Wide-Range Measurement of Thermal Preference—A Novel Method for Detecting Analgesics Reducing Thermally-Evoked Pain in Mice

Background: Wide use of oxaliplatin as an antitumor drug is limited by severe neuropathy with pharmacoresistant cold hypersensitivity as the main symptom. Novel analgesics to attenuate cold hyperalgesia and new methods to detect drug candidates are needed. Methods: We developed a method to study the...

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Main Authors: Kinga Sałat, Anna Furgała-Wojas, Michał Awtoniuk, Robert Sałat
Format: Article
Language:English
Published: MDPI AG 2021-01-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/26/3/612
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spelling doaj-e067d35c59234847bcc0a0a968260daa2021-01-26T00:02:31ZengMDPI AGMolecules1420-30492021-01-012661261210.3390/molecules26030612Wide-Range Measurement of Thermal Preference—A Novel Method for Detecting Analgesics Reducing Thermally-Evoked Pain in MiceKinga Sałat0Anna Furgała-Wojas1Michał Awtoniuk2Robert Sałat3Department of Pharmacodynamics, Chair of Pharmacodynamics, Jagiellonian University Medical College, 9 Medyczna St., 30-688 Krakow, PolandDepartment of Pharmacodynamics, Chair of Pharmacodynamics, Jagiellonian University Medical College, 9 Medyczna St., 30-688 Krakow, PolandInstitute of Mechanical Engineering, Warsaw University of Life Sciences, 164 Nowoursynowska St., 02-787 Warsaw, PolandFaculty of Electrical and Computer Engineering, Cracow University of Technology, 24 Warszawska St., 31-155 Krakow, PolandBackground: Wide use of oxaliplatin as an antitumor drug is limited by severe neuropathy with pharmacoresistant cold hypersensitivity as the main symptom. Novel analgesics to attenuate cold hyperalgesia and new methods to detect drug candidates are needed. Methods: We developed a method to study thermal preference of oxaliplatin-treated mice and assessed analgesic activity of intraperitoneal duloxetine and pregabalin used at 30 mg/kg. A prototype analgesiameter and a broad range of temperatures (0–45 °C) were used. Advanced methods of image analysis (deep learning and machine learning) enabled us to determine the effectiveness of analgesics. The loss or reversal of thermal preference of oxaliplatin-treated mice was a measure of analgesia. Results: Duloxetine selectively attenuated cold-induced pain at temperatures between 0 and 10 °C. Pregabalin-treated mice showed preference towards a colder plate of the two used at temperatures between 0 and 45 °C. Conclusion: Unlike duloxetine, pregabalin was not selective for temperatures below thermal preferendum. It influenced pain sensation at a much wider range of temperatures applied. Therefore, for the attenuation of cold hypersensitivity duloxetine seems to be a better than pregabalin therapeutic option. We propose wide-range measurements of thermal preference as a novel method for the assessment of analgesic activity in mice.https://www.mdpi.com/1420-3049/26/3/612oxaliplatinthermal preferencedeep learningimage analysiscontrolduloxetine
collection DOAJ
language English
format Article
sources DOAJ
author Kinga Sałat
Anna Furgała-Wojas
Michał Awtoniuk
Robert Sałat
spellingShingle Kinga Sałat
Anna Furgała-Wojas
Michał Awtoniuk
Robert Sałat
Wide-Range Measurement of Thermal Preference—A Novel Method for Detecting Analgesics Reducing Thermally-Evoked Pain in Mice
Molecules
oxaliplatin
thermal preference
deep learning
image analysis
control
duloxetine
author_facet Kinga Sałat
Anna Furgała-Wojas
Michał Awtoniuk
Robert Sałat
author_sort Kinga Sałat
title Wide-Range Measurement of Thermal Preference—A Novel Method for Detecting Analgesics Reducing Thermally-Evoked Pain in Mice
title_short Wide-Range Measurement of Thermal Preference—A Novel Method for Detecting Analgesics Reducing Thermally-Evoked Pain in Mice
title_full Wide-Range Measurement of Thermal Preference—A Novel Method for Detecting Analgesics Reducing Thermally-Evoked Pain in Mice
title_fullStr Wide-Range Measurement of Thermal Preference—A Novel Method for Detecting Analgesics Reducing Thermally-Evoked Pain in Mice
title_full_unstemmed Wide-Range Measurement of Thermal Preference—A Novel Method for Detecting Analgesics Reducing Thermally-Evoked Pain in Mice
title_sort wide-range measurement of thermal preference—a novel method for detecting analgesics reducing thermally-evoked pain in mice
publisher MDPI AG
series Molecules
issn 1420-3049
publishDate 2021-01-01
description Background: Wide use of oxaliplatin as an antitumor drug is limited by severe neuropathy with pharmacoresistant cold hypersensitivity as the main symptom. Novel analgesics to attenuate cold hyperalgesia and new methods to detect drug candidates are needed. Methods: We developed a method to study thermal preference of oxaliplatin-treated mice and assessed analgesic activity of intraperitoneal duloxetine and pregabalin used at 30 mg/kg. A prototype analgesiameter and a broad range of temperatures (0–45 °C) were used. Advanced methods of image analysis (deep learning and machine learning) enabled us to determine the effectiveness of analgesics. The loss or reversal of thermal preference of oxaliplatin-treated mice was a measure of analgesia. Results: Duloxetine selectively attenuated cold-induced pain at temperatures between 0 and 10 °C. Pregabalin-treated mice showed preference towards a colder plate of the two used at temperatures between 0 and 45 °C. Conclusion: Unlike duloxetine, pregabalin was not selective for temperatures below thermal preferendum. It influenced pain sensation at a much wider range of temperatures applied. Therefore, for the attenuation of cold hypersensitivity duloxetine seems to be a better than pregabalin therapeutic option. We propose wide-range measurements of thermal preference as a novel method for the assessment of analgesic activity in mice.
topic oxaliplatin
thermal preference
deep learning
image analysis
control
duloxetine
url https://www.mdpi.com/1420-3049/26/3/612
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