Footedness for scratching itchy eyes in rodents

Abstract

The neural bases of itchy eye transmission remain unclear compared with those involved in body itch. Here, we show in rodents that the gastrin-releasing peptide receptor (GRPR) of the trigeminal sensory system is involved in the transmission of itchy eyes. Interestingly, we further demonstrate a difference in scratching behaviour between the left and right hindfeet in rodents; histamine instillation into the conjunctival sac of both eyes revealed right-foot biased laterality in the scratching movements. Unilateral histamine instillation specifically induced neural activation in the ipsilateral sensory pathway, with no significant difference between the activations following left- and right-eye instillations. Thus, the behavioural laterality is presumably due to right-foot preference in rodents. Genetically modified rats with specific depletion of Grpr- expressing neurons in the trigeminal sensory nucleus caudalis of the medulla oblongata exhibited fewer and shorter histamine-induced scratching movements than controls and eliminated the footedness. These results taken together indicate that the Grpr -expressing neurons are required for the transmission of itch sensation from the eyes, but that foot preference is generated centrally. These findings could open up a new field of research on the mechanisms of the laterality in vertebrates and also offer new potential therapeutic approaches to refractory pruritic eye disorders.

Function of gastrin-releasing peptide receptors in ocular itch transmission in the mouse trigeminal sensory system

“…Mature mice aged 10 weeks or older were used in all behavioral analyses. Itch behavior was assessed according to a previously described method ( Katayama et al, 2022 ). All the mice were housed individually for at least 1 week prior to the behavioral analysis.…”

“… Nakano et al (2009) analyzed His-induced eye scratching behavior in mice and found that eye scratching behavior includes an uninterrupted cluster of rapid fore- or hind-limb movements directed to the ocular surface. We also observed His-induced eye scratching behavior in rats and mice ( Katayama et al, 2022 ); however, how non-histaminergic pruritogens act on itchy eyes is unclear.…”

“…However, whether GRPR in Sp5C is actually involved in the transmission of facial itching is unclear. Although we previously reported that GRPR-expressing neurons in the Sp5C of rats transmit histamine (His)-induced itchy eyes ( Katayama et al, 2022 ), whether GRPR is involved in the transmission of itchy eyes in the trigeminal sensory system in mice remains unclear.…”

Neuropeptidergic control circuits in the spinal cord for male sexual behaviour: Oxytocin–gastrin‐releasing peptide systems

“…GRPR‐expressing neurons in the lateral amygdala are known as GABAergic neurons and are involved in conditioned fear responses 11 . GRPR‐expressing neurons in the spinal dorsal horn and trigeminal sensory nuclei of the brainstem have been reported to be involved in itch transmission, which is completely separated from pain transmission at the spinal cord and brainstem levels 29,35,36 . Furthermore, it has long been reported that the GRP system acts significantly and play an important role in feeding behaviour 3–5,28 .…”

“…11 GRPRexpressing neurons in the spinal dorsal horn and trigeminal sensory nuclei of the brainstem have been reported to be involved in itch transmission, which is completely separated from pain transmission at the spinal cord and brainstem levels. 29,35,36 Furthermore, it has long been reported that the GRP system acts significantly and play an important role in feeding behaviour. [3][4][5]28 In addition to actions in the nervous system, it has been reported that high expression of GRPR promotes not only carcinogenesis and proliferation in prostate cancer 37 but also insulin secretion in pancreatic islet cells.…”