Von Frey testing revisited: Provision of an online algorithm for improved accuracy of 50% thresholds.


Journal

European journal of pain (London, England)
ISSN: 1532-2149
Titre abrégé: Eur J Pain
Pays: England
ID NLM: 9801774

Informations de publication

Date de publication:
04 2020
Historique:
received: 07 10 2019
revised: 12 12 2019
accepted: 23 12 2019
pubmed: 1 1 2020
medline: 21 11 2020
entrez: 1 1 2020
Statut: ppublish

Résumé

In the pain field, it is essential to quantify nociceptive responses. The response to the application of von Frey filaments to the skin measures tactile sensitivity and is a surrogate marker of allodynia in states of peripheral and/or central sensitization. The method is widely used across species within the pain field. However, uncertainties appear to exist regarding the appropriate method for analysing obtained data. Therefore, there is a need for refinement of the calculations for transformation of raw data to quantifiable data. Here, we briefly review the fundamentals behind von Frey testing using the standard up-down method and the associated statistics and show how different parameters of the statistical equation influence the calculated 50% threshold results. We discuss how to obtain the most accurate estimations in a given experimental setting. To enhance accuracy and reproducibility across laboratories, we present an easy to use algorithm that calculates 50% thresholds based on the exact filaments and their interval using math beyond the traditional methods. This tool is available to the everyday user of von Frey filaments and allows the insertion of all imaginable ranges of filaments and is thus applicable to data derived in any species. We advocate for the use of this algorithm to minimize inaccuracies and to improve internal and external reproducibility. The von Frey testing procedure is standard for assessing peripheral and central sensitization but is associated with inaccuracies and lack of transparency in the associated math. Here, we describe these problems and present a novel statistical algorithm that calculates the exact thresholds using math beyond the traditional methods. The online platform is transparent, free of charge and easy to use also for the everyday user of von Frey filaments. Application of this resource will ultimately reduce errors due to methodological misinterpretations and increase reproducibility across laboratories.

Sections du résumé

BACKGROUND
In the pain field, it is essential to quantify nociceptive responses. The response to the application of von Frey filaments to the skin measures tactile sensitivity and is a surrogate marker of allodynia in states of peripheral and/or central sensitization. The method is widely used across species within the pain field. However, uncertainties appear to exist regarding the appropriate method for analysing obtained data. Therefore, there is a need for refinement of the calculations for transformation of raw data to quantifiable data.
METHODS
Here, we briefly review the fundamentals behind von Frey testing using the standard up-down method and the associated statistics and show how different parameters of the statistical equation influence the calculated 50% threshold results. We discuss how to obtain the most accurate estimations in a given experimental setting.
RESULTS
To enhance accuracy and reproducibility across laboratories, we present an easy to use algorithm that calculates 50% thresholds based on the exact filaments and their interval using math beyond the traditional methods. This tool is available to the everyday user of von Frey filaments and allows the insertion of all imaginable ranges of filaments and is thus applicable to data derived in any species.
CONCLUSION
We advocate for the use of this algorithm to minimize inaccuracies and to improve internal and external reproducibility.
SIGNIFICANCE
The von Frey testing procedure is standard for assessing peripheral and central sensitization but is associated with inaccuracies and lack of transparency in the associated math. Here, we describe these problems and present a novel statistical algorithm that calculates the exact thresholds using math beyond the traditional methods. The online platform is transparent, free of charge and easy to use also for the everyday user of von Frey filaments. Application of this resource will ultimately reduce errors due to methodological misinterpretations and increase reproducibility across laboratories.

Identifiants

pubmed: 31889375
doi: 10.1002/ejp.1528
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

783-790

Informations de copyright

© 2019 European Pain Federation - EFIC®.

