Central mechanisms may play a role in pain perception during osteoarthritis (OA).Local inflammation (which involves production of pro-inflammatory cytokines such as interleukin (IL) 4 TNF-alpha, IL-6 and IL-8) is considered to be a major source of pain.

Certain therapies that specifically interfere with the expression or actions of pro-inflammatory cytokines have been explored. NSAIDs have analgesic, antipyretic and anti-inflammatory properties and are extensively prescribed for several musculoskeletal disorders. Indeed, the Osteoarthritis Research Society International (OARSI) recently recommended the use of NSAIDs for management of knee and hip OA in symptomatic patients. These drugs have been shown to influence cytokine metabolism in the synovial fluid of OA patients with satisfactory relief of painful osteoarthritic joints.

The aim of the current study was to explore whether NSAID treatment inhibits TNF-alpha, IL-6, IL-8, and VEGF secretion in the synovial fluid of osteoarthritic joints. In particular, diclofenac, ibuprofen and celecoxib were studied. Under the hypothesis that relationships between proinflammatory cytokines and the clinical status of OA patients are possible, we also evaluated the association between the concentration of these molecules in the osteoarthritic knee synovial fluid and the pain and functional status of patients with OA. The effects of NSAIDS on signal transduction pathways in the synovial membrane were also investigated.

not desired

Inclusion Criteria:

Patients eligible for the study were:

• older than 50 years and
• had primary knee OA diagnosed according to the clinical and radiological criteria of the American Rheumatism Association.

Further inclusion criteria were:

• clinical signs of joint inflammation (warmth, swelling or effusion) and
• a disease severity grade 2 or 3 according to the Kellgren-Lawrence classification

Exclusion Criteria:

• allergy to NSAIDs,
• progressive serious medical conditions (such as cancer, AIDS or end-stage renal disease),
• history of gastrointestinal ulcer or bleeding,
• a hemoglobin concentration lower than 11.5 g/dL,
• renal diseases (serum creatinine concentration more than 1.2 times the upper limit of the normal range according to the central laboratory definition reference values), or
• liver dysfunction (serum alanine or aspartate transaminase concentrations more than 1.5 times the upper limit of normal range according to the central laboratory definition reference values).