Takanami K, Kuroiwa M, Ishikawa R, Imai Y, Oishi A, Hashino M, Shimoda Y, Sakamoto H, Koide T (2023) Function of gastrin-releasing peptide receptors in ocular itch transmission in the mouse trigeminal sensory system. Front Mol Neurosci 16:1280024. doi: 10.3389/fnmol.2023.1280024 PMID: 38098939

Objective: To investigate the role of gastrin-releasing peptide (GRP) and GRP receptor (GRPR) in itch transmission in the spinal somatosensory system, and to determine whether the GRP system is involved in itch neurotransmission of the eyes in the trigeminal sensory system

Summary: Administering itch mediators like histamine (His) and chloroquine (CQ) caused high levels of eye scratching in a concentration-dependent manner, with significant gender differences observed for His. Histological studies showed that His and CQ significantly activated GRPR-expressing neurons in a specific brain region of transgenic mice. Blocking these neurons with a GRPR antagonist or eliminating them reduced CQ-induced scratching. Injecting a GRPR agonist without an itch stimulus led to excessive facial scratching, indicating the central role of GRPR neurons in mediating itch responses.

Usage: 500 ng Blank-SAP (IT-21) or 500 ng Bombesin-SAP (IT-40) were intracisternally administered (5-uL volume) 2 weeks prior to behavioral experiments.

Related Products: Bombesin-SAP (Cat. #IT-40), Blank-SAP (Cat. #IT-21)

Kunimura K, Fukui Y (2021) The molecular basis for IL-31 production and IL-31-mediated itch transmission: from biology to drug development. Int Immunol 33(12):731-736. doi: 10.1093/intimm/dxab065

Objective: To investigate the molecular mechanisms of how IL-31 is produced in helper T cells upon stimulation and transmits the itch sensation to the brain.

Summary: This review highlights recent findings that show the functional significance of endothelial PAS domain 1 (EPAS1) and neurokinin B (NKB) in the IL-31-induced itch sensation.

Usage: Neurons expressing the Nppb receptor were specifically ablated by intrathecal injection of Nppb-SAP. Treatment with Bombesin-SAP reduced IL-31-induced scratching.

See: Sakata D et al. Selective role of neurokinin B in IL-31–induced itch response in mice. J Allergy Clin Immunol 144(4):1130-1133, 2019.

Related Products: Bombesin-SAP (Cat. #IT-40), Nppb-SAP (Cat. #IT-69)

Chen ZF (2021) A neuropeptide code for itch. Nat Rev Neurosci 22(12):758-776. doi: 10.1038/s41583-021-00526-9

Related Products: Bombesin-SAP (Cat. #IT-40)

Liu X, Wang Y, Tao T, Zeng L, Wang D, Wen Y, Li Y, Zhao Z, Tao A (2021) GRPR/extracellular signal-regulated kinase and NPRA/extracellular signal-regulated kinase signaling pathways play a critical role in spinal transmission of chronic itch. J Invest Dermatol 141(4):863-873. doi: 10.1016/j.jid.2020.09.008

Summary: This study investigates whether there are certain key signaling molecules downstream of the recently identified peptides mediating itch in the spinal cord. Bombesin-SAP completely abolished extracellular signal-regulated kinase (ERK) activation. ERK was the most highly activated by their agonists BNP (Nppb, brain-derived natriuretic peptide) and octreotide. Nppb-SAP only partially reduced pERK in cervical spinal cord.

Related Products: Bombesin-SAP (Cat. #IT-40), Nppb-SAP (Cat. #IT-69)

Wang Z, Jiang C, Yao H, Chen O, Rahman S, Gu Y, Zhao J, Huh Y, Ji RR (2021) Central opioid receptors mediate morphine-induced itch and chronic itch via disinhibition. Brain 144(2):665-681. doi: 10.1093/brain/awaa430

Summary: Itch is a common side effect of opioids, particularly as a result of epidural or intrathecal administration. Notably, morphine-elicited itch was suppressed by intrathecal administration of NPY and abolished by spinal ablation of GRPR+ neurons with intrathecal injection of Bombesin-SAP.

Usage: For ablation of GRPR+ neurons, mice were given an intrathecal injection of 400 ng Bombesin-SAP or Blank-SAP (control) 10 days before behavioral testing.

Related Products: Bombesin-SAP (Cat. #IT-40), Blank-SAP (Cat. #IT-21)

Liu X, Wang D, Wen Y, Zeng L, Li Y, Tao T, Zhao Z, Tao A (2020) Spinal GRPR and NPRA contribute to chronic itch in a murine model of allergic contact dermatitis. J Invest Dermatol 140(9):1856-1866.e7. doi: 10.1016/j.jid.2020.01.016

Objective: The authors investigated the peripheral and spinal mechanisms responsible for prolonged itch in a mouse model of allergic contact dermatitis (ACD) induced by squaric acid dibutylester (SADBE).

