Association Between the Plasma Levels of Mediators of Inflammation With Pain and Disability in the Elderly With Acute Low Back Pain

Jacobsen

Annals of the New York Academy of Sciences

et al. 2017

272

221

Biomarkers are biological characteristics that can be used to indicate health or disease. This paper reviews studies on biomarkers of low back pain (LBP) in human subjects. LBP is the leading cause of disability, caused by various spine-related disorders, including intervertebral disc degeneration, disc herniation, spinal stenosis, and facet arthritis. The focus of these studies is inflammatory mediators, because inflammation contributes to the pathogenesis of disc degeneration and associated pain mechanisms. Increasingly, studies suggest that the presence of inflammatory mediators can be measured systemically in the blood. These biomarkers may serve as novel tools for directing patient care. Currently, patient response to treatment is unpredictable with a significant rate of recurrence, and, while surgical treatments may provide anatomical correction and pain relief, they are invasive and costly. The review covers studies performed on populations with specific diagnoses and undefined origins of LBP. Since the natural history of LBP is progressive, the temporal nature of studies is categorized by duration of symptomology/disease. Related studies on changes in biomarkers with treatment are also reviewed. Ultimately, diagnostic biomarkers of LBP and spinal degeneration have the potential to shepherd an era of individualized spine medicine for personalized therapeutics in the treatment of LBP.

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Studies Of Lbp In Patients With Undefined Diagnoses (Table 1)mentioning

confidence: 99%

See 1 more Smart Citation

Inflammatory biomarkers of low back pain and disc degeneration: a review

Jacobsen

Annals of the New York Academy of Sciences

et al. 2017

272

221

“…Serum biomarkers are quantitative and objective measurements, and can be used as indicators of biological processes involved in discogenic pain or as indicators for systematic disorders such as osteoporosis . Currently reported candidates for serum biomarkers for back pain include C‐C motif ligand 5, C‐X‐C motif ligand 6, IL‐6, high‐sensitivity C‐reactive protein, TNF‐α, IL‐1β, and type 2 collagen . Matrix‐assisted laser desorption ionization time‐of‐flight mass spectrometry (MALDI‐TOF‐MS) has also been shown to distinguish discogenic LBP from the other forms of chronic back pain, and complement C3 and fibrinogen are potential serum biomarkers for discogenic back pain .…”

Section: Noninvasive Diagnostic Tools For Discogenic Painmentioning

confidence: 99%

“…(52) Currently reported candidates for serum biomarkers for back pain include C-C motif ligand 5, C-X-C motif ligand 6, IL-6, high-sensitivity C-reactive protein, TNF-a, IL-1b, and type 2 collagen. (52)(53)(54)(55)(56)(57)(58)(59) Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) has also been shown to distinguish discogenic LBP from the other forms of chronic back pain, and complement C3 and fibrinogen are potential serum biomarkers for discogenic back pain. (60) Nevertheless, serum cytokines and other biomarkers can be from a variety of sources of systemic conditions, so their specificity to discogenic back pain conditions must be validated with other methods.…”

Section: Noninvasive Diagnostic Tools For Discogenic Painmentioning

confidence: 99%

Discogenic Back Pain: Literature Review of Definition, Diagnosis, and Treatment

et al. 2019

Discogenic back pain is multifactorial; hence, physicians often struggle to identify the underlying source of the pain. As a result, discogenic back pain is often hard to treat—even more so when clinical treatment strategies are of questionable efficacy. Based on a broad literature review, our aim was to define discogenic back pain into a series of more specific and interacting pathologies, and to highlight the need to develop novel approaches and treatment strategies for this challenging and unmet clinical need. Discogenic pain involves degenerative changes of the intervertebral disc, including structural defects that result in biomechanical instability and inflammation. These degenerative changes in intervertebral discs closely intersect with the peripheral and central nervous systems to cause nerve sensitization and ingrowth; eventually central sensitization results in a chronic pain condition. Existing imaging modalities are nonspecific to pain symptoms, whereas discography methods that are more specific have known comorbidities based on intervertebral disc puncture and injection. As a result, alternative noninvasive and specific diagnostic methods are needed to better diagnose and identify specific conditions and sources of pain that can be more directly treated. Currently, there are many treatments/interventions for discogenic back pain. Nevertheless, many surgical approaches for discogenic pain have limited efficacy, thus accentuating the need for the development of novel treatments. Regenerative therapies, such as biologics, cell‐based therapy, intervertebral disc repair, and gene‐based therapy, offer the most promise and have many advantages over current therapies. © 2019 The Authors. JBMR Plus Published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research

Journal Orthopaedic Research

Role of CD14‐positive cells in inflammatory cytokine and pain‐related molecule expression in human degenerated intervertebral discs

Miyagi

Uchida

Takano

et al. 2020

Multiple human and animal studies suggest that the upregulation of inflammatory cytokines and other pain‐related molecules in degenerated or injured intervertebral discs (IVDs) may cause discogenic low back pain (LBP). We previously reported that macrophages in injured IVD in mice produced inflammatory cytokines, but not other pain‐related molecules. CD14 is a monocyte marker expressed mainly by macrophages. The aim of the current study was to evaluate the role of CD14‐positive cells in inflammatory cytokine and pain‐related molecule expression in human degenerated IVD. IVD samples were harvested from 14 patients, including 10 with lumbar spinal stenosis, four with adult spinal deformity, and one with lumbar disc herniation during spinal interbody fusion surgery. Harvested IVD‐derived mononuclear cells were obtained and CD14‐positive (+) and CD14‐negative (−) cells were separated using CD14 antibody and streptavidin‐labeled magnetic beads. Inflammatory cytokines messenger RNA (mRNA) in the CD14(+) and CD14(−) cells, including tumor necrosis factor ɑ (TNFA), in, terleukin‐1β (IL1B) and IL6, were determined using quantitative polymerase chain reaction (qPCR) and their expression levels were compared. To evaluate factors controlling the regulation of pain‐related molecules mRNA expression, cultured CD14(−) and CD14(+) cells from IVDs were stimulated with recombinant human TNF‐ɑ and IL‐1β and levels of pain‐related molecules, including calcitonin gene‐related peptide (CGRP) and nerve growth factor (NGF) were determined using qPCR. Levels of TNFA, IL1B, IL6, and NGF in CD14(+) cells were significantly increased compared with those in CD14(−) cells (TNFA, p = 0.006; IL1B, p = .017; IL6, p = .010; NGF, p = .027). Following TNFA stimulation, NGF levels were significantly increased in CD14(−) and CD14(+) cells (CD14(−), p = .003; CD14(+), p < .001) and CGRP was significantly increased in CD14(−) IVD cells (p = .040). Following IL1B stimulation, NGF levels were significantly increased in CD14(−) cells (p = .004). CD14(+) cells had higher TNFA, IL1B, IL6, and NGF expressions than CD14(−) cells in human degenerated IVDs. Additionally, TNFA stimulation promoted the upregulation of NGF and CGRP in CD14(−) cells. These findings suggested that CD14(+) cells directly and indirectly contributed to inflammatory cytokine and pain‐related molecule expression in human degenerated IVD. CD14(+) cells might be important in the pathological mechanism of chronic discogenic LBP in humans.