Participation of the TRPV1 receptor in the development of acute gout attacks

Abstract

Objective: The aim of the present study was to investigate the participation of TRPV1 in an acute gout attack model.

Methods: Experiments were conducted to evaluate the participation of TRPV1 in the nociceptive and inflammatory responses (oedema, plasma extravasation, leucocyte infiltration and also IL-1β production) triggered by IA (ankle) administration of monosodium urate (MSU) in rats using selective antagonist TRPV1 receptor, defunctionalization of sensory fibres and increased immunoreactivity. We have also analysed the inflammatory response. The participation of mast cells in the MSU-induced nociception and inflammation was evaluated using a mast cell stabilizer and a mast cell degranulator compound.

Results: We observed that MSU (1.25 mg/site) injected into the rat ankle joint elicited ongoing pain-like behaviour, hyperalgesia, allodynia and articular oedema as well as plasma extravasation, leucocyte infiltration and IL-1β production in lavage fluid. All of these events were inhibited by the co-administration of the selective TRPV1 receptor antagonist SB366791 (10 nmol/site). MSU crystals also increased the immunoreactivity of the TRPV1 receptor in the articular tissue of injected animals. Furthermore, the defunctionalization of TRPV1-positive sensory neurons also significantly reduced MSU-induced ongoing pain-like behaviour, hyperalgesia and oedema.

Conclusion: Thus we demonstrate that TRPV1 acts on sensory neurons and plays a relevant role in the nociception and inflammation induced by IA MSU, indicating it as a potential target to treat acute gout attacks.

Keywords: TRPV1 antagonist; arthritis; mast cell; sensory neuron; vanilloid receptor.