Beyond urate lowering: Analgesic and anti-inflammatory properties of allopurinol

The management of gout consists of urate-lowering therapy and acute and chronic anti-inflammatory drugs. Allopurinol, a xanthine oxidase inhibitor, is the primary urate-lowering therapy employed for decades. Recent studies suggest cardiovascular disease and mortality, chronic kidney disease, prostate cancer, and manic symptoms are reduced in patients with gout treated with allopurinol. These findings support that allopurinol contributes to a variety of beneficial effects beyond urate lowering. This manuscript reviews the analgesic and anti-inflammatory properties of allopurinol, which are rarely discussed. Several mechanisms are suggested to confer these benefits including accumulation of adenosine and inhibitory effects of allopurinol on reactive oxygen species, tumor necrosis factor- α, nuclear factor kappa-light-chain-enhancer of activated B cells, and the NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome. Also, allopurinol blocks the stimulating effects of thioredoxin-interacting protein and interacts directly with the redox-active domain of thioredoxin as a negative regulator, decreasing NLRP3 activation. The importance of allopurinol's analgesic and anti-inflammatory properties requires further study and the implications to patient care better understood.