Validation

Mechanical: External Validation against filaments

Click here for Topcat’s bibliography, with MouseMet, RatMet and our Thermal Probe listed first.

The initial validation of MouseMet was carried out at the Comparative Biology Centre, Newcastle University and the data presented at the autumn meeting of the AVA in Liverpool 2011.
The key findings were:

  • The MouseMet data showed less variability than the filaments
  • The operators observed that MouseMet was easier to use than the filaments
  • Although the mean thresholds recorded with filaments were not significantly lower post-operatively, those recorded with MouseMet did show a significant decrease (although there was no significant analgesic effect).
    Click here for the poster.

Two more validation studies of MouseMet were then carried out at  the Department of Medical Science, Bristol University and the data presented at an NC3Rs meeting in October 2012.
The key findings were:

  • MouseMet was “faster and more comfortable to use” than the filaments.
  • Both the filaments and Mousemet measured a significant decrease in threshold post-operatively.
    Click here for the poster.

RatMet operates on the same principle as MouseMet but with a force range of 1-80g. Click here for a poster presented at the AVA describing its validation at the Comparative Biology Centre, Newcastle University, here for one presented at LAVA 2013, describing the validation of both MouseMet and RatMet and here for a poster at AALAS 2015, validating RatMet.

Research Publications:

Published in Pain:

Deuis JR et al (2013) An animal model of oxaliplatin-induced cold allodynia reveals a crucial role for Nav1.6 in peripheral pain pathways. http://dx.doi.org/10.1016/j.pain.2013.05.032 Epub 2013 May 24.

Published in Neuro-Oncology

Deuis JR et al (2014): Analgesic effects of clinically used compounds in novel mouse models of polyneuropathy induced by oxaliplatin and cisplatin. http://dx.doi.org/10.1093/neuonc/nou048 Epub 2014 April 8

Published in ACS Chemical Neuroscience

Deuis JR et al (2015): Activation of κ Opioid Receptors in Cutaneous Nerve Endings by Conorphin-1, a Novel Subtype-Selective Conopeptide, Does Not Mediate Peripheral Analgesia. http://pubs.acs.org/doi/abs/10.1021/acschemneuro.5b00113 Epub 2015 Aug 12

Mechanical: Internal Validation

Any new electronic von Frey system will be validated against von Frey filaments because they are the accepted standard. They have, however, been described (Bove et al, 2008) as a “tin standard”, (rather than a gold one). As part of our own validation of MouseMet, we have investigated two aspects of the filament method which we believe will lead to differences in data when compared with an electronic system (even a perfect one)

1.The diameter of filaments varies with their rated force

It is well accepted that mechanical threshold is linearly related to the diameter of the probe. EVF systems (including MouseMet and RatMet) have a probe of constant diameter, irrespective of the force that they apply. We investigated mathematically the likely effect of this difference on the data. Click here for a PDF summarising the conclusion.

2. The up-down method

Filament data requires post test analysis to derive a mechanical threshold force. This is usually performed using the up-down method (or sometimes the % response method). We therefore built a mathematical simulation of the up-down method. This required an estimate of the likely standard deviation of baseline threshold data from mice which was gained from three sites currently using MouseMet. This simulator was then used to investigate the discrete nature of the data derived from the up-down method and to evaluate the likely errors if the method is used incorrectly. It was presented as a poster abstract at the spring meeting of the AVA, Nottingham 2014. Click here for the poster.

The thermal probe

Published in Temperature

DeuisJ and Vetter I (2016) The thermal probe test: A novel behavioral assay to quantify thermal paw withdrawal thresholds in mice. Temperature, Vol 3, Iss 2. DOI: 10.1080/23328940.2016.1157668

The initial baseline data are tight, with baselines at approximately 50C. Heat allodynia has been detected by significant reduction of threshold and analgesia by an increase. The findings are in line with Topcat’s extensive database of data from thermal testing with our probes on other species. To arrange an early trial, please email mike@topcatmetrology.co.uk.

3Rs

MouseMet makes a considerable contribution to the 3Rs: animal welfare is improved by less handling and acclimation times as there is no need to move the rodents to a different cage for thermal testing. Click here for a poster presented at the Society of Experimental Biology’s recent meeting on the 3Rs and click here for a pdf summarising MouseMet’s contribution to the 3Rs.