| 论文简介 |
Intrathecal morphine infusion is often applied to treat chronic pain related to cancer and other conditions. However, persistent pain can be caused by nerve compression due to granuloma formation. In this study, a mouse model of morphine induced granuloma formation by intrathecal catheterization morphine infusion into the atlanto-occipital membrane of the foramen magnum was established in wild-type (WT) mice, MrgprB2-mutant (MrgprB2-/-) mice, and in mast cell-deficient W-sash c-kit mutant KitW-sh/W-sh (Kit) mice. Heat-related pain after surgery was performed to investigate the anti-pain effect of morphine. Hematoxylin and eosin staining and immuno-fluorescence staining of the spinal cord were applied to analyze the mechanism of granuloma formation. Morphine-induced mast cell degranulation was assessed by measuring the Ca2+ influx and mediator release. Anaphylactoid reactions were measured after subcutaneous morphine infusion to the paws. Chemokine release by mast cells was determined by Human XL Cytokine Array. Experiments with WT, MrgprB2-/- and Kit mice demonstrated that morphine activated mast cells and inflammatory cell aggregation through MrgprB2 in intrathecal infusion sites. The chemokine production of human mast cells demonstrated that granuloma formation is correlated with chemokines release. In addition, morphine activated mouse primary mast cells and de novo chemokine synthesis via the MRGPRX2 in human LAD2 cells. We concluded that granuloma formation during intrathecal morphine infusion was associated with MrgprB2/X2. Reducing MRGPRX2 potentially blocks morphine-induced side effects, including granuloma formation. |
(创新港)
