Gastrin-Releasing Peptide/Gastrin-Releasing Peptide Receptor Participation in Itch Sensation Signaling in the Spinal Cord of Uremic Pruritus Mice

Altern Ther Health Med. 2024 Apr 18:AT10256. Online ahead of print.

Abstract

Background: Uremic pruritus is a prevalent clinical symptom in maintenance dialysis patients. Existing evidence establishes a connection between itch transmission and the gastrin-releasing peptide/gastrin-releasing peptide receptor signaling pathway.

Objective: To investigate the involvement of the gastrin-releasing peptide/gastrin-releasing peptide receptor in itch sensation signaling within the spinal cord of uremic pruritus.

Design: An animal study was conducted.

Setting: The research was conducted at the First Hospital of Hebei Medical University.

Participants: A total of 50 male C57BL/6J mice (weight: 30-40 g) were acquired from Beijing Weitonglihua Laboratory Animal Center.

Interventions: Mice were categorized into five groups: normal, sham, Y, A, and B. The Y group received intrathecal injections of saline (5 ul). The A group received intrathecal injections of gastrin-releasing peptide (0.1 nmol, 5 ul), and the B group received intrathecal injections of the gastrin-releasing peptide receptor antagonist RC-3095 (0.3 mmol, 5 ul).

Primary outcome measures: (1) Pruritus behavior of mice and (2) expression of gastrin-releasing peptide, gastrin-releasing peptide receptor, and inositol trisphosphate.

Results: Scratching times in the Y group significantly surpassed those of normal and sham groups, increasing over time. Gastrin-releasing peptide and receptor expression rose in the uremic pruritus mouse model compared to normal and sham groups (P < .05). Expression of gastrin-releasing peptide and its receptor was significantly elevated in the uremic pruritus mouse model compared to the normal and sham groups (P < .05). Inositol trisphosphate expression in the dorsal spinal horn of Y group mice increased compared to normal and sham groups. Intrathecal gastrin-releasing peptide heightened inositol trisphosphate expression, while the peptide receptor antagonist RC-3095 reduced it. Y group scratching times were higher than normal and sham groups, increasing after intrathecal gastrin-releasing peptide but decreasing after RC-3095 injection.

Conclusion: The gastrin-releasing peptide/gastrin-releasing peptide receptor signaling pathway is involved in the development of uremic pruritus.