Planarian nociception: Lessons from a scrunching flatworm

Abstract

In addition to being studied for their exceptional regeneration abilities, planarians (i.e., flatworms) have also been extensively used in the context of pharmacological experiments during the past century. Many researchers used planarians as a model system for the study of drug abuse because they display high similarities with the nervous system of vertebrates at cellular and molecular levels (e.g., neuronal morphology, neurotransmitter ligands, and receptor function). This research field recently led to the discovery of causal relationships between the expression of Transient Receptor Potential ion channels in planarians and their behavioral responses to noxious stimuli such as heat, cold or pharmacological analogs such as TRP agonists, among others. It has also been shown that some antinociceptive drugs modulate these behaviors. However, among the few authors that tried to implement a full behavior analysis, none reached a consensual use of the terms used to describe planarian gaits yet, nor did they establish a comprehensive description of a potential planarian nociceptive system. The aim of this review is therefore to aggregate the ancient and the most recent evidence for a true nociceptive behavior in planarians. It also highlights the convenience and relevance of this invertebrate model for nociceptive tests and suggests further lines of research. In regards to past pharmacological studies, this review finally discusses the opportunities given by the model to extensively screen for novel antinociceptive drugs.

Behavioral and pharmacological characterization of planarian nociception

“…In order to justify the use of planarians as a nociception model, we should be able to modulate their reactions to judge the efficacy of a drug of interest. Here, we focused on commonly used antinociceptives, such as the gold standard pain killer morphine ( Paul et al, 2021 ), which had already been used multiple times over the last few decades to modulate planarian behavior ( Reho et al, 2022 ). In our study, the observed lack of antinociceptive properties of morphine when co-administered with high concentrations of AITC was not surprising.…”

“…Unfortunately, even though planarian behavior has been described for centuries, only a few scarce studies observing nociceptive behaviors can be found. Moreover, these few studies only described nociceptive behavior by how they look like, without properly characterizing and quantifying any specific gait, thus leading to various interpretations and unclear definitions ( Reho et al, 2022 ). One particular tipping point of this research field is a study by Cochet-Escartin et al from 2015 that meticulously characterized one of the nociceptive gaits observed in planarians called ‘scrunching’ ( Cochet-Escartin et al, 2015 ).…”

“…Scrunching is opposed to the normal smooth ‘gliding’ gait of planarians, which is a continuous beating of ciliated cells present on the ventral side of the animals, and helped by continuous production of mucus from rhabdite cells ( Rompolas et al, 2013 ). Besides scrunching, other nociceptive gaits have been exploited in former studies – such as ‘C-shapes’ or ‘Corkscrew’ – but none are sufficiently well characterized to be consensually used ( Reho et al, 2022 ). It has to be noted that these other gaits often appear altogether in a relatively chaotic fashion, with no clear distinctions between one or the other, and are often described all together as ‘seizure-like activity’ ( Reho et al, 2022 ).…”

“…Besides scrunching, other nociceptive gaits have been exploited in former studies – such as ‘C-shapes’ or ‘Corkscrew’ – but none are sufficiently well characterized to be consensually used ( Reho et al, 2022 ). It has to be noted that these other gaits often appear altogether in a relatively chaotic fashion, with no clear distinctions between one or the other, and are often described all together as ‘seizure-like activity’ ( Reho et al, 2022 ). On the other hand, these definitions issues did not hinder new research on nociceptive planarian behavior to emerge with alternative types of tests, such as thermotaxis or thigmotaxis ( Inoue et al, 2015 ).…”