Ultrasound detected synovial change and pain response following intra-articular injection of corticosteroid and a placebo in symptomatic osteoarthritic knees: a pilot study

Intra-articular injection (IAI) of steroid is a safe and effective treatment for painful knee osteoarthritis (OA).1 The mechanism of action is thought to be partly mediated by an anti-inflammatory effect on the synovium which may be detected by changes observed on ultrasound (US) examination.2 Placebo IAI of saline can also significantly reduce pain though the mechanisms are not generally thought to associate with a peripheral effect.3–5 This pilot study aimed to investigate whether improved knee pain correlated with improved US measures following IAI of a corticosteroid or a placebo in OA knees.

Twenty-five participants with painful knee OA (Kellgren and Lawrence grade ≥2) were randomised to one of two treatment sequences (IAI of methylprednisolone (40 mg in 1 mL) followed by IAI of saline placebo (1 mL, 0.9%), or vice versa) to their most painful knee. Synovial fluid equal to volume injected …

Intra-articular injection (IAI) of steroid is a safe and effective treatment for painful knee osteoarthritis (OA). 1 The mechanism of action is thought to be partly mediated by an antiinflammatory effect on the synovium which may be detected by changes observed on ultrasound (US) examination. 2 Placebo IAI of saline can also significantly reduce pain though the mechanisms are not generally thought to associate with a peripheral effect. [3][4][5] This pilot study aimed to investigate whether improved knee pain correlated with improved US measures following IAI of a corticosteroid or a placebo in OA knees.
Twenty-five participants with painful knee OA (Kellgren and Lawrence grade ≥2) were randomised to one of two treatment sequences (IAI of methylprednisolone (40 mg in 1 mL) followed by IAI of saline placebo (1 mL, 0.9%), or vice versa) to their most painful knee. Synovial fluid equal to volume injected (1 mL) was aspirated from the knee joint. No participant had inflammatory arthritis or had IAI of steroid within the previous 3 months. The second injection was delivered after knee pain returned to its preinjection level. Pain was assessed using a 100 mm visual analogue scale (VAS) and Western Ontario and McMaster Osteoarthritis Knee Index (WOMAC). 6 US examination was carried out by a blinded assessor immediately prior to and 1 week following each injection, using a Toshiba Aplio SSA-770A machine with a multifrequency (7-12 MHz) linear array transducer. A standardised protocol reflecting European League Against Rheumatism (EULAR) and Outcome Measures in Rheumatology (OMERACT) definitions was used. 7 8 Maximal depth of effusion, synovial hypertrophy and popliteal cysts were measured in millimetres (mm).
Ten men and 15 women (mean age, 72 years (SD 7.8)) were enrolled and completed the study. All baseline characteristics were balanced for both sequence groups ( p<0.05). Independent t tests showed no order effect for pain response following the steroid injection ( p=0.87) or placebo injection ( p=0.72) and there was no significant difference in the mean time (days) between injections (steroid first=95 (SD 65); placebo first=81 (SD 47); p=0.81).
As expected, significant improvements in pain VAS were observed following both injections (mean difference: steroid −17.4 mm SD (26.8), p=0.003; placebo −13.4 mm SD (22.4), p=0.006) (table 1, figure 1A). Maximal depth of synovial hypertrophy was significantly reduced following the steroid injection (mean difference −0.9 mm SD (2.2), p=0.04) and was non-significantly reduced following the placebo injection (mean difference −1.0 mm SD (3.7) p=0.91) (table 1, figure 1B). No change in effusions (table 1, figure 1C) or popliteal cysts were observed following either injection (table 1). We found no correlation between change in pain VAS and change in US measures following either injection though this may be related to the small sample size.
The observed improvement in synovial hypertrophy following IAI of steroid accords with a recent MRI study which reported a significant reduction in mean synovial volume following IAI of steroid. 9 However, we also observed a reduction in synovial hypertrophy following the placebo injection which mirrored the changes following the steroid. The analgesic effects of a placebo are considered to occur through expectancy-induced descending inhibitory mechanisms such as release of endogenous opioid but it has also been suggested that a reduction of local inflammation may arise through activation of the hypothalamic-pituitary-adrenal axis as part of expectancy-induced descending inhibition of pain. 10 We believe that this may be the first study to show a possible peripheral ('anti-inflammatory') effect of IAI of placebo on the synovium, while acknowledging that our observations may partly reflect natural variances in synovial hypertrophy. Properly powered studies are needed to confirm these findings.