22 June 2013

Squished squid, or: noci-ceph-tion

If you’re hurt, a physician doesn’t give you an IQ test to figure out how painkiller to prescribe. (“Oh, you knew the meaning of ‘lugubrious’ and solved this trigonometry question? Take another aspirin for that sprain before you go to bed.”) But this is sometimes the approach to determine if we should be worried about caring for animals like this:

This is a squid (Doryteuthis pealeii, formerly known as Loligo pealeii). It’s a cephalopod, related to cuttlefish and octopuses. Anyone who has studied cephalopods is always impressed by how clever they are, which I have documented many times on the blog before. No doubt part of the reason they have big brains is so they can coordinate all the muscles that let them control their colours, like in this video from Michael Bok:

So many people are so impressed with their braininess that, among all the millions of species of invertebrates, cephalopods are routinely singled out as deserving “special consideration” in ethical decisions about their care and use.

But, as I pointed out above, “intelligent” doesn’t necessarily line up in any meaningful way with “pain.” Pain is a hard to get a handle on, scientifically, but a first step to answering whether an animal might experience something like pain is to look for neurons that fire specifically when the tissue is damaged. Neurons tuned to damage are nociceptors.

The quest for nociceptors in the spineless has been incredibly patchy, with very few clear cases until the last decade or so. Despite the amount of interest in the brains of cephalopods, nobody had shown they had nociceptors. That’s where a new paper from Robyn Crook and colleagues come in.

Nociceptors can be tricky to detect using physiology. Their response often overlaps with the responses of other neurons. For instance, high temperatures might fire both regular thermoreceptors and nociceptors. But these two classes of neurons are still different, and convey different information to you. After all, a burn is perceived as more than just high temperature.

One of the common properties of nociceptors is that once active, they work overtime. Repeated stimulation causes greater response in the neurons. For instance, the barest touch a feather, which might have been pleasant normally, can be agony against sunburned skin. Crook and company showed very clearly that there are neurons in the fins of squid that respond to mechanical stimulation that way.

In the top trace below (“pre-crush”), you can see the spikes of sensory neurons that are responding to increasing pressure (red bars; 100 g always damaged the tissue):

After injury (“post crush”), the pressures that originally gave no spikes are responding with big spikes. Pressures that generated spikes before injury are creating even more after injury. This is one of the signs that these neurons are not just touch receptors that respond to pressure, but are nociceptors.

Another feature of nociceptors is that they often (though not always) respond to several different kinds of stimuli. In mammals, nociceptors might respond not only to a pinch, but to high temperatures (usually over 40°C) and acids. The squid nociceptors Crook and colleagues found don’t respond to high temperatures, though no word on other kinds of stimuli. Before you argue, “That makes sense, because squid are aquatic,” trout have nociceptors that are fired by high temperatures (Sneddon et al. 2003).

They also show that these nociceptive neurons become spontaneously active after injury in the whole animal. This is the first time that spontaneous activity of nociceptors has been shown in an invertebrate.

This is an important paper in the study of nociception. And these results are a reminder of the diversity of neural responses. That  high temperatures set off our nociceptors does not mean that they do the same in all other species.

Pain is what most people are interested in when they are talking about animal care concerns, but pain is not the same as nociception. Crook and colleagues are (rightfully) cautious about about what their research implies about pain:

Our findings do not directly address the speculation that cephalopods experience pain-like states(.)

These findings don’t answer the question of whether cephalopods feel pain as deeply as a mammal does. It is surely giving us some hints, though.

Full disclosure: I know first author Robyn Crook, having had her as a speaker at a symposium on nociception I co-organized.

Additional: Sea Rotmann asked about how the experiments were done. This is an excellent question. Nociception is related to pain. When you study nociception, you have to give extra thought to whether what you’re doing is needed.

The paper notes that the squid were treated the same way that vertebrates (probably fish) would be. They limited the number of animals used in live experiments, on the assumption that any effects would be large, and made injuries that were smaller than injuries the squid naturally got in their normal routines. Most of the experiments were on isolated fins removed from anaesthetized squid.

All of these say to me that Crook and company exercised due care in they way they carried out their research.


Crook RJ, Hanlon RT, Walters ET. 2013. Squid have nociceptors that display widespread long-term sensitization and spontaneous activity after bodily injury. Journal of Neuroscience 33(24): 10021-10026. DOI:

Sneddon LU, Braithwaite VA, Gentle MJ. 2003. Do fishes have nociceptors? Evidence for the evolution of a vertebrate sensory system. Proceedings of the Royal Society B: Biological Sciences 270(1520): 1115-1121.

Related posts

Do octopuses feel pain as deeply as mammals?
Tenth International Congress for Neuroethology, Day 5

Photo from here.


Dennis Francis Blewett said...

I have not seen any discussion of it, but I want to know if there are homological similarities between invertebrates and vertebrates in relation to opoid receptors and opoid-like chemicals. I have not seen any discussion on homology in relation to pain.

- Dennis F. Blewett Jr. of Rockford, Illinois

Zen Faulkes said...

Cephalopods have opiods: Opioid inhibition of dopamine release from nervous tissue of Mytilus edulis and Octopus bimaculatus.

And crustaceans do, too; see Isolation, sequence analysis, and physiological properties of enkephalins in the nervous tissue of the shore crab Carcinus maenas L.. But those opiod chemicals have many functions that don’t seem to have anything to do with pain, like reproduction: Evidence for opioid involvement in the regulation of ovarian maturation of the fiddler crab, Uca pugilator.

I'm extremely nervous about saying, “There are common chemicals, therefore pain,” though. In studies of homology, people often underestimate the potential for evolutionary diversification and functional shift in their quest for a simple “Yes or no” criterion in determining if features are homologous or not. We know there behaviours in response to noxious stimuli differ. I think you always need to be tying these things to behaviour.