Références

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Bonin, R. P., Bories, C., & De Koninck, Y. (2014). A simplified up-down method (SUDO) for measuring mechanical nociception in rodents using von Frey filaments. Molecular Pain, 10, 26. https://doi.org/10.1186/1744-8069-10-26
Bradman, M. J. G., Ferrini, F., Salio, C., & Merighi, A. (2015). Practical mechanical threshold estimation in rodents using von Frey hairs/Semmes-Weinstein monofilaments: Towards a rational method. Journal of Neuroscience Methods, 255, 92-103. https://doi.org/10.1016/j.jneumeth.2015.08.010
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Chaplan, S. R., Bach, F. W., Pogrel, J. W., Chung, J. M., & Yaksh, T. L. (1994). Quantitative assessment of tactile allodynia in the rat paw. Journal of Neuroscience Methods, 53(1), 55-63. https://doi.org/10.1016/0165-0270(94)90144-9
Detloff, M. R., Clark, L. M., Hutchinson, K. J., Kloos, A. D., Fisher, L. C., & Basso, D. M. (2010). Validity of acute and chronic tactile sensory testing after spinal cord injury in rats. Experimental Neurology, 225(2), 366-376. https://doi.org/10.1016/j.expneurol.2010.07.009
Dixon, W. J. (1965). The Up-and-Down Method for Small Samples. Journal of the American Statistical Association, 60(312), 967-978. https://doi.org/10.1080/01621459.1965.10480843
Dixon, W. J. (1980). Efficient Analysis of Experimental Observations. Annual Review of Pharmacology and Toxicology, 20(1), 441-462. https://doi.org/10.1146/annurev.pa.20.040180.002301
Gonzalez-Cano, R., Boivin, B., Bullock, D., Cornelissen, L., Andrews, N., & Costigan, M. (2018). Up-down reader: An Open Source Program for Efficiently Processing 50% von Frey Thresholds. Frontiers in Pharmacology, 9, https://doi.org/10.3389/fphar.2018.00433
Milligan, E. D., Mehmert, K. K., Hinde, J. L., Harvey, L. O., Martin, D., Tracey, K. J., … Watkins, L. R. (2000). Thermal hyperalgesia and mechanical allodynia produced by intrathecal administration of the human immunodeficiency virus-1 (HIV-1) envelope glycoprotein, gp120. Brain Research, 861(1), 105-116. https://doi.org/10.1016/S0006-8993(00)02050-3
Mills, C., LeBlond, D., Joshi, S., Zhu, C., Hsieh, G., Jacobson, P., … Decker, M. (2012). Estimating efficacy and drug ED50’s using von Frey thresholds: Impact of weber’s law and log transformation. The Journal of Pain: Official Journal of the American Pain Society, 13(6), 519-523. https://doi.org/10.1016/j.jpain.2012.02.009
Werner, M. U., Rotbøll-Nielsen, P., & Ellehuus-Hilmersson, C. (2011). Humidity affects the performance of von Frey monofilaments. Acta Anaesthesiologica Scandinavica, 55(5), 577-582. https://doi.org/10.1111/j.1399-6576.2011.02426.x

Auteurs

Sarah Louise Christensen (SL)

Danish Headache Center, Glostrup Research Institute, Rigshospitalet Glostrup, Denmark.

Rie Bager Hansen (RB)

Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark.

Mikkel Ammentorp Storm (MA)

Danish Headache Center, Glostrup Research Institute, Rigshospitalet Glostrup, Denmark.

Jes Olesen (J)

Danish Headache Center, Glostrup Research Institute, Rigshospitalet Glostrup, Denmark.

Thomas Folkmann Hansen (TF)

Danish Headache Center, Glostrup Research Institute, Rigshospitalet Glostrup, Denmark.

Michael Ossipov (M)

Syneos Health, Raleigh, NC, USA.
Department of Pharmacology, College of Medicine, University of Arizona Health Sciences Center, Tucson, AZ, United States.

Jose M G Izarzugaza (JMG)

Department of Bio and Health Informatics, Technical University of Denmark, Kongens Lyngby, Denmark.

Frank Porreca (F)

Department of Pharmacology, College of Medicine, University of Arizona Health Sciences Center, Tucson, AZ, United States.

David M Kristensen (DM)

Danish Headache Center, Glostrup Research Institute, Rigshospitalet Glostrup, Denmark.
University of Rennes, Inserm, EHESP, Irset (Institut de Recherche en Santé, Environnement et Travail) - UMR_S 1085, Rennes, France.

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