Involvement of GRP/GRP receptor in the ocular itch transmission mechanism clarified by Nara Women's University

A collaborative research group by Associate Professor Keiko Takanami of the Faculty of Human Life and Environmental Sciences at Nara Women's University, together with the National Institute of Genetics, Nagaoka University of Technology, and Okayama University revealed a brainstem neural mechanism of ocular itch transmission. This was achieved in a mouse conjunctivitis model by examining whether the gastrin-releasing peptide (GRP), an itch-specific molecule in the spinal sensory nervous system that transmits bodily sensations, and its receptor are involved in ocular itch transmission. The finding is expected to aid the development of treatments for intractable pruritus such as hay fever. The study results were published on November 30, 2023, in the international scientific journal Frontiers in Molecular Neuroscience.

The number of individuals with allergic conjunctivitis, including hay fever, is increasing annually. Allergic conjunctivitis manifests as intense itchiness in the eyes. Compared to itchiness on the body, the transmission mechanism of the face was unknown.

The research group focused on GRP and its receptor. They previously reported that GRP projection and GRP receptor expression are observed in the trigeminal ganglia and superficial layer of the subnucleus caudalis of the spinal trigeminal nucleus (Sp5C) in the brainstem within the trigeminal sensory system conveying facial sensation.

The current study used a murine conjunctivitis model to investigate whether the GRP/GRP receptor system in the brainstem is involved in ocular itch transmission.

Itchy eye stimulation increased eye scratching behavior in mice and activated specific neurons in the superficial layer of the Sp5C in the brainstem as well as GRP receptor neurons in this region. Moreover, the administration of GRP to the Sp5C in the brainstem provoked intense eye scratching behavior without actual exposure to itchy eye stimulation, suggesting that the eye itching was induced by the brain stimulation. Furthermore, the disabling of GRP receptor-expressing cells in the Sp5C suppressed the eye scratching behavior induced by itchy eye stimulation to some extent.

The research group previously reported that GRP and its receptor exist in the brainstem region of not only mice and rats but also eutherians and primates. Therefore, GRP and its receptor in the brainstem may be involved in ocular itch manifestation even in primates.

According to Takanami, "A neural circuit involved in the transmission of itching in the face and eyes was unknown compared to that involved in itching on the body. Because reports assessing ocular itching behavior are scarce, we investigated the conditions for scratching behavior that could be an indicator for itching. Because scratching damages the skin and mucous membranes and further worsens the itching, suppressing inflammation that may cause itching is crucial, in addition to the elucidation of the neural basis and etiology of the continuous scratching behavior."

Journal Information
Publication: frontiers
Title: Function of gastrin-releasing peptide receptors in ocular itch transmission in the mouse trigeminal sensory system
DOI: 10.3389/fnmol.2023.1280024