Introduction: Gout affects approximately 15% of Maori and Pacific men, these men being at risk of early onset, severe disease with formation of gouty tophi and joint damage. Gout most frequently affects the foot, particularly the big toe and midfoot. This disease initially presents as self-limiting attacks of severe joint inflammation, and in the presence of persistent hyperuricaemia, tophaceous disease may also develop. Tophi are collections of monosodium urate crystals surrounded by chronic inflammatory cells and connective tissue. Tophi typically occur in both subcutaneous tissues and within affected joints, and may cause pain, cosmetic problems, mechanical obstruction of joint movement, and joint destruction. Despite the predilection of gout to the foot, the impact of gout on foot function is currently unknown and only case studies relating to hallux pain, tibial sesamoid pain and longitudinal tears in peroneal tendons have been reported in the literature. The aim of this study is to assess the intra-tester reliability of certain biomechanical tests to evaluate foot structure and function (plantar pressure measurements, gait parameters, range of motion at the ankle and first MTPJ and the foot posture index) in individuals with gout and to assess the differences between disability, impairment, foot structure and function between individuals with gout and non-gout controls. Subjects: A total of 25 patients with chronic gout with a mean age of 61.2 (11.7) years old were recruited from a rheumatology clinic within the Auckland District Health Board. A further 25 age-and sex-matched controls with a mean age of 57.3 (12.2) years old were recruited from AUT University. Methods: Disability, impairment, foot structure and foot function were assessed for the gout and the control group. Disability and impairment was assessed using the Health Assessment Questionnaire, Foot Function Index, Leeds Foot Impact Scale and Lower Limb Task Questionnaire. Foot structure was investigated using the Foot Posture Index, first metatarsophangeal joint (MTPJ) dorsiflexion, ankle dorsiflexion movement, subtalar joint and midtarsal joint motion, Foot Problem Score, tophi count and muscle strength of extrinsic and intrinsic foot muscles. Foot function was investigated using an in-shoe pressure system measuring mean peak plantar pressures and pressure-time integrals. Temporal-spatial gait parameters were evaluated, as well as peripheral sensation and vibration perception threshold. Plantar pressures were assessed using the Tekscan pressure insole system, gait parameters were measured using the Gaitmat walkway system, peripheral sensation and vibration threshold were assessed using 10gm monofilament and biothesiometer respectively. Intra-tester reliability was investigated using ICC, Standard Error of Measurement and Smallest Real Difference in the gout group for key measures (Foot Posture Index, first MTPJ dorsiflexion, ankle dorsiflexion movement, peak plantar pressures, pressure-time integrals and gait parameters). To investigate the significant difference between the groups, the left and right foot in gout were compared with the left foot of the control group using ANOVA with post-hoc comparisons. Non-parametric tests were used for muscle strength, peripheral sensation and Foot Problem Score and motion at the subtalar and midtarsal joints for comparison between the groups. Walking velocity, cadence and disability and impairment scores between the groups were assessed using an independent t-test with 95% confidence intervals. Significance for all these measures was set to 0.05 except for Chi square where a significance of 0.02 was set. Results: The ICC for the intra-tester reliability was excellent with low measurement error for the measured outcomes. The gout group recorded significantly higher disability and impairment scores than controls (p<0.01). Significant differences between the two groups were recorded for vibration pressure threshold, muscle strength, Foot Problem Score, first MTPJ dorsiflexion, foot motion and gait parameters (p<0.05). Significant differences were demonstrated under the toes for mean plantar pressures and under the lateral heel, midfoot and hallux regions for pressure-time integrals in the gout cases (p<0.05). Conclusions: Individuals with gout have reduced quality of life due to greater disability and impairment. The gouty foot is slightly supinated with reduced dorsiflexion at the first MTPJ. Rearfoot and forefoot motions are limited with a high incidence of digital deformities and dermatological lesions. The foot function in gout is characterized by reduced walking velocity, cadence, step and stride length. The plantar pressures are reduced under the toes with increased duration of loading under the hallux, lateral heel and midfoot regions. Further research using three-dimensional gait analysis is recommended to quantify motion at the foot and ankle joints and also to ascertain the role of proximal joints. Future work could be undertaken to evaluate the impact of acute gout on objective measures of foot function, and to determine predictors of poor foot function in patients with this disease. This will allow further work to investigate or formulate a podiatric management plan in conjunction with pharmacological therapy to improve impairment, disability and function in chronic gout.

