THE MECHANISMS BEHIND GOUT ATTACK PAIN AND RESOLUTION

WITH PROFESSOR GEORG SCHETT, MD

TRANSCRIPT

Pain is instigated largely by inflammatory mediators. I think that is a key issue. One has to think that gout is a very innate immune system-driven process.

Uric acid crystals bind a lot of sodium. When the crystal is taken up by an immune cell, all the sodium is also taken up.

Which leads to the influx of water into the cell and a so-called cell swelling. So, this swelling provokes one important thing. When the water comes in, it dilutes other ions in the cell.

And the most important ion in a cell is potassium. And potassium concentration, because of the water influx, decreases, and this decrease of potassium is the key trigger for the activation of a machinery in the cell, which is called the inflammasome.

And the inflammasome produces a lot of interleukin 1, and as you know, interleukin 1 is the key cytokine involved in gout.

Prostaglandins, which are released by local immune cells, allow vasodilation to increase blood vessels. They are all cytokines that have an enormous capacity to induce pain by peripheral sensitization of nerve fibers. These cytokines then attract more and more neutrophils.

When a neutrophil engages a crystal, the neutrophils die by a specific form of cell death, which is called NETosis. That stands for neutrophil extracellular trap formation.

Neutrophils are short-lived cells. When they die, they exit their DNA, and that is kind of a glue for the crystals.

And these aggregated nets are actually the way to resolve inflammation. aggNETs cleave inflammatory cytokines, reduce local concentrations of the inflammatory cytokines, and thereby also stop the pain response.

BoneBoneBone

THE INTERACTION BETWEEN aggNETs AND BONE

Professor Nicola Dalbeth, MD examines the relationship between tophi and bone erosion in gout.

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WHAT YOU CAN DO

Learn about a treatment option for chronic gout.

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  1. Schett G, et al. RMD Open. 2015;1:(suppl 1):e000046.