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Experimenter-free pain assessment in mice using a thermal gradient ring and functional linear models.
Aketzali Garcia1, Justin N Siemian1, Gabriel Loewinger2
1Neuronal Circuits and Behavior Section, National Institute on Drug Abuse Intramural Research Program, National Institutes of Health, Baltimore, MD, USA.
Pain Reports
|July 14, 2026
Summary
The thermal gradient ring (TGR) combined with functional linear models (FLM) offers a robust method for evaluating pain pharmacotherapies in mice. This approach accurately assesses temperature preference and identifies drug side effects for improved pain research.
Area of Science:
- Neuroscience
- Pharmacology
- Animal Behavior
Background:
- Traditional preclinical pain tests have limitations including bias and motor interference.
- Thermal gradient tests offer a more objective measure of pain and thermal preference.
- The thermal gradient ring (TGR) is a novel apparatus designed for high-resolution thermal preference assessment.
Purpose of the Study:
- To evaluate the effectiveness of the TGR for assessing pain pharmacotherapies.
- To develop a statistical framework, specifically functional linear models (FLM), for analyzing TGR data.
- To determine if the TGR-FLM combination can improve the screening of novel pain therapies.
Main Methods:
- Examined 17 treatment conditions (pronociceptive and antinociceptive) in male and female mice using the TGR.
- Analyzed behavioral data with functional linear models (FLM) for hypothesis testing of temperature preference and motor activity.
- Utilized minute-by-minute data analysis to capture temporal dynamics of treatment effects.
Main Results:
- FLM effectively captured temporal dynamics and magnitudes of treatment effects.
- Identified locomotor side effects that were not apparent in traditional averaged analyses.
- Minute-by-minute comparisons revealed distinct temporal patterns of drug effects and side effects.
Conclusions:
- The TGR-FLM combination provides a robust framework for preclinical pain research.
- This integrated approach is a valuable tool for screening novel pain therapies.
- The method enhances the accuracy and detail of pain assessment in animal models.