OBJECTIVE: Our aim in this study to determine if serum uric acid level measured at baseline is a risk factor to develop Myocardial Infarction among people diagnosed with gout. METHOD: This was a retrospective cohort study, which used the THIN (The Health Improvement Network), an electronic medical records database from the UK. Obtained were SUA level at baseline after gout diagnosis and follow-up till time of event. We performed Cox proportional hazard regression models to examine the relation of SUA levels to risk of incident MI for men and women separately, and the multivariable regression model. RESULTS: There were 12,180 individuals included in this study, of them, 70% (n=8539) were men. There were 200 events of MI, 145 in men and 55 in women. SUA were not associated with risk of MI in unadjusted and adjusted multivariable regression model, the crude HR of MI in men were 1.27 (95% CI: 0.70-2.30), 0.97 (95% CI: 0.56-1.69), 0.83 (95% CI: 0.47-1.46), and 1.07 (95% CI: 0.62-1.84), respectively, for each increased SUA categories. No change observed after full adjustment. Similar results were also observed in women. CONCLUSION: There is no association between baseline SUA and risk of MI among gout patients.

Conselho Nacional de Desenvolvimento Científico e Tecnológico / Gout is characterized by the deposition of monosodium urate (MSU) crystals. Despite being one of the most painful forms of arthritis, gout and the mechanisms responsible for its acute attacks are poorly understood. In the present study, we found that MSU caused dose-related nociception (DE50=0.04 (0.01-0.11) mg/paw) and edema (DE50=0.08 (0.04-0.16) mg/paw) when injected into the hind paw of rats. Treatment with the selective TRPV1 receptor antagonist SB366791 largely inhibited nociceptive and edematogenic responses to MSU. Moreover, the desensitization of capsaicin-sensitive afferent fibers as well as the pretreatment with the tachykinin NK1 receptor antagonist RP 67580 also significantly reduced MSU-induced nociception and edema. Once MSU was found to induce mast cell stimulation, we investigated the participation of these cells on MSU effects. Prior degranulation of mast cells by repeat treatment with compound 48/80 decreased MSU-induced nociception and edema or histamine and serotonin levels in the injected tissue. Moreover, pretreatment with the mast cell membrane stabilizer cromolyn effectively inhibited nociceptive and edematogenic responses to MSU. MSU induced a release of histamine, serotonin and tryptase in the injected tissue, confirming mast cell degranulation Furthermore, the antagonism of histaminergic H1 and serotoninergic receptors decreased the edema, but not the nociception, of MSU. Finally, the inhibition of tryptase activity was capable of largely reducing either MSU-induced nociception or edema. Collectively, the present findings demonstrate that MSU produces a nociceptive and edematogenic response mediated by TRPV1 receptor activation and mast cell degranulation. / A gota é caracterizada pela deposição de cristais de urato monossódico (MSU) nas articulações. Apesar de ser um dos mais dolorosos tipos de artrite, os mecanismos responsáveis pela indução da dor durante os ataques agudos de gota são pouco entendidos. No presente estudo, objetivamos investigar o papel do receptor TRPV1 na nocicepção e edema induzidos por cristais de MSU em ratos. Assim, demonstramos que o MSU causa nocicepção (DE50=0.04 (0.01-0.11) mg/pata) e edema dependentes da dose (DE50=0.08 (0.04-0.16) mg/pata) quando injetado na pata dos ratos. O tratamento com o antagonista seletivo do receptor vanilóide TRPV1 SB 366791 inibiu significativamente as respostas nociceptiva e edematogênica causadas pelo MSU. De maneira semelhante, a dessensibilização de fibras aferentes sensíveis a capsaicina bem como o tratamento com o antagonista do receptor para taquicinina NK1 RP67580 também reduziram significativamente a nocicepção e o edema induzidos pelo MSU. Sabendo que estudos prévios demonstraram que MSU induz a estimulação de mastócitos, nós investigamos a participação destas células nos efeitos do MSU. A desgranulação prévia de mastócitos por tratamento repetido com o composto 48/80 reduziu a nocicepção e o edema induzidos pelo MSU assim como os níveis de histamina e serotonina no tecido injetado. Adicionalmente, o tratamento com o estabilizador de membrana de mastócitos cromolina, reduziu efetivamente as respostas nociceptivas e edematogênicas ao MSU. A administração de MSU induziu a liberação de histamina, serotonina e triptase no tecido injetado, confirmando a desgranulação mastocitária. Além disso, o antagonismo de receptores histaminérgicos H1 e serotoninérgicos, reduziram o edema, mas não a nocicepção causados pelo MSU. Finalmente, a inibição da atividade da triptase foi capaz de reduzir amplamente a nocicepção e o edema induzidos pelo MSU. Coletivamente, nossos resultados demonstram que o MSU produz uma resposta nociceptiva e edematogênica mediada pela ativação do receptor TRPV1 e pela desgranulação de mastócitos.

