Why Patients with Early RA Have Pain

This report is a brief synopsis of the first part of the year in review presented by Ingred Lundberg from the Karolinska Institute.

There has been a shift in the research focus in RA from established disease to pre-disease. EULAR has proposed six phases of RA development:

Phase A: Genetic Risk Factors
Phase B: Environmental Risk Factors

Localized Autommunity

Phase C: Systemic Autoimmunity
Phase D: Symptoms without Arthritis

Imaging U/S, MRI Abnormalities

Phase E: Undifferentiated Arthritis
Phase F: Established RA.

The question is, how can we identify individuals at risk to develop RA?

The first topic questioned the use of imaging in predicting progression of pre-clinical disease. The initial study highlighted the use of ultrasound (US) in ACPA-positive individuals without clinical synovitis. Not surprisingly, in those patients without synovitis on US, the time to develop arthritis was longer than those with synovitis on US. The other study used MRI in patients with clinical suspect arthralgia. Positive MRI was highly predictive of onset of clinical RA.

The second topic looked at autoantibodies and induction of pain in pre-clinical RA. This is a very interesting topic because how many times have we seen patients with positive RF/ACPA without discernible synovitis complain of diffuse pain and stiffness? It turns out there may be a biological basis to this.

It has been shown that ACPA can actually bind and activate osteoclasts. This induces the release of IL-8 from the osteoclasts. The IL-8 acts on nociceptors resulting in pain. It has been shown that ACPA induces pain behaviour in mice without joint inflammation. It seems that these pain mechanisms are actually dependent on IL-8 released by osteoclasts localized near nerves. Interestingly, IL-8 blockade in ACPA injected mice prevents both bone destruction and pain. Wow. There will definitely be more on this topic.

More reports from ACR 2016