Abstract
BackgroundInflammatory 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.MethodsLevels 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.ResultsPain 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.ConclusionsIL-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.
Highlights
Inflammatory mediators in the synovial fluid (SF) play critical roles in the initiation and development of pain in knee osteoarthritis (KOA)
range of motion (ROM) became more limited (Fig. 1a), and the WOMAC score increased (Fig. 1b); worsening K-L grade led to limited ROM (r = − 0.499, p < 0.001) and an increased WOMAC score (r = 0.493, p < 0.001) (Fig. 2a and Fig. 2b), which indicated that knee function was gradually lost
We found that interleukin 1β (IL-1β) (p = 0.002) and interleukin 6 (IL-6) (p = 0.023) expression differed significantly among the four K-L groups (Fig. 3a and Fig. 3b)
Summary
Inflammatory mediators in the synovial fluid (SF) play critical roles in the initiation and development of pain in knee osteoarthritis (KOA). In the past decade, inflammation has been found to play a critical role in the pathogenesis of KOA and to contribute to the initiation and development of pain [1, 5, 6]. Numerous types of SF inflammatory mediators, including inflammatory cytokines, matrix catabolic proteases and neuropeptides, have important functions. Expression of these cytokines in osteoarthritis pain remains unresolved, and different studies have arrived at conflicting conclusions regarding interleukin 1β (IL-1β), interleukin 6 (IL-6) and tumor necrosis factor (TNF-α) [7,8,9]. It is necessary to further explore the roles of these inflammatory mediators in pain and identify candidate inflammatory mediators associated with pain
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