Introduction: Gout is a painful form of acute inflammatory arthritis associated with elevated uric acid crystal deposition especially in the joints, but also in tendons and the kidney. Between 1 and 2% of Western populations are affected and in severe cases, gout sufferers can be completely incapacitated. Despite the number of gout sufferers, the high number of risk factors and high incidence of adverse drug reactions using the standard treatment regimens, little research involving gout has been done within the highly diverse multiracial and multicultural population of South Africa. Hypothesis: This study was a hypothesis generating observational study to assess whether serum levels of pro-inflammatory cytokines and acute phase protein levels could be used as markers of the gout status of a patient. Method: Thirty gout patients were enrolled onto the study and attended two visits. At the screening visit; medical history, vital signs and demographic details were collected from intercritical gout patients. At both visits, patients completed visual analogue scales; namely: subject’s assessment of pain and subject’s assessment of disease activity. A doctor completed the physician’s assessment of disease activity at both of the visits. At the end visit, patients experiencing an acute gout attack were asked to list various foods and beverages that triggered said attacks. Patients were requested to return for their second visit as soon as they experienced a gout attack, however, those patients that did not experience a gout attack were asked to return to the clinic to complete the follow up visit four months after their baseline visit. Uric acid, IL-1β, TNF-α and CRP were measured for each patient at both visits. Results: Many of the patients displayed risk factors for metabolic syndrome. The mean subject’s assessment of pain score increased from 31mm at the screening visit to 40mm at the end visit (p=0.1947; n=26), while the mean subject’s assessment of disease activity score and the mean physician’s assessment of disease activity increased from 30mm to 37mm (p=0.3196; n=26) and 23mm to 35 mm (p=0.0937; n=26) respectively. Uric acid levels decreased from 1.053mmol/L to 0.871mmol/L between visits (p=0.0926; n=25) while CRP concentrations increased significantly from 10.2mg/L to 26.6mg/L (p=0.0278, n=24). IL-1β concentrations remained similar (12.17pg/ml to 12.54pg/ml) while TNF-α concentrations decreased from 12.63pg/ml to 3.54pg/ml, however neither of these were statistically significant differences. Upon stratifying results into active and non-active patients, both IL-1β and TNF-α concentrations decreased between non-active and active patients, while CRP and urate concentrations increased. However, none of these differences were statistically significant. Conclusion: The visual analogue scales all showed an increase between the screening and final visits, although this was not statistically significant. Uric acid concentrations decreased between visits, however this increase was once again not statistically significant. There appears to be no association between inflammatory markers and the level of gout activity, although this needs to be tested in a larger sample population. Results in South African patients have confirmed results from previous studies where gout patients are at a higher risk of metabolic syndrome than the normal population. Copyright / Dissertation (MSc)--University of Pretoria, 2011. / Pharmacology / unrestricted

1 ABSTRACT Lorencová Š.: Nutraceuticals: possibilities in decreasing of hyperuricemia and alleviating gout. Diploma thesis, Charles University in Prague, Faculty of Pharmacy in Hradec Kralove, Department of Pharmaceutical Botany and Ecology, Hradec Kralove 2020, 82 p. This research work was conducted on the basis of literature analysis, reviewing papers mainly from international but also domestic journals. The review describes pathophysiology of gout and discusses options to mitigate the disease with the aid of dietary supplements. This work presents symptoms and a clinical picture of the disease as well as its origin and risk factors, pathological processes leading to the development of the disease, and a short overview of current pharmacotherapy. Furthermore this work summarises natural substances including plant extracts that may be utilised in the prevention and support of gout treatment. In particular, these include vitamins, unsaturated fatty acids, polyphenols and peptides. This work also describes plants used in the traditional treatment of gout and gives a brief overview of natural substances including plant extracts contained in food supplements that are available on the market in Czech Republic. This work also describes the role of purines, fructose, alcoholic drinks and tomatoes in triggering...

