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Characterisation of α-1 adrenergic receptors in peripheral blood mononuclear cells of complex regional pain syndrome

Walker, Mollie (2017) Characterisation of α-1 adrenergic receptors in peripheral blood mononuclear cells of complex regional pain syndrome. Honours thesis, Murdoch University.

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Complex regional pain syndrome (CRPS) is a chronic pain condition that may occur after injury or trauma to a limb. The underlying pathophysiology of CRPS is largely undetermined, although CRPS patients commonly present with a persisting inflammatory response in the early stage of the condition and overexpress the α-1 adrenergic receptor (α-1AR) on nociceptors and keratinocytes in the affected limb. In other chronic inflammatory conditions, increased α-1AR mRNA expression in peripheral blood mononuclear cells (PBMCs) has been shown, and is thought to contribute to persisting inflammation. The α-1AR are expressed on a range of cells, including nerve, smooth muscle, skin and immune cells, and bind to adrenaline and noradrenaline released after activation of the sympathetic nervous system. The aims of this project were to examine the mRNA expression of α-1AR subtypes (α-1A, α-1B and α-1D) by qPCR in PBMCs isolated from fractionated blood of CRPS patients, and to quantify the percentages of various PBMC subpopulations compared to healthy controls. Subpopulations of PBMCs were determined by flow cytometry using a panel of fluorescent antibodies that identified CD4+ T cells, CD8+ T cells, CD4+ CD8+ T cells, CD4+ CD25+ T cells, CD8+ CD25+ T cells, B cells, natural killer (NK) cells, NKT cells, and subsets of monocytes. No differences in expression of α- 1AR subtypes in PBMCs of CRPS patients were found when compared to healthy controls. However, a significant increase in the concentration of total PBMCs isolated per mL of blood in CRPS patients and a shift from CD16- to CD16+ monocyte subpopulations was identified when compared to healthy controls. These results show there is an inflammatory component to CRPS and provide preliminary evidence that the persisting inflammation in CRPS patients may originate from over-proliferation of PBMC progenitors in the bone marrow, which is sympathetically modulated by α-1AR, and/or an expansion of other PBMC cell types that were not examined in this project.

Item Type: Thesis (Honours)
Murdoch Affiliation(s): School of Veterinary and Life Sciences
Supervisor(s): Stumbles, Phil and Drummond, Peter
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