Source: Okayama University (JAPAN), Public Relations Division
For immediate release: 20 December 2022
Okayama University research: Eye scratching mechanisms in rats

(Okayama, 20 December) In a study recently published in the journal Proceedings of the Royal Society B, researchers from Okayama University investigate the neurological signals behind itchy eyes in rodents and their corresponding scratching behavior.

Anyone suffering dry skin, eczema, or insect bites will know the unpleasant effects of itchy skin. While the physiological mechanisms behind itching sensations on the skin are well understood, corresponding signals for the eyes are obscure. A research group led by Associate Professor SAKAMOTO Hirotaka from Okayama University (Ushimado Marine Institute; UMI) and Associate Professor TAKANAMI Keiko from Nara Women’s University has now investigated the neural mechanisms behind itchy eyes in rodents. What’s more, the group also provides insights on the limb tactics rodents adopt to mitigate this eye trouble.

Histamine, a chemical released under allergic and inflammatory conditions, is the trigger that sets into motion itching sensations. 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 already revealed the presence of the GRP-GRPR pathway in nerves transmitting signals from the eyes to the brain, known as trigeminal ganglion (TG) nerves. Thus, this system was the main target of their study.

The researchers first studied scratching behavior in rats when their eyes were provoked with histamine drops. They found that when histamine was instilled in either the left or the right eye, the rats used the same-sided (as the troubled eye) hindfoot for scratching and soothing that eye. However, when histamine was used to trigger itchiness in both eyes together, the rats relied primarily on the right hindfoot for rubbing. The rats seemed to show a right-sided preference when it came to eye scratching.

Next, the focus moved on to biochemical pathways and the GRP-GRPR system. It was found that histamine intervention in either eye resulted in an increase in activity of GRPR-containing neurons in that side of the brainstem. It seemed likely, then, that the GRPR-containing neurons played a role in relaying itch signals from the eyes. To confirm this further, the team used a toxin to lesion these GRPR-containing neurons in the right side of the brainstems of rats. When these rats were then given histamine drops in the eyes, the incidence and duration of scratching was indeed less. A lack of active GRPR neurons resulted in diminished itch signals from their eyes.

“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…,” suggest the researchers. Besides revealing the right-sided preference animals have when using their hindlimbs, the eye scratching test used here could also be used for determining the footedness of individual rodents in future experiments. In addition, the role of the GRP-GRPR system in TG nerves revealed could be the basis for treating eye conditions that cause itchiness.

Background
Gastrin-releasing Peptide–Gastrin-releasing Peptide receptor (GRP-GRPR) pathway: GRP is a neural chemical that plays a role in transmitting signals across the nervous system. Based on the location of the nerves carrying GRP, the signals vary. Nerves carrying GRP are connected to another set of nerves which contain GRPR—a partner for the GRP molecules being transmitted. When the two connect, biochemical signals are triggered in the brain.

Trigeminal ganglion (TG) neurons from the eyes carry GRP molecules into the bottom part of the brain. A region known as the spinal trigeminal nucleus caudalis (Sp5C) in this part of the brain is found to be rich in incoming GRP-containing nerve endings. Moreover, the Sp5C is abundant in GRPR. Thus, in this study the researchers targeted GRPR neurons in the Sp5C using a toxin to observe the role of this pathway in eye itchiness.

Reference
Yukitoshi Katayama, Ayane Miura, Tatsuya Sakamoto, Keiko Takanami and Hirotaka Sakamoto. Footedness for scratching itchy eyes in rodents. Proc. R. Soc. B, 289: 20221126.
DOI：10.1098/rspb.2022.1126
https://royalsocietypublishing.org/doi/10.1098/rspb.2022.1126

Correspondence to
Associate Professor SAKAMOTO Hirotaka, Ph.D.
Ushimado Marine Institute (UMI), Graduate School of Natural
Science and Technology, Okayama University, Ushimado,
Setouchi-shi, Okayama 701-4303, Japan.
E-mail: hsakamo (a) okayama-u.ac.jp
For inquiries, please contact us by replacing (a) with the @
https://www.science.okayama-u.ac.jp/~rinkai/en/index.html

