Research summary: The evolution of nociception in arthropods

By abrahamrowe, Rethink Priorities @ 2024-04-16T22:26 (+59)

This post is a short summary of A long-read draft assembly of the Chinese mantis (Mantodea: Mantidae: Tenodera sinensis) genome reveals patterns of ion channel gain and loss across Arthropoda, a peer-reviewed, open-access publication in G3: Genes | Genomes | Genetics under a CC BY license. The paper and supplemental information can be accessed here. The original paper was written by Jay Goldberg, R. Keating Godfrey, and Meghan Barrett; the research conducted in the paper was funded by Rethink Priorities as part of our research agenda on understanding the welfare of insects on farms. 

This post was written by Abraham Rowe and reviewed for accuracy by Jay Goldberg and Meghan Barrett. All information is derived from the Goldberg et al. (2024) publication unless otherwise cited, and some text from the original publication is directly adapted for this summary.

Introduction

Mantids that engage in sexually cannibalistic behaviors (e.g., where the female eats the male during copulation) are often cited as a pinnacle example of insects’ lack of pain sensation and, therefore, sentience. In their seminal paper on insect sentience, Eisemann et al.’s (1984) Do insects feel pain?—A biological view, the authors cite the fact that male mantids continue to mate while being cannibalized as a behavioral indicator of a lack of pain sensation in insects more broadly (Eisemann et al. 1984). This behavior suggests that male mantids might not even be able to sense, and thus respond reflexively to, the noxious mechanical damage that occurs during the copulatory experience. One mechanism by which animals can sense mechanical damage is through nociceptive ion channels, proteins found in their peripheral sensory neurons. At the time of Eisemann et al.’s publication, insects were not known to have nociceptive ion channels (a fact they also discuss).

It has now been determined that many arthropods (including insects) have nociceptors that perceive chemical, mechanical, and thermal injuries. Indeed, many of their nociceptive ion channels are homologous to mammalian channels (homologous, meaning that the genes for these channels were inherited from a common ancestor to both mammals and insects). However, whether mantids have these ion channels—thus presenting a challenge to the ‘peripheral sensory perception’ part of the Eisemann argument against insect pain as demonstrated by male mantid behavior—is not known. Genes can be gained and lost across species. Finding evidence of the presence or absence of these channels in the genome of a sexually cannibalistic mantid species would be an important first step to understanding the weaknesses or strengths of Eisemann et al.’s claims about how we might interpret their behavior. 

Further, by looking at the genes of arthropods across families, we can assess how nociception may have evolved in insects and possibly begin to understand why there is a variance in nociceptive ion channel expression across the arthropods. This understanding might help us identify what kinds of noxious stimuli are perceived negatively by different insect species in the future as, for instance, some other animals are known to lack certain categories of nociceptors (e.g., cold nociception is lacking in some fish species; Sneddon 2019). Additionally, gene copy number (how many copies of that gene the species has in its genome) can also play a role in the strength of their response to a noxious stimulus (Jang et al., 2023; in Drosophila melanogaster). Determining gene copy number could eventually lead us to understand the high degree of variance in response to noxious stimuli among insects. Of course, in all cases, surveying genetic data is only a first step to answering these questions; significant additional anatomical and functional studies would still be needed.

To determine the presence/absence of nociceptive ion channels in a sexually cannibalistic mantid species, the authors sequenced and assembled the Chinese mantid (Tenodera sinensis) genome. They then combined what they learned with existing research into other arthropod genomes to try to understand the evolution of nociception in these animals. They searched for genes that are known to encode for ion channels commonly associated with sensing thermally, mechanically, and/or chemically noxious stimuli. 

In their assembly of the Chinese mantid genome, the authors found that the mantids have genes that encode many nociceptive ion channels, including those that sense mechanically, thermally, and chemically noxious stimuli. Further, their survey of arthropod genomes more broadly suggests that sensing noxious or damaging stimuli is a widespread and conserved trait across the arthropod tree.

