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.

Keywords: TRP ion channels; animal model; behavior; drug screening; invertebrate; nociception; opioids; planarians.

FIGURE 1

Common planarian representations. (A) Dorsal exterior view. aur, auricles; oc, ocelli. (B) Ventral exterior view with extruded pharynx. exc, excretory pores; ph, pharynx; mo, mouth; geni, genital pore. (C) Nervous system. cer, cerebral ganglions; tra, transversal nerve; me, pharyngal mesh of neurons; lat, lateral nerve cord; gg, lateral ganglions. (D) Gastrovascular system. ga, gastrovascular cavity; di, diverticulum; ph, pharynx; ra, posterior ramus. (E) Reproductive system, female is represented on the left and male on the right but both are present symmetrically. ov, ovary; gl, yolk glands; bu, bursa copulatrix; at, genital atrium; tes, testis; pen, penis. (F) Photos of common planaria species from our laboratory (scale: 1 mm).

FIGURE 2

Normal “gliding” and noxious “scrunching” behavior representation. (A) Typical gliding behavior of planarians. They produce mucus and glide at a constant rate on a surface using ciliated cells located on their ventral side. Gliding speed is usually about 1–5 mm/s. (B) Typical noxious “scrunching” behavior. Scrunching is a muscular gait. The head is first anchored to the surface (t1), the body contracts (t2), anchor is switched from the head to the tail (t3 to t4), then the body elongates forward (t5), and loops to the first step (t6). The frequency of one loop varies between 0.2 and 0.8 Hz depending mostly on the species (Cochet-Escartin et al., 2015). Scrunching sometimes happen in reverse order, making the worm scrunch backward for a few seconds only.