Elevated blood levels of inflammatory monocytes (CD14+CD16+) in patients with complex regional pain syndrome

Abstract

SummaryComplex regional pain syndrome (CRPS) is a chronic pain disorder. Although its pathophysiology is not completely understood, neurogenic inflammation is thought to play a significant role. Microglia and astrocytes are activated following tissue injury or inflammation and have been reported to be both necessary and sufficient for enhanced nociception. Blood-borne monocytes/ macrophages can infiltrate the central nervous system (CNS) and differentiate into microglia resulting in hypersensitivity and chronic pain. The primary aim of this study was to evaluate the proportion of the proinflammatory CD14 + CD16 + monocytes as well as plasma cytokine levels in blood from CRPS patients compared to age-and gender-matched healthy control individuals. + CD16 + monocytes became elevated prior to or after developing CRPS. In either case, the elevation of blood proinflammatoty monocytes prior to the initiating event may predispose individuals for developing the syndrome whereas the elevation of blood proinflammatory monocytes following the development of CRPS may be relevant for its maintenance. Further evaluation of the role the immune system plays in the pathogenesis of CRPS may aid in elucidating disease mechanisms as well as the development of novel therapies for its treatment.

Lenalidomide for Complex Regional Pain Syndrome Type 1: Lack of Efficacy in a Phase II Randomized Study

“…This subgroup might be a better target for trials of immunomodulatory agents. In addition to altered plasma cytokine levels, other significant changes reported in people with CRPS include altered levels of plasma amino acids, 41 serum and saliva antioxidative parameters, 11 blood levels of inflammatory monocytes, 31 and altered intestinal microbial communities. 29 These markers might help define subgroups amenable to specific treatments.…”

9-cis Retinoic Acid Inhibits Inflammatory Responses of Adherent Monocytes and Increases Their Ability to Induce Classical Monocyte Migration

“…We show that the adherent monocytes in our study are strongly enriched in the CD14dimCD16+ monocyte subset. This subset, which represents only about 10% of the total monocyte population in healthy human blood, is shown to be strongly increased in acute inflammatory conditions like sepsis, autoimmune diseases like rheumatoid arthritis and diabetes and in conditions accompanied by chronic pain [20][21][22] . It has also been proposed that CD14dimCD16+ monocytes develop from classical CD14high monocytes [23] and exhibit a greater ability to adhere to endothelium [24] .…”

Inflammation in complex regional pain syndrome

“…14,19,20,22,23 Only 2 studies compared the levels of inflammatory factors in the affected and the unaffected limbs. These found that the levels of IL-6, 2 IL-1b, 2 TNFa, 2 NPY, 2 PGE2, 2 and CGRP 2,17 were not significantly different between the affected and the unaffected limb.…”

“…23 Healthy controls were utilized by most studies, [14][15][16][17][19][20][21][22] with the exception of 2 that used subjects with fractures or osteoarthritis, 18 and the unaffected arm 2 as controls. The results are presented in figures 2 and 3.…”

“…Inflammatory factor concentrations in blood were reported in 4 acute CRPS studies, [15][16][17][18] 9 chronic CRPS studies, 2,14,16-22 and 1 mixedduration study. 23 Healthy controls were utilized by most studies, [14][15][16][17][19][20][21][22] with the exception of 2 that used subjects with fractures or osteoarthritis, 18 and the unaffected arm 2 as controls. The results are presented in figures 2 and 3.…”