Osteoarthritis: the genesis of pain

Fu, Kai; Robbins, Sarah R; McDougall, Jason J.

doi:10.1093/rheumatology/kex419

Cited by 232 publications

(198 citation statements)

References 103 publications

Supporting

Mentioning

194

Contrasting

Unclassified

Order By: Relevance

“…Pain is the most prominent symptom of knee osteoarthritis (KOA) and the major driver of clinical decision-making. Despite great progress in the understanding of the molecular and cellular 3 mechanisms of KOA, the treatment of pain is still a challenge in the clinic (1)(2)(3)(4). Therefore, etiological investigation of pain is not only helpful for understanding KOA but also critical for developing new medications to relieve it.…”

Section: Introductionmentioning

confidence: 99%

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

Liu

et al. 2019

Preprint

View full text Add to dashboard Cite

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.

show abstract

Section: Introductionmentioning

confidence: 99%

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

Liu

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…While bone remodeling, loss of cartilage, and narrowing of the joint space are the characteristic morphological changes observed in OA, pain often is associated with the presence of inflammation (synovitis) [4,6,84]. In such cases, peripheral nerves in the various degenerating joint tissues become exposed to the intraarticular environment rich in cytokines, chemokines, proteases, prostaglandins, and neuropeptides, which serve as ligands for nociceptors [86,[90][91][92]. Ligand binding lowers the threshold of these receptors and sensitizes the peripheral neurons, such that even normal joint movement triggers a pain response [86,87,93].…”

Section: Identifying the Mec Based On Prostaglandin E2 (Pge2) Inhibitmentioning

confidence: 99%

“…In addition to nociceptive pain, neuropathic pain may result from direct damage to the nerves in the injured joint, dorsal root ganglia, and spinal cord [11,96,97]. Neuropathic pain is not responsive to NSAIDs [92].…”

Section: Identifying the Mec Based On Prostaglandin E2 (Pge2) Inhibitmentioning

confidence: 99%

“…Central sensitization can be another major component of OA pain, manifesting as increased sensitivity to noxious stimuli (hyperalgesia) or interpretation of non-noxious stimuli as painful (allodynia) [27,92]. Although there is some evidence that diclofenac crosses the blood-brain barrier [98,99], low concentrations are likely to enter the central nervous system following topical administration given the limited systemic exposure associated with topical use.…”

Section: Identifying the Mec Based On Prostaglandin E2 (Pge2) Inhibitmentioning

confidence: 99%

“…Thus, OA pain may have peripheral elements (e.g., inflammation, sensitization of peripheral neurons, direct damage to nerves) as well as central components (e.g., hyperalgesia and allodynia), and these heterogeneous underlying mechanisms may respond differently to treatment [5,92,100]. Patients with earlier-stage OA pain related to active inflammation, particularly inflammatory mediators downstream of PGE2, would likely have the best response to topical NSAIDs based on their mechanism of action, but this remains to be confirmed.…”

Section: Identifying the Mec Based On Prostaglandin E2 (Pge2) Inhibitmentioning

confidence: 99%

See 2 more Smart Citations

Topical Diclofenac, an Efficacious Treatment for Osteoarthritis: A Narrative Review

Revel¹,

Fayet²,

Hagen³

2020

Rheumatol Ther

View full text Add to dashboard Cite

Multiple head-to-head trials have demonstrated that topical nonsteroidal anti-inflammatory drugs (NSAIDs), including topical diclofenac, provide at least equivalent analgesia, improvement in physical function, and reduction of stiffness compared with oral NSAIDs in osteoarthritis and have fewer systemic adverse events. While efficacy of topical diclofenac in osteoarthritis is well established, understanding of the time to onset of action, duration of effect, and the minimum effective concentration is limited. Factors likely to influence these parameters include drug penetration and localization. Diclofenac concentrations in the joint tissues are likely to be more relevant than plasma concentrations. However, although

show abstract

Association Between Structural Change Over Eighteen Months and Subsequent Symptom Change in Middle‐Aged Patients Treated for Meniscal Tear

Katz

Collins

Jones

et al. 2022

Arthritis Care & Research

View full text Add to dashboard Cite

Objective. Middle-aged subjects with meniscal tear treated with arthroscopic partial meniscectomy (APM) experience greater progression of damage to joint structures on imaging than subjects treated nonoperatively. It is unclear whether these changes are clinically relevant. The goal of this study was to assess whether worsening in magnetic resonance imaging (MRI)-assessed tissue damage over 18 months leads to subsequent worsening in knee pain over the subsequent 3.5 years.Methods. We used data from the Meniscal Tear in Osteoarthritis Research (MeTeOR) trial of APM versus physical therapy for subjects ages ≥45 years with knee pain, cartilage damage, and meniscal tear. We assessed whether change in cartilage surface area damage score (and other structural measures) from baseline to 18 months, assessed on MRI with the MRI Osteoarthritis Knee Score (MOAKS) system, was associated with change in Knee Injury and Osteoarthritis Outcome Score (KOOS) pain score (range 0-100; 100 = worst) from 18 to 60 months.Results. The primary analysis included 168 subjects with complete MRI data at baseline and 18 months and KOOS data at 18 and 60 months. We did not observe clinically important associations between change in cartilage surface area score between baseline and 18 months and change in pain scores from 18 to 60 months. Pain scores in the worst tertile for cartilage surface area damage score progression worsened by 0.45 points more than in the best tertile (95% confidence interval -4. 45, 5.35). Similarly, we did not observe clinically important associations between changes in bone marrow lesions, osteophytes, or synovitis and subsequent pain.Conclusion. We did not observe clinically important associations between early changes in cartilage damage and other structural measures and worsening in pain over the subsequent 3.5 years. Further follow-up is required to assess this association over a longer follow-up period.ClinicalTrials.gov identifier: NCT00597012.

show abstract

Osteoarthritis: the genesis of pain

Cited by 232 publications

References 103 publications

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

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

Topical Diclofenac, an Efficacious Treatment for Osteoarthritis: A Narrative Review

Association Between Structural Change Over Eighteen Months and Subsequent Symptom Change in Middle‐Aged Patients Treated for Meniscal Tear

Contact Info

Product

Resources

About