# Identification of molecular nociceptors in Octopus vulgaris through functional characterisation in Caenorhabditis elegans

**Authors:** Eleonora Maria Pieroni, Vincent O'Connor, Lindy Holden-Dye, Pamela Imperadore, Graziano Fiorito, James Dillon

PMC · DOI: 10.1242/bio.062268 · Biology Open · 2026-02-02

## TL;DR

Researchers identified 19 genes in octopuses linked to sensing pain by comparing them to genes in a worm model.

## Contribution

A novel bioinformatic approach identified 19 octopus nociception-related genes using C. elegans functional validation.

## Key findings

- 51 nociception-related genes were predicted in Octopus vulgaris transcriptome.
- 19 genes were prioritized based on C. elegans loss-of-function experiments in a low pH avoidance test.
- TRP channels and neuropeptides emerged as key molecules in nociception.

## Abstract

Nociception, a phenomenon crucial for animal survival, deploys evolutionarily conserved molecular mechanisms. Among invertebrate species, cephalopods are of particular interest as they possess a well-developed brain speculated to be able to encode pain-like states. This has led to their inclusion in the Directive 2010/63 EU for welfare protection.

However, the molecular mechanisms of nociception in cephalopods are still poorly characterised and it is important to address this knowledge gap to better understand cephalopods' capacity to express pain states. Here we describe a bioinformatic strategy utilising conserved nociceptive genes, to identify the orthologous candidates in the Octopus vulgaris transcriptome. We identified 51 genes we predict to function in nociception. These add to the mechanosensory TRPN and the unique chemotactile receptors recently identified in octopus suckers, thus expanding the set of genes that merit further functional characterisation in cephalopods. We therefore selected 38 orthologues in Caenorhabditis elegans, a tractable experimental platform and tested loss of function mutant strains of distinct functional gene classes (e.g. osm-9, egl-3, frpr-3) in a low pH avoidance paradigm. This identified 19 nociceptive-related genes to be prioritised for further functional characterisation in O. vulgaris.

Summary: A bioinformatic strategy for nociceptors in Octopus vulgaris identified 19 candidate genes with Caenorhabditis elegans orthologues. A subset regulates C. elegans aversion highlighting TRP channels and neuropeptides as key molecules of interest.

## Linked entities

- **Genes:** nompC (no mechanoreceptor potential C) [NCBI Gene 33768], osm-9 (Ion transport domain-containing protein) [NCBI Gene 177117], egl-3 (Neuroendocrine convertase 2) [NCBI Gene 179412], frpr-3 (G-protein coupled receptors family 1 profile domain-containing protein) [NCBI Gene 182942]
- **Species:** Octopus vulgaris (taxon 6645), Caenorhabditis elegans (taxon 6239)

## Full-text entities

- **Diseases:** pain (MESH:D010146)
- **Species:** Caenorhabditis elegans (species) [taxon 6239], Octopus vulgaris (common octopus, species) [taxon 6645]

## Full text

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## Figures

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## References

189 references — full list in the complete paper: https://tomesphere.com/paper/PMC12919962/full.md

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Source: https://tomesphere.com/paper/PMC12919962