Profiling of inflammatory mediators in the synovial fluid related to pain in knee osteoarthritis

Abstract

Background: Inflammatory mediators in the synovial fluid (SF) play critical roles in the initiation and development of pain in knee osteoarthritis (KOA). However, data for inflammatory marker expression are conflicting, and the role of SF inflammatory mediators in neuropathic pain is not clear. Therefore, the aim of this study was to identify SF inflammatory mediators associated with nociceptive and neuropathic pain in KOA. Methods: Levels of IL-1β, IL-6, TNF-α, macrophage colony-stimulating factor, MMP-3, MMP-13, metalloproteinase with thrombospondin motifs 5, calcitonin gene-related peptide, neuropeptide Y, substance P and bradykinin were measured using enzyme-linked immunosorbent assays in 86 patients. Nociceptive pain was assessed using the numeric rating scale (NRS), visual analog scale (VAS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score. Neuropathic pain was determined using the PainDETECT questionnaire. Moreover, knee function was evaluated by the WOMAC score and range of motion (ROM) assessments. Radiological grade was defined using the Kellgren-Lawrence (K-L) grading scale. Results: Pain scores measured using different methods correlated highly with each other. A worse K-L grade and knee function were associated with worse pain. Expression of IL-1β and IL-6 was increased in the early stage compared with the late stage. The NRS score correlated positively with age, K-L grade, and the WOMAC score and negatively with ROM and TNF-α expression. The VAS correlated positively with age, K-L grade, and the WOMAC score but negatively with ROM and levels of IL-1β, IL-6 and TNF-α. The WOMAC pain score did not correlate with any of the inflammatory mediators measured; it correlated only with ROM. The PainDETECT score correlated only with the WOMAC score. Expression of other inflammatory mediators did not correlate with any of the pain scores. Conclusions: IL-1β, IL-6 and TNF-α play critical roles in pain in the early stage of KOA and correlate with pain. The catabolic enzymes and neuropeptides measured do not correlate with nociceptive and neuropathic pain. New biomarkers related to pain in the late stage need to be further investigated.

<p>Intra-Articular Injection of Amniotic Membrane and Umbilical Cord Particulate for the Management of Moderate to Severe Knee Osteoarthritis</p>

“… 54 Collectively, these actions may help to resolve inflammation and attenuate cartilage degradation, both of which play an important role in the pathology and clinical manifestations of OA. 2 , 3 …”

“…2 This inflammation, coupled with progressive articular erosion, causes pain, progressive loss of function, and diminished quality of life. 3,4 Given its high prevalence, knee OA is a leading cause of physical disability in the aging population. 5 There are currently few effective conservative treatment modalities for symptomatic knee OA, none of which prevent disease progression.…”

Randomized, Placebo‐Controlled Analysis of the Knee Synovial Environment Following Platelet‐Rich Plasma Treatment for Knee Osteoarthritis

“…Correlation tests have been previously used to assess WOMAC data. 36,37 We used nonparametric correlation tests and determined that lower scores at 3, 6, and 12 months correlated with saline or PRP treatment for pain, stiffness, physical function, and VAS (Table S2). Incidence of significant correlations appeared to be more frequent at 6 months following treatment for both saline and PRP when compared to baseline.…”

Efficacy of Methotrexate on Rat Knee Osteoarthritis Induced by Monosodium Iodoacetate

“… 7 Therefore, the boundary between inflammatory OA and degenerative OA is becoming unclear as understanding of the ongoing immune processes within a degenerate joint becomes clearer. 8 , 9 In particular, inflammation has been strongly implicated in the pathogenesis of OA. 10 , 11 Previous studies have reported increased levels of pro-inflammatory cytokines, such as tumor necrosis factor (TNF) α, interleukin (IL)-1β, and IL-6 in OA fluid and tissue.…”