The association between pro-inflammatory biomarkers and nonspecific low back pain: a systematic review

BACKGROUND CONTEXT: About 85% of the patients with low back pain seeking medical care have nonspecific low back pain (NsLBP), implying that no definitive cause can be identified. Nonspecific low back pain is defined as low back pain and disability which cannot be linked to an underlying pathology, such as cancer, spinal osteomyelitis, fracture, spinal stenosis, cauda equine, ankylosing spondylitis, and visceral-referred pain. Many pain conditions are linked with elevated serum levels of pro-inflammatory biomarkers. Outcomes of interest are NsLBP and the level of pro-inflammatory biomarkers. PURPOSE: To unravel the etiology and get better insight in the prognosis of NsLBP, the aim of this study was to assess the association between pro-inflammatory biomarkers and the presence and severity of NsLBP. STUDY DESIGN: A systematic literature search was made in Embase, Medline, Cinahl, Webof-science, and Google scholar up to January 19th 2017. METHODS: Included were cross-sectional and cohort studies reporting on patients aged over 18 years with NsLBP, in which one or more pro-inflammatory biomarkers were measured in blood plasma. The methodological quality of the included studies was assessed using the Newcastle Ottawa Scale. A best-evidence synthesis was used to summarize the results from the individual studies, meaning that the included studies were ranked according to the consistency of the findings and according to their methodological quality score using the Newcastle Ottawa Scale. RESULTS: Included were 10 studies which assessed four different pro-inflammatory biomarkers. For the association between the presence of NsLBP and C-reactive protein (CRP), interleukin 6 (IL-6) and tumor necrosis factor (TNF)-alpha limited, conflicting and moderate evidence, respectively, was found. For the association between the severity of NsLBP and CRP and IL-6, moderate evidence was found. For the association between the severity of NsLBP and TNF-alpha and RANTES Regulated on Activation, Normal T Cell Expressed and Secreted conflicting and limited evidence, respectively, was found. CONCLUSIONS: This study found moderate evidence for (i) a positive association between the pro-inflammatory biomarkers CRP and IL-6 and the severity of NsLBP, and (ii) a positive association between TNF-alpha and the presence of NsLBP. Conflicting and limited evidence was found for the association between TNF-alpha and Regulated on Activation, Normal T Cell Expressed and Secreted and severity of NsLBP, respectively. (C) 2018 Elsevier Inc. All rights reserved.