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Background There is a growing search for therapeutic targets in the treatment of gout. The present study aimed to evaluate the analgesic and anti-inflammatory potential of angiotensin type 2 receptor (AT 2 R) antagonism in an acute gout attack mouse model. Methods Male wild type (WT) C57BL/6 mice either with the AT 2 R antagonist, PD123319 (10 pmol/joint), or with vehicle injections, or AT 2 R KO mice, received intra-articular (IA) injection of monosodium urate (MSU) crystals (100 μg/joint), that induce the acute gout attack, and were tested for mechanical allodynia, thermal hyperalgesia, spontaneous nociception and ankle edema development at several times after the injections. To test an involvement of AT 2 R in joint pain, mice received an IA administration of angiotensin II (0.05–5 nmol/joint) with or without PD123319, and were also evaluated for pain and edema development. Ankle joint tissue samples from mice undergoing the above treatments were assessed for myeloperoxidase activity, IL-1β release, mRNA expression analyses and nitrite/nitrate levels, 4 h after injections. Results AT 2 R antagonism has robust antinociceptive effects on mechanical allodynia (44% reduction) and spontaneous nociception (56%), as well as anti-inflammatory effects preventing edema formation (45%), reducing myeloperoxidase activity (54%) and IL-1β levels (32%). Additionally, Agtr2 tm1a mutant mice have largely reduced painful signs of gout. Angiotensin II administration causes pain and inflammation, which was prevented by AT 2 R antagonism, as observed in mechanical allodynia 4 h (100%), spontaneous nociception (46%), cold nociceptive response (54%), edema formation (83%), myeloperoxidase activity (48%), and IL-1β levels (89%). PD123319 treatment also reduces NO concentrations (74%) and AT 2 R mRNA levels in comparison with MSU untreated mice. Conclusion Our findings show that AT 2 R activation contributes to acute pain in experimental mouse models of gout. Therefore, the antagonism of AT 2 R may be a potential therapeutic option to manage gout arthritis.

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