but its expression pattern within primary afferent neurons and its contribution to modality-specific signaling remain obscure. Here, we elucidate this issue using a unique knockin/flox mouse strain wherein Cav3.2 is replaced by a functional Cav3.2-surface-ecliptic GFP fusion. We demonstrate that Cav3.2 is a selective marker of two major low-threshold mechanoreceptors (LTMRs), A?- and C-LTMRs, innervating the most abundant skin hair follicles. The presence of Cav3.2 along LTMR-fiber trajectories is consistent with critical roles at multiple sites, setting their strong excitability. Strikingly, the C-LTMR-specific knockout uncovers that Cav3.2 regulates light-touch perception and noxious mechanical cold and chemical sensations and is essential to build up that debilitates allodynic symptoms of neuropathic pain, a mechanism thought to be entirely A-LTMR specific. Collectively, our findings support a fundamental role for Cav3.2 in touch/pain pathophysiology, validating their critic pharmacological relevance to relieve mechanical and cold allodynia.



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Temp range -2 degrees C. to 55 degrees C (in 20 to 25 degree C. ambient environment, 50% RH)
Temp accuracy +/- 0.5 degrees C.
Temperature uniformity on plate +/- 0.5 degrees C.
Power requirements 110V/220V automatic, 100W
Plate Dimensions 165 x 165 mm
Control unit dimensions 305 x 280 x 158 mm
Weight 6,650 kg

Model:
BIO-CHP
Cold Hot Plate Test (Modif.)
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