Further information
Okayama University
1-1-1 Tsushima-naka , Kita-ku , Okayama 700-8530, Japan
Public Relations Division
E-mail: www-adm(a) adm.okayama-u.ac.jp
For inquiries, please contact us by replacing (a) with the @ mark.
Website: //www.okayama-u.ac.jp/index_e.html
Okayama Univ. e-Bulletin: //www.okayama-u.ac.jp/user/kouhou/ebulletin/
We love OKAYAMA UNIVERSITY: https://www.youtube.com/watch?v=7cXlttQIk3E
Okayama University Image Movie（2020）
https://www.youtube.com/watch?v=BKRoF0tffmA
Okayama University supports the Sustainable Development Goals: https://sdgs.okayama-u.ac.jp/en/

Okayama University Medical Research Updates （OU-MRU）
The whole volume : OU-MRU (1- )
Vol.1：Innovative non-invasive ‘liquid biopsy’ method to capture circulating tumor cells from blood samples for genetic testing
Vol.2：Ensuring a cool recovery from cardiac arrest
Vol.3：Organ regeneration research leaps forward
Vol.4：Cardiac mechanosensitive integrator
Vol.5：Cell injections get to the heart of congenital defects
Vol.6：Fourth key molecule identified in bone development
Vol.7：Anticancer virus solution provides an alternative to surgery
Vol.8：Light-responsive dye stimulates sight in genetically blind patients
Vol.9：Diabetes drug helps towards immunity against cancer
Vol.10：Enzyme-inhibitors treat drug-resistant epilepsy
Vol.11：Compound-protein combination shows promise for arthritis treatment
Vol.12：Molecular features of the circadian clock system in fruit flies
Vol.13：Peptide directs artificial tissue growth
Vol.14：Simplified boron compound may treat brain tumours
Vol.15：Metamaterial absorbers for infrared inspection technologies
Vol.16：Epigenetics research traces how crickets restore lost limbs
Vol.17：Cell research shows pathway for suppressing hepatitis B virus
Vol.18：Therapeutic protein targets liver disease
Vol.19：Study links signalling protein to osteoarthritis
Vol.20：Lack of enzyme promotes fatty liver disease in thin patients
Vol.21：Combined gene transduction and light therapy targets gastric cancer
Vol.22：Medical supportive device for hemodialysis catheter puncture
Vol.23：Development of low cost oral inactivated vaccines for dysentery
Vol.24：Sticky molecules to tackle obesity and diabetes
Vol.25：Self-administered aroma foot massage may reduce symptoms of anxiety
Vol.26：Protein for preventing heart failure
Vol.27：Keeping cells in shape to fight sepsis
Vol.28：Viral-based therapy for bone cancer
Vol.29：Photoreactive compound allows protein synthesis control with light
Vol.30：Cancer stem cells’ role in tumor growth revealed
Vol.31：Prevention of RNA virus replication
Vol.32：Enzyme target for slowing bladder cancer invasion
Vol.33：Attacking tumors from the inside
Vol.34：Novel mouse model for studying pancreatic cancer
Vol.35：Potential cause of Lafora disease revealed
Vol.36：Overloading of protein localization triggers cellular defects
Vol.37：Protein dosage compensation mechanism unravelled
Vol.38：Bioengineered tooth restoration in a large mammal
Vol.39：Successful test of retinal prosthesis implanted in rats
Vol.40：Antibodies prolong seizure latency in epileptic mice
Vol.41：Inorganic biomaterials for soft-tissue adhesion
Vol.42：Potential drug for treating chronic pain with few side effects
Vol.43：Potential origin of cancer-associated cells revealed
Vol.44：Protection from plant extracts
Vol.45：Link between biological-clock disturbance and brain dysfunction uncovered
Vol.46：New method for suppressing lung cancer oncogene
Vol.47：Candidate genes for eye misalignment identified
Vol.48：Nanotechnology-based approach to cancer virotherapy
Vol.49：Cell membrane as material for bone formation
Vol.50：Iron removal as a potential cancer therapy
Vol.51：Potential of 3D nanoenvironments for experimental cancer
Vol.52：A protein found on the surface of cells plays an integral role in tumor growth and sustenance
Vol.53：Successful implantation and testing of retinal prosthesis in monkey eyes with retinal degeneration
