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Papers: 14 Oct 2023 - 20 Oct 2023

2023 Oct 15

Brain Behav Immun


Inflammation induces α-adrenoceptor expression in peripheral blood mononuclear cells of patients with complex regional pain syndrome.


Wijaya LK, Stumbles PA, Finch PM, Drummond PD


Persistent regional and systemic inflammation may promote pain and hyperalgesia in complex regional pain syndrome (CRPS). In this study, we investigated whether stimulation of α-adrenoceptors (α-AR) on peripheral blood mononuclear cells (PBMC) might contribute to this inflammatory state. PBMC were isolated from venous blood collected from 21 CRPS patients and 21 sex and age-matched controls. Lipopolysaccharide (LPS), a bacterial toxin, was administered to cultured PBMC for 24 h to trigger inflammation. Exposure to LPS resulted in heightened gene expression of α-AR subtype B (α-AR) in PBMC of CRPS patients relative to controls. Interleukin (IL)-1β and IL-6 levels did not change when the α-AR agonist phenylephrine was administered to naïve PBMC. However, α-AR stimulation following LPS treatment increased IL-6 mRNA and protein levels in PBMC of patients and controls. To investigate the possible consequence of heightened IL-6 levels on immunoglobulin G antibody production, PBMC were stimulated with CD40 ligand and IL-21 to generate plasmablasts (B cells that secrete antibodies). This response was similar in patients and controls. Adding IL-6 to the cell culture medium increased plasmablast differentiation in controls and antibody production both in patients and controls. These findings suggest that the inflammatory cascade associated with elevated levels of IL-6 may generate α-AR expression in CRPS PBMC. A reciprocal interaction between heightened α-AR expression in PBMC and IL-6 secretion may contribute to systemic inflammation and antibody production in CRPS.