Effect of Interactive Neurostimulation Therapy on Inflammatory Response in Patients With Chronic and Recurrent Mechanical Neck Pain.

OBJECTIVE: The purpose of this study is to evaluate the effect of treatment with a novel noninvasive interactive neurostimulation device (InterX5000) on the production of inflammatory biomarkers in chronic and recurrent mechanical neck pain (NP) syndrome. METHODS: This study represents pilot biological data from a randomized controlled clinical trial. Twenty-five NP patients and 14 asymptomatic subjects included for baseline comparison only completed the study. The patients received 6 InterX5000 or placebo treatments within 2 weeks, and pretreatment and post-treatment blood samples were collected for in vitro determination of biomarker production. Whole blood cell cultures were activated by lipopolysaccharide or by the combination of lipopolysaccharide and phytohemagglutinin for 24 to 48 hours. The levels of tumor necrosis factor α (TNFα) and its soluble type II receptor (sTNFR II), interleukin (IL) 1, IL-1 receptor antagonist (IL-1RA), IL-6, IL-10, and monocyte chemotactic protein (CCL2/MCP-1) were determined by specific immunoassays. RESULTS: Compared with asymptomatic subjects, baseline production levels of all proinflammatory mediators (TNFα, IL-1ß, IL-6, and CCL2/MCP-1) were significantly augmented or trended higher (P = .000-.008) in patients with NP. Of the anti-inflammatory markers, only IL-1RA was significantly elevated (P = .004). The increase in IL-10 and tumor necrosis factor receptor II levels did not reach statistical significance. Neither InterX5000 nor placebo therapy had any significant effect on the production of the inflammatory mediators over the study period. CONCLUSION: This investigation determined that inflammatory cytokine pathways are activated in NP patients but found no evidence that a short course of InterX5000 treatment normalized the production of inflammatory biomarkers.

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

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.

Early spondyloarthritis: usefulness of clinical screening.

OBJECTIVES: To evaluate the usefulness of clinical parameters in screening for early SpA in patients meeting Calin's criteria for inflammatory back pain (IBP). METHODS: General practitioners used Calin's criteria for IBP to refer patients younger than 45 years to our early SpA clinic. We obtained the patients' medical history and performed a clinical examination including plain X-rays and magnetic resonance images of all affected areas. Laboratory tests for acute-phase reactants and HLA-B27 were also obtained. Two rheumatologists made a diagnosis of SpA according to the existing criteria. RESULTS: Of the 92 patients referred, 30 (33%) were diagnosed with SpA and 62 (67%) with a non-inflammatory disorder. Spontaneous awakening night pain, the presence of Calin's criteria for IBP and tenderness of the SI joints (SIJs) were independently associated with SpA. Neck pain and reduced cervical spine sagittal movement occurred mostly with non-inflammatory disease. A history of night pain and improvement of pain with exercise but not with rest, as well as expression of HLA-B27 and abnormal CRP levels were significantly more common in patients with SpA. CONCLUSIONS: Specific clinical symptoms such as spontaneous awakening night pain, cervical pain and tenderness of the SIJs on clinical examination appear useful in screening younger patients with back pain for early SpA.

Endocrine and immunologic parameters indicative of 6-month prognosis after the onset of low back pain or neck/shoulder pain.

STUDY DESIGN: Prospective study. OBJECTIVES: To evaluate the prognosis of spine disease by investigating biologic parameters reflecting different physiologic or psychophysiological systems in men and women with acute onset of low back or neck/shoulder complaints. SUMMARY OF BACKGROUND DATA: Psychosocial factors may be of importance to the etiology and prognosis of musculoskeletal disorders. The possible mechanisms, however, remain unclear. Stress-induced long-lasting energy mobilization resulting in inhibited anabolism has been discussed. Using a theoretical framework within stress physiology, such psychophysiological processes were recorded by measures of substances representing the anabolic, catabolic, immunologic, and opioid systems. METHODS: The study comprised 67 working men and women 21 to 59 years of age seeking care by any caregiver for acute low back and/or neck/shoulder pain. Blood samples were taken and analyzed for 3 methyl 5hydroxy phenylethylene glycol (MHPG, reflecting sympathoadrenomedullary activity), DHEA-s (anabolism), immunoglobulin E, interleukin 6 (immune activity), and beta-endorphin (pain regulation). The participants were followed up for 6 months after the blood samples had been drawn. RESULTS: In women, low MHPG, low DHEA-s, and low beta-endorphin predicted persistent disability due to low back complaints. Few significant findings were made for self-reported pain, for neck/shoulder complaints, and for men. CONCLUSION: Disturbances of the regulation of certain biologic parameters might be indicators of a prolonged course of low back disease in women. Prospective studies are necessary to enable causal conclusions.