Relatedness of nociception genes

The authors looked at genes within seven families of insects that have been shown to have nociceptive function within at least one species: TRPA1, painless, NompC, trpm, Piezo, Pkd2, and pickpocket (or ppk; a group which contains three genes). They assess a total of 40 arthropod genomes—mostly insects, but also chelicerates (like mites) and decapods (like shrimp). Most insects were found to have at least one copy of six of the seven categories of genes surveyed or at least one copy of all seven. The only insect group consistently found to have less than six was the Hymenoptera (bees, ants, wasps, and sawflies). 

However, Hymenoptera are known to have evolved some of their own novel ion channels that sense noxious stimuli (Gibbons et al. 2022), and these channels were not assessed in this study. Therefore, the study should not be taken to suggest that the Hymenoptera are incapable—or less capable—of noxious stimuli-sensing, as not all possible noxious stimuli-sensing genes were captured in the study’s dataset. 

As one example, the authors looked at the gene painless (named because when it is knocked out or otherwise silenced using gene editing/expression technologies, fruit flies were found to act as though they are unable to sense some noxious stimuli and were thus now ‘painless’). The ion channel encoded by this gene has been found to be required for thermal and mechanical nociception in fruit flies, was found in all but two of the insect genomes surveyed by Goldberg et al., and was found in their Chinese mantid genome assembly.

The gene painless, alongside many other nociceptive ion channels that the authors looked for in the arthropod genomes, was also found in the genomes of multiple species reared in human industries, such as black soldier flies, yellow mealworm beetles, silkworms, honey bees, and crickets. The presence of the painless gene and other genes related to nociception across a wide number of arthropod species whose common ancestors lived hundreds of millions of years ago suggests that the presence of nociceptors may be widespread in insects and other arthropods. It is, therefore, unsurprising that these genes are also present in mantids. Further data confirming their expression in multidendritic neurons of the peripheral nervous system and their nociceptive function are still needed. However, these data suggest there may be alternate hypotheses for the cannibalistic copulatory behavior exhibited by mantids besides the lack of nociceptive sensory biology (Gibbons and Sarlak, 2022).

Implications for mantids

Eisemann et al. (1984) and others have argued that the lack of response to injury in mantids during sexual cannibalism was an indicator that they could not feel, or even sense, pain or noxious stimuli that caused damage. However, it is clear from the genetic data in this study that mantids have the genes necessary for nociception (six of the seven categories of genes known to be associated with nociception), including mechanical nociception. These genes appear throughout the insect phylogeny and are ancient and well-conserved. Further, studies of these same genes in other insects have confirmed their nociceptive function (see review of that data in Gibbons et al., 2022). These genomic data make it more plausible that hypotheses other than a lack of pain perception may play a role in the case of mantid sexual cannibalism.

Importantly, the mere presence or absence of a gene alone might not indicate nociceptive functionality or that the gene is expressed—genes are known to evolve novel functions or lose their functions as a result of mutations, deletion, and copy events which can occur across species (Li et al., 2019). However, the authors review that there is now also behavioral evidence suggesting male mantids do, in fact, try to avoid being cannibalized during mating attempts. Together, these behavioral and genetic data suggest that noxious stimuli-sensing functions may be conserved in mantid nociceptors, though further research would be needed to confirm the expression and function of these genes in multidendritic class IV neurons of the T. sinensis male mantid peripheral sensory system at the adult life stage.

Implications for farmed insects

One functional benefit of looking at genes and gene expressions to understand insect welfare is that if the presence or absence of a gene associated with a response to certain stimuli is identified, the ecological conditions on farms could be adjusted to better meet the needs of those insects. As mentioned above, some fish species appear to lack the ability (and receptors) to sense noxious cold; this could relate to appropriate rearing, stunning, or slaughter recommendations for these species down the line.