Vol.54：Measuring ion concentration in solutions for clinical and environmental research
Vol.55：Diabetic kidney disease: new biomarkers improve the prediction of the renal prognosis
Vol.56：New device for assisting accurate hemodialysis catheter placement
Vol.57：Possible link between excess chewing muscle activity and dental disease
Vol.58：Insights into mechanisms governing the resistance to the anti-cancer medication cetuximab
Vol.59：Role of commensal flora in periodontal immune response investigated
Vol.60：Role of commensal microbiota in bone remodeling
Vol.61：Mechanical stress affects normal bone development
Vol.62：3D tissue model offers insights into treating pancreatic cancer
Vol.63：Promising biomarker for vascular disease relapse revealed
Vol.64：Inflammation in the brain enhances the side-effects of hypnotic medication
Vol.65：Game changer: How do bacteria play Tag ?
Vol.66：Is too much protein a bad thing?
Vol.67：Technology to rapidly detect cancer markers for cancer diagnosis
Vol.68：Improving the diagnosis of pancreatic cancer
Vol.69：Early gastric cancer endoscopic diagnosis system using artificial intelligence
Vol.70：Prosthetics for Retinal Stimulation
Vol.71：The nervous system can contribute to breast cancer progression
Vol.72：Synthetic compound provides fast screening for potential drugs
Vol.73：Primary intraocular lymphoma does not always spread to the central nervous system
Vol.74：Rising from the ashes—dead brain cells can be regenerated after traumatic injury
Vol.75：More than just daily supplements — herbal medicines can treat stomach disorders
Vol.76：The molecular pathogenesis of muscular dystrophy-associated cardiomyopathy
Vol.77：Green leafy vegetables contain a compound which can fight cancer cells
Vol.78：Disrupting blood supply to tumors as a new strategy to treat oral cancer
Vol.79：Novel blood-based markers to detect Alzheimer’s disease
Vol.80：A novel 3D cell culture model sheds light on the mechanisms driving fibrosis in pancreatic cancer
Vol.81：Innovative method for determining carcinogenicity of chemicals using iPS cells
Vol.82：Making memories — the workings of a neuron revealed
Vol.83：Skipping a beat — a novel method to study heart attacks
Vol.84：Friend to Foe—When Harmless Bacteria Turn Toxic
Vol.85：Promising imaging method for the early detection of dental caries
Vol.86：Plates and belts — a toolkit to prevent accidental falls during invasive vascular proceduresa
Vol.87：Therapeutic potential of stem cells for treating neurodegenerative disease
Vol.88：Nanotechnology for making cancer drugs more accessible to the brain
Vol.89：Studying Parkinson’s disease with face-recognition software
Vol.90：High levels of television exposure affect visual acuity in children
Vol.91：Meeting high demand: Increasing the efficiency of antiviral drug production in bacteria
Vol.92：Numerical modelling to assist the development of a retinal prosthesis
Vol.93：Repurposing cancer drugs: An innovative therapeutic strategy to fight bone cancer
Vol.94：A berry vine found in Asia proves useful in combating lung cancer
Vol.95：A new avenue for detecting cancer in the blood
Vol.96：Automated cell image analysis
Vol.97：Artificial intelligence helps to determine cancer invasion
Vol.98：Okayama University launches clinical trials of a jawbone regeneration therapy using human BMP-2 transgenic protein derived from Escherichia coli.
Vol.99：A rapid flow process that can convert droplets into multilayer polymeric microcapsules
Vol.100：Understanding insect leg regeneration
Vol.101：Oral tumor progression mechanism identified
Vol.102：Controlled cell death by irradiation with light
Vol.103：High-quality growth
Vol.104：The determinants of persistent and severe COVID-19 revealed
Vol.105：The dynamics of skin regeneration revealed
Vol.106：The skin electrically modelled
Vol.107：COVID-19 mRNA vaccines and fever: A possible new link
Vol.108：Track changes: A new test to study cancer progression