Stereotypical escape behavior in Caenorhabditis elegans allows quantification of nociceptive stimuli levels

TL;DR

This study develops a quantitative model to objectively measure thermal nociception in C. elegans, enabling assessment of analgesic effects and genetic mutations through stereotyped escape behaviors.

Contribution

The paper introduces a novel model linking worm escape behavior to perceived nociceptive stimulus levels, facilitating quantitative pain assessment in animal models.

Findings

Ibuprofen reduces perceived thermal nociception in worms.

TRPV mutant alters worm behavior beyond nociception effects.

Minimal worm sample size for significant analgesic detection identified.

Abstract

Experiments of pain with human subjects are difficult, subjective, and ethically constrained. Since the molecular mechanisms of pain transduction are reasonably conserved among different species, these problems are partially solved by the use of animal models. However, animals cannot easily communicate to us their own pain levels. Thus progress depends crucially on our ability to quantitatively and objectively infer the perceived level of noxious stimuli from the behavior of animals. Here we develop a quantitative model to infer the perceived level of thermal nociception from the stereotyped nociceptive response of individual nematodes Caenorhabditis elegans stimulated by an IR laser. The model provides a method for quantification of analgesic effects of chemical stimuli or genetic mutations in C. elegans. We test the nociception of ibuprofen-treated worms and a TRPV (transient receptor potential) mutant, and we show that the perception of thermal nociception for the ibuprofen treated worms is lower than the wild-type. At the same time, our model shows that the mutant changes the worm's behavior beyond affecting nociception. Finally, we determine the stimulus level that best distinguishes the analgesic effects and the minimum number of worms that allow for a statistically significant identification of these effects.