The authors looked at multiple species of farmed, or managed, arthropods, including Peneus vannamei (whiteleg shrimp), Hermetia illucens (black soldier fly), Tenebrio molitor (yellow mealworm beetle), Acheta domesticus (house cricket), Apis mellifera (Western honey bee), and the only truly domesticated farmed insect: Bombyx mori (silkworm moth) alongside its wild relative B. mandarina. Although B. mori had fewer gene copies in most of the genes assessed, they maintained at least one copy of every gene found in their wild counterpart, suggesting domestication may not result in a loss of nociception in insects—a hypothesis some may have entertained due to the possibility of relaxed selective pressures on farms compared to the wild.

In all cases, the farmed arthropod species had the vast majority of categories of nociceptive ion channels present in their genomes; in some cases, there were significant copy number expansion events (as of yet, functionally unexplained). For instance, T. molitor had 19 copies of the ppk gene category associated with sensing mechanical and chemical damage. 

The gene most frequently absent from the genomes of the farmed arthropods was Pkd2, which is known to play a role, alongside NOMPC and trpm, in cold nociception in D. melanogaster fruit flies. The frequent absence of Pkd2 may suggest that some farmed insects cannot experience noxious cold—but given the presence of NOMPC and trpm, more data would be needed to understand if Pkd2 is necessary for cold nociception in these insects or if those other two genes are sufficient. In addition, the species of interest should be studied for possible genes that replace the functionality of Pkd2 if it is found to be necessary for cold nociception (e.g., as in the case of HsTRPA and TRPA1). Interestingly, H. illucens was found to be missing any copies of the gene painless, which is known to play a role in thermal nociception. However, given a significant expansion in TRPA1 (another thermal nociceptor) copy number and data that demonstrate black soldier fly larvae respond to noxious heat (Barrett, personal communication), it is likely H. illucens still maintain thermal nociceptive functions through other means. As such, the data suggest there are no categories of typically noxious stimuli that can reasonably be expected to be non-noxious for farmed insects at this time.

Acknowledgements

This research is a project of Rethink Priorities. It was written by Abraham Rowe, summarizing work by Jay Goldberg, R. Keating Godfrey, and Meghan Barrett. Thanks to Meghan Barrett and Jay Goldberg for helpful feedback, and Maya Deutchman for copy editing. If you like our work, please consider subscribing to our newsletter. You can explore our completed public work here.

References

Eisemann, Craig H., et al. “Do insects feel pain? — A biological view.” Experientia, vol. 40, 1984, pp. 164-167, https://doi.org/10.1007/BF01963580.

Gibbons, Matilda, et al. “Chapter Three - Can insects feel pain? A review of the neural and behavioural evidence.” Advances in Insect Physiology, vol. 63, 2022, pp. 155-229, https://doi.org/10.1016/bs.aiip.2022.10.001.

Gibbons, Matilda, and Sarlak, Sajedeh. (2020) “Inhibition of pain or response to injury in invertebrates and vertebrates.” Animal Sentience, 29(34), 2020, https://doi.org/10.51291/2377-7478.1649.

Godfrey, Jay K., et al. “A long-read draft assembly of the Chinese mantis (Mantodea: Mantidae: Tenodera sinensis) genome reveals patterns of ion channel gain and loss across Arthropoda.” G3 Genes|Genomes|Genetics, 2024, https://doi.org/10.1093/g3journal/jkae062.

Jang, Wijeong, et al. “Drosophila pain sensitization and modulation unveiled by a novel pain model and analgesic drugs.” PLoS ONE, 18(2), 2023, https://doi.org/10.1371/journal.pone.0281874.

​​Li, Tianbang, et al. “Diverse sensitivities of TRPA1 from different mosquito species to thermal and chemical stimuli.” Sci Rep 9, 20200, 2019, https://doi.org/10.1038/s41598-019-56639-w.

Sneddon, Lynne U. “Evolution of nociception and pain: evidence from fish models.” Philosophical Transactions of the Royal Society B, B37420190290, 2019, http://doi.org/10.1098/rstb.2019.0290.