Summary: Targeting gastrin-releasing peptide receptor (GRPR) and natriuretic peptide receptor A (NPRA) may provide effective treatments for ACD associated chronic pruritus.

Usage: A single dose of Bombesin-SAP (400 ng) and Blank-SAP (400 ng) or two doses of Nppb-SAP (BNP-SAP; 650 ng) and Blank-SAP (650 ng) were administered via intrathecal injection.

Related Products: Bombesin-SAP (Cat. #IT-40), Nppb-SAP (Cat. #IT-69), Blank-SAP (Cat. #IT-21)

Kiguchi N, Uta D, Ding H, Uchida H, Saika F, Matsuzaki S, Fukazawa Y, Abe M, Sakimura K, Ko MC, Kishioka S (2020) GRP receptor and AMPA receptor cooperatively regulate itch-responsive neurons in the spinal dorsal horn. Neuropharmacology 170:108025. doi: 10.1016/j.neuropharm.2020.108025

Objective: To investigate the mechanisms for the activation of itch-responsive GRPR+ neurons in the spinal dorsal horn (SDH).

Summary: These findings demonstrate that GRP and glutamate cooperatively regulate GRPR+ AMPAR+ neurons in SDH, mediating itch sensation. GRP–GRPR and the glutamate–AMPAR system may play pivotal roles in the spinal transmission of itch in rodents and nonhuman primates.

Usage: Bombesin-SAP and Blank-SAP were administered i.t. (5 μg/5 μl).

Related Products: Bombesin-SAP (Cat. #IT-40), Blank-SAP (Cat. #IT-21)

Barry DM, Liu XT, Liu B, Liu XY, Gao F, Zeng X, Liu J, Yang Q, Wilhelm S, Yin J, Tao A, Chen ZF (2020) Exploration of sensory and spinal neurons expressing gastrin-releasing peptide in itch and pain related behaviors. Nat Commun 11(1):1397. doi: 10.1038/s41467-020-15230-y

Objective: To determine the role of GRP in sensory neurons.

Summary: GRP is a neuropeptide in sensory neurons for nonhistaminergic itch, and GRP sensory neurons are dedicated to itch transmission.

Usage: Bombesin-SAP (200 ng/5 μL, i.t.) was injected 2 weeks prior to optical stimulation.

Related Products: Bombesin-SAP (Cat. #IT-40)

Liu X, Miao XH, Liu T (2020) More than scratching the surface: recent progress in brain mechanisms underlying itch and scratch. Neurosci Bull 36(1):85-88. doi: 10.1007/s12264-019-00352-1

Summary: The discovery of descending neural circuitry to drive the itch-scratching cycle may provide potential therapeutic targets in the central nervous system for the management of chronic itch.

Usage: To ablate the spinal GRPR+ neurons, mice were intrathecally injected with Bombesin-SAP or Blank-SAP (400 ng/5 mL).

See: Gao ZR et al. Tac1-Expressing Neurons in the Periaqueductal Gray Facilitate the Itch-Scratching Cycle via Descending Regulation. Neuron 101(1):45-59.e9, 2019.

Related Products: Bombesin-SAP (Cat. #IT-40)

Pan H, Fatima M, Li A, Lee H, Cai W, Horwitz L, Hor CC, Zaher N, Cin M, Slade H, Huang T, Xu XZS, Duan B (2019) Identification of a spinal circuit for mechanical and persistent spontaneous itch. Neuron 103(6):1135-1149.e6. doi: 10.1016/j.neuron.2019.06.016

Objective: To identify a spinal circuit for mechanical and persistent spontaneous itch.

Summary: Findings indicate excitatory interneurons expressing Urocortin 3::Cre (Ucn3+) in the dorsal spinal cord as a valid cellular target for future therapeutic interventions against chronic itch, without affecting normal touch.

Usage: To ablate spinal GRPR+ neurons, mice were given a single intrathecal injection of either Bombesin-SAP or Blank-SAP (400 ng in 10 mL sterile saline). To ablate spinal Npra+ neurons, mice were given a single intrathecal injection of either Nppb-SAP or Blank-SAP (5 mg in 10 mL sterile saline).

Related Products: Bombesin-SAP (Cat. #IT-40), Nppb-SAP (Cat. #IT-69), Blank-SAP (Cat. #IT-21)