Elevated production of inflammatory mediators including nociceptive chemokines in patients with neck pain: A cross-sectional evaluation

Abstract

Objective: This study investigated whether the production of inflammatory mediators and chemotactic cytokines (chemokines) is altered in patients with chronic and recurrent neck pain (NP). Methods: Cross-sectional data evaluating blood and serum samples were obtained from 27 NP patients and 13 asymptomatic (control) subjects recruited from a chiropractic outpatient clinic. Cell cultures were activated by lipopolysaccharide (LPS) and phytoheamagglutinin for 24 to 48 hours. The levels of tumor necrosis factor α (TNF-α), monocyte chemotactic protein 1, also known as CCL2 (CCL2/MCP-1), and macrophage inflammatory protein 1α or CCL3 (CCL3/MIP-1α) were determined by specific immunoassays. Serum levels of nitric oxide metabolites were evaluated simultaneously, in vanadium III-reduced samples, by Griess reaction. Results: Low levels of constitutive (spontaneous) TNF-α production were present in 7 of the 27 cultures from patients with NP. Both LPS-induced TNF-α production and inducer (LPS/phytoheamagglutin)-stimulated production of CCL2 were significantly elevated (P =.00) in patients compared with controls. In patients, the constitutive synthesis of CCL3 occurred significantly more frequently (P =.00) and ranged from 30 to more than 2000 pg/mL. Finally, serum levels of nitric oxide were significantly elevated (P =.00) in NP patients. Conclusions: Production of inflammatory mediators was consistently elevated in NP patients in this study, both in vitro and in vivo, and activation of inflammatory pathways was accompanied by up-regulation of CC chemokine synthesis. This suggests that, in NP patients, CC chemokines may be involved in regulation of local inflammatory response through recruitment of immune cells to the inflamed tissue and exert pronociceptive effects. © 2011 National University of Health Sciences.