Nociceptor sensitization in squids.

Pain and the avoidance behaviors it induces are important survival tools for animals, keeping them away from situations that threaten their safety. When we hurt ourselves and feel pain, it is due to nociceptors, which are nerves located throughout our body, for instance in our skin or the surface of our eyes. Nociceptors can be activated mechanically (for instance when a part of skin is cut) and by hot or cold temperatures. They can also be activated by some chemicals, and you might have already experienced it if you ate a meal with chili peppers. Chili peppers induce pain because of a chemical they contain called Capsaicin, which activates nociceptors.

Squid from the Journal of Neuroscience cover

Squids, what is different about their nociceptors and ours?

From the cover of the Journal of Neuroscience, June 12th 2013.

Almost all animals have some form of nociception, but we still do not know how nociceptors in distant species such as squids compare with those in mammals. The study by Crook and colleagues that made the cover of the Journal of Neuroscience this week looks at those nociceptors1. One important property of pain receptors is sensitization. Sensitization happens when after being activated, a nociceptor becomes more responsive to future stimuli. You may have experienced this if you had a sun burn and took a bath – what normally is an acceptable temperature for a bath can be very hot and painful after a sun burn.

The figure below illustrates how fin nerves are organized in squids (see A). Any sensory input from fins in this animal passes through the fin nerves to reach the brain. The researchers used a cut of the fin that leaves the fin nerve exposed to make their experiment. Since the fin and fin nerves are surgically removed, the inputs do not actually reach the brain in the experiment. They used Frey filaments which are very thin needles that create a slightly painful sensation when applied on the skin. Those are typically used in human research on pain receptors.

Squid Fin figure

Illustration of the experiment in which the signal that would normally induce pain are recorded by an electrode applied on the fin nerve (C).

From Crook et al., 2013, Courtesy of the Journal of Neuroscience.

As you can see in the recording of the fin nerve in E, every time the experimenter activates the nociceptors with the Frey filaments, it creates a burst of activity in the fin nerve (you can see the bursts on the black line after each arrow). This burst of activity would normally be relayed to the brain. Using such recordings, it was possible for experimenters to test whether the pain receptors in the skin, in absence of a connection with the brain, can be sensitized. They looked at the response recorded from the fin nerve as mechanical stimulation was applied to the fin. Increasing stimulus strengths induced more activity in the nociceptors, but the activation was even stronger when the stimulation was preceded by other, stronger stimulation. This is what is referred to as a sensitization effect.

The study shows that the neural pathways responsible for detecting painful stimuli in squids can be sensitized peripherally, that is without interactions with the brain. Moreover, the authors have found an intriguing effect of injuries that might constitute a difference between squid nociception and mammalian nociception. The authors report that sensitization following an injury in mammals is assumed to affect nociceptors around the injury site more strongly. However in squids, they found that injuries on one fin could sensitize other non-injured sites, including the fin on the other side of the body.

Studies like this one are crucial to understand how nociceptors work and how we could potentially alleviate pain after injuries and surgeries.


1. Robyn J. Crook, Roger T. Hanlon, Edgar T. Walters (2013) Squid Have Nociceptors That Display Widespread Long-Term Sensitization and Spontaneous Activity after Bodily Injury. The Journal of Neuroscience 33:10021-10026.

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