Characterization of the expression of gastrin‐releasing peptide and its receptor in the trigeminal and spinal somatosensory systems of Japanese macaque monkeys: Insight into humans

Abstract

Gastrin‐releasing peptide (GRP) and its receptor (GRPR) have been identified as itch mediators in the spinal and trigeminal somatosensory systems in rodents. In primates, there are few reports of GRP/GRPR expression or function in the spinal sensory system and virtually nothing is known in the trigeminal system. The aim of the present study was to characterize GRP and GRPR in the trigeminal and spinal somatosensory system of Japanese macaque monkeys (Macaca fuscata). cDNA encoding GRP was isolated from the macaque dorsal root ganglion (DRG) and exhibited an amino acid sequence that was highly conserved among mammals and especially in primates. Immunohistochemical analysis demonstrated that GRP was expressed mainly in the small‐sized trigeminal ganglion and DRG in adult macaque monkeys. Densely stained GRP‐immunoreactive (ir) fibers were observed in superficial layers of the spinal trigeminal nucleus caudalis (Sp5C) and the spinal cord. In contrast, GRP‐ir fibers were rarely observed in the principal sensory trigeminal nucleus and oral and interpolar divisions of the spinal trigeminal nucleus. cDNA cloning, in situ hybridization, and Western blot revealed substantial expression of GRPR mRNA and GRPR protein in the macaque spinal dorsal horn and Sp5C. Our Western ligand blot and ligand derivative stain for GRPR revealed that GRP directly bound in the macaque Sp5C and spinal dorsal horn as reported in rodents. Finally, GRP‐ir fibers were also detected in the human spinal dorsal horn. The spinal and trigeminal itch neural circuits labeled with GRP and GRPR appear to function also in primates.

Footedness for scratching itchy eyes in rodents

“…Somatosensation from the eyes is conveyed to the brain by trigeminal ganglion (TG) neurons, which terminate in the trigeminal sensory nuclei of the medulla oblongata. We have shown that one of the trigeminal sensory nuclei, the spinal trigeminal nucleus caudalis (Sp5C), contains gastrin-releasing peptide (GRP)-immunoreactive (ir) fibres of TG neurons and that the GRP receptor (GRPR) is localized to Sp5C in Asian musk shrews (Suncus murinus), mice, rats and macaque monkeys [17][18][19][20]. Because the GRP-GRPR system in the spinal somatosensory system contributes to itch sensation from the body region in mice [21][22][23][24][25][26], we hypothesize that the trigeminal GRP-GRPR system is involved in the transmission of itch from the eyes.…”

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

“…Immunofluorescence for c-Fos and beta-galactosidase (β-gal), an indicator of Grpr expression was conducted according to our previously described methods ( Takanami et al, 2022 ). Non-specific binding components were blocked with 1% normal donkey serum and 1% bovine serum albumin in PBS containing 0.3% Triton X-100 for 1 h at room temperature.…”

“…In the spinal sensory system, gastrin-releasing peptide (GRP) and GRP receptor (GRPR) expressed in the spinal dorsal horn have been reported to specifically transmit acute and chronic itch, based on experiments using mice ( Sun and Chen, 2007 ; Sun et al, 2009 ; Zhao et al, 2013 ; Akiyama et al, 2014 ; Barry et al, 2020 ; Kiguchi et al, 2020 ; Kanehisa et al, 2022 ). In the trigeminal sensory system, we previously reported that GRP is expressed in the trigeminal ganglia and GRPR is specifically expressed in the superficial layer of the caudal part of the spinal trigeminal nucleus (Sp5C) in mice, rats, Suncus, and monkeys ( Takanami et al, 2014 , 2016 , 2022 ). However, whether GRPR in Sp5C is actually involved in the transmission of facial itching is unclear.…”

A non-canonical retina-ipRGCs-SCN-PVT visual pathway for mediating contagious itch behavior

“…Gastrin-releasing peptide (GRP) in somatosensory neurons encodes itch-specific information and can activate GRPR, a G q protein-coupled receptor (GPCR), in the spinal cord to transmit itch information in mice ( Barry et al, 2020 ; Chen, 2021 ; Sun and Chen, 2007 ; Sun et al, 2009 ). GRP is conserved across animal phyla, including mammals ( Hirooka et al, 2021 ; Takanami et al, 2022 ). Suprachiasmatic nucleus (SCN) GRP neurons are a subset of retinorecipient cells located in the ventrolateral side (the core area) and convey photic information directly from the retinohypothalamic tract (RHT) ( Abrahamson and Moore, 2001 ; Karatsoreos et al, 2004 ).…”