Anyone who suffers from dry skin, eczema or insect bites will know the unpleasant effects of itchy skin. While the physiological mechanisms behind skin itching are well understood, the corresponding signals for the eyes are unclear. A research group led by Associate Professor SAKAMOTO Hirotaka of Okayama University (Ushimado Marine Institute; UMI) and Associate Professor TAKANAMI Keiko of Nara Women’s University has now investigated the neural mechanisms behind itchy eyes in rodents. What’s more, the group offers insight into the limb tactics rodents have adopted to alleviate this eye problem.
Histamine, a chemical released in allergic and inflammatory conditions, is the trigger that activates the itching sensation. Skin-related itch signals are transmitted in neurons via a biochemical pathway known as the spinal Gastrin-releasing Peptide-Gastrin-releasing Peptide receptor (GRP-GRPR) pathway. Now, the research team has uncovered the presence of the GRP-GRPR pathway in nerves that transmit signals from the eyes to the brain, known as the trigeminal ganglion (TG) nerves. Therefore, this system was the main target of his work.
The researchers first studied the itching behavior of mice when their eyes were provoked by histamine drops. They found that when histamine was instilled in either the left or right eye, the mice used their hind foot on the same side (as the problem eye) to scratch and soothe that eye. However, when histamine was used to trigger itching in both eyes together, the mice relied primarily on the right hind foot for friction. The rats seemed to prefer the right side when it came to eye scratching.
Next, the focus shifted to biochemical pathways and the GRP-GRPR system. It was found that histamine intervention in both eyes caused an increase in the activity of GRPR-containing neurons on that side of the brain stem. It seemed likely, then, that GRPR-containing neurons were involved in the transmission of itch signals from the eyes. To further confirm this, the team used a toxin to lesion these GRPR-containing neurons on the right side of the mice’s brain stems. When these mice were given histamine drops in their eyes, the incidence and duration of itching was indeed less. The lack of active GRPR neurons resulted in reduced itch signals from their eyes.
“These findings may open a new field of research on laterality mechanisms in vertebrates and may also offer new potential therapeutic approaches,” the researchers say. In addition to revealing the right-sided preference of animals when using their hind legs, the eye-scratch test used here can also be used to determine the bipedality of individual rodents in future experiments. In addition, the role of the GRP-GRPR system in emerging TG nerves may be fundamental in the treatment of eye conditions that cause itching.
Gastrin-Releasing Peptide-Gastrin-Releasing Peptide Receptor (GRP-GRPR) Pathway: GRP is a neural chemical involved in the transmission of signals throughout the nervous system. The signals change according to the location of the nerves carrying the GRP. GRP-bearing nerves are connected to another nerve group that contains GRPR, a partner for transmitted GRP molecules. When the two combine, biochemical signals are triggered in the brain.
Trigeminal ganglion (TG) neurons from the eyes carry GRP molecules to the lower part of the brain. An area in this part of the brain known as the spinal trigeminal nucleus caudalis (Sp5C) has been found to be rich in incoming GRP-containing nerve endings. Also, Sp5C is abundant in GRPR. Therefore, in this study, the researchers targeted GRPR neurons in Sp5C using a toxin to observe the role of this pathway in eye itch.
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