Do fish feel itchy?
The answer helps us understand how itch has evolved.
Itch is a common and uncomfortable sensation that creates a strong desire to scratch. This mechanism may have evolved so animals can remove harmful parasites or substances from themselves. Feelings like touch, pain, and itch arise when stimuli such as mechanical pressure, temperature, or chemicals activate groups of specialized neurons in the skin. This response takes place when certain proteins — or receptors — at the surface of the neurons are stimulated. For instance, TRP ion channels such as TRPA1 play an important role in both the itch and pain responses. In mammals, directly activating these channels elicits pain. Itch is felt when itch responsive receptors are activated on a distinct set of neurons, which in turn activate TRP receptors. Although these processes have been well-studied in mammals, little is known about the existence of itch sensation in other animals.
To explore this, Esancy, Condon, Feng et al. exposed zebrafish to chemicals that induce itch in mammals, and found that imiquimod, a medicine used to treat certain skin conditions, can elicit itch in fish. When this chemical was injected into the lips of a fish, the animal rubbed them against the walls of its tank, akin to scratching an itch. Further experiments showed that imiquimod directly activated the pain-sensing ion channel TRPA1. In fact, this receptor was essential to the ‘scratching’ behavior: fish genetically engineered to lack TRPA1 did not react to the drug.
Fluorescent proteins were then used to track when the neurons that carry TRPA1 were activated.This revealed that in the skin of zebrafish, there are at least two functionally distinct populations neurons that express TRPA1. One population, whose activation is associated with the animal ‘scratching’, responds even when TRPA1 receives a low level of stimulation. The other population is less sensitive: it responds only to high-intensity stimuli and is associated with a pain response such as freezing and slower movements. Further experiments in the mouse suggest that this mechanism is present in mammals as well. This coding strategy explains how pain and itch can be experienced when the same receptors are being activated.
Studying how animals like fish experience itch gives an insight into how detecting these sensations could have evolved. In turn, understanding this mechanism at the molecular and cellular levels may help find new ways to design better treatments for itch and pain disorders.
To find out more
Read the eLife research paper on which this eLife digest is based:
