(303) - The mast cell receptor mrgprb2 contributes to inflammatory pain via immune cell modulation

Abstract

Although the mechanisms of postoperative pain are still incompletely understood, research has shed light on one potentially important immune cell. As one of the key effector cells in the inflammatory process, mast cells are an important contributor to pain pathophysiology. The role of mast cells in mediating postoperative pain is incompletely understood, although studies using mast cell stabilizers demonstrate that this immune cell is involved in contributing to nociception in animal models of postoperative pain. Thus, there is a compelling need for fundamental research aimed at understanding the mechanisms of mast cells in postoperative pain. Towards this objective, our lab has previously published data identifying a novel mast cell specific receptor, Mas-related G-protein-coupled receptor B2 (MRGB2) and its human orthologue, MRGX2, in non-allergenic activation of mast cells. To evaluate the role of MRGB2 in postoperative pain we utilized a hindpaw incision model. After baselines were measured, mice were anesthetized and a 5-mm incision beginning 2 mm from the proximal edge of the right heel was made. Curved forceps elevated the underlying muscle. A mattress suture of 8–0 nylon on a TG175-8 needle were then used to close the incision. Antibiotic ointment (Bacitracin Zinc Ointment) was then applied. Male C57bl/6 wild-type (WT) or MRGB2KO (n = 6/group) were tested 24 h after incision surgery. Behavioral testing was done utilizing the radiant heat test and Von Frey filaments. At 24 hours post-surgery we saw significant reduction in both mechanical and thermal allodynia in MRGB2 KO mice but not WT, indicating that mast cells contribute to postoperative allodynia via MRGB2. Further study of the mechanisms underlying the role of this receptor in mediating incision induced pain may provide potential strategies for the development of novel analgesics to treat debilitating postoperative pain.