Introduction Severe hypercalcemia from chronic gout is a rare phenomenon seen after the advent of newer drugs for its treatment. The hypercalcemia is secondary to either granuloma formation around the tophi or chronic immobilization from severe gouty arthritis. We present a patient with chronic tophaceous gout presenting with severe hypercalcemia and acute kidney injury. Case presentation A 63-year-old male patient with a past medical history of hypertension and chronic gout presented to the office with chronic, severe left knee pain. Initial evaluation of the knee with X-rays revealed destruction of the knee joint with cystic changes, and subsequent MRI with contrast showed soft tissue mass in the suprapatellar pouch with intraosseous extension and involvement of medial and lateral collateral ligament involvement. After interdisciplinary evaluation between radiology, orthopedic surgery, and oncology, this was concerning for highly aggressive pigmented villonodular synovitis of the knee, and a decision was made for the patient to undergo complete knee replacement. Perioperative workup was significant for severe hypercalcemia with a total calcium level of 13.2 mg/dl with ionized calcium of 7.2 mg/dl. Further evaluation into the cause of hypercalcemia revealed a low normal intact parathyroid hormone (PTH) level with normal phosphorus, calcidiol, and calcitriol levels. Other etiologies of hypercalcemia such as multiple myeloma, malignancies, metastatic disease, autoimmune, granulomatous, and infectious processes are excluded with extensive workup. The hypercalcemia is treated with fluids, diuretics, and bisphosphonates, eventually normalizing the calcium levels. The patient underwent total left knee replacement, and the mass identified was sent for biopsy. Biopsy revealed a prominent granulomatous reaction to amorphous crystals containing birefringent crystals under polarised light. Uniquely during our evaluation, vitamin D metabolites, uric acid, and PTH levels were normal despite the biopsy findings. The patient's calcium continued to be normal (8.4 to 10.4 mg/dl) over six months after the surgery. Thus, the scenario is supportive of hypercalcemia secondary to granulomatous inflammation around the large tophi. Conclusion Although rare, the knee joint is a site of severe tophaceous gout, and deposition of uric acid crystals can invoke a granulomatous reaction presenting with severe hypercalcemia as in our patient. Unique to our case, the patient can have benign lab findings on evaluation of hypercalcemia. Only a few case reports are illustrated in the literature, making our case and patient presentation unique.

There are localised proteins (so-called urate transporters) in the renal proximal tubules and in the intestine, which excrete and reabsorb uric acid. Polymorphisms in the genes coding these proteins can result in the disruption of the transport function and development of hyperuricemia and gout. However the serum level of uric acid is also determined by other factors which include the intake of exogenous purines in food, synthesis of endogenous purines and degradation of nucleic acids, but also certain conditions. In 250 patients with primary hyperuricemia and gout we used Sanger sequencing to analyse the exons and adjacent intron regions in ten genes coding urate transporters: ABCG2, ABCC4, SLC2A9, SLC22A12, SLC22A11, SLC22A13, SLC17A1, SLC17A3, SLC22A6 and SLC22A8. We examined a possible connection between the identified genetic variants and primary hyperuricemia and gout based on a comparison of allele frequencies with the European population, according to topological models, according to programs predicting the functional impacts of variants and searches in specialised literature. We also took into account the conclusions of functional studies analysing the impact of nonsynonymous variants in the ABCG2 and SLC2A9 genes. We also focused on the effect of the concomitant occurrence of several...

No / Gout is a disease caused by the abnormal accumulation of uric acid in the body, which can result in sodium urate crystals forming tophi at joints, with associated erosion of bone and cartilage. Only two examples of tophi have been reported from archaeological individuals, and the diagnosis of gout based on dry bone manifestations can be difficult. This paper presents preliminary results of a new technique to aid the diagnosis of gout in palaeopathology, namely high performance liquid chromatography (HPLC). Five archaeological skeletons with suspected gout (diagnosed using visual and radiological analysis) and three controls were analysed. Two of the gouty individuals had a white powder in their erosive lesions. HPLC showed the presence of uric acid in bone in four of the five individuals with evidence of gouty arthritis and was negative for uric acid in bone from the three controls. The white powder was also positive for uric acid. With reliance on the presence of articular erosions, cases of gout will be missed in archaeological human bone. HPLC measurement of uric acid could prove useful in the differential diagnosis of erosive arthropathy in archaeology. It may also be useful in identifying individuals with an increased body pool of uric acid, linked to conditions included in the term `metabolic syndrome¿. As a result, HPLC uric acid measurement also has the potential to provide additional information on health and lifestyle in past communities.

Conselho Nacional de Desenvolvimento Científico e Tecnológico / The gout is an extremely painful type of arthritis. Despite the large number of drugs available for its treatment, they usually cause many adverse effects that limit their use. Then, further investigations are necessary for a better understanding the different mechanisms involved in gout. It was found previously that TRPV1 receptor, an ion channel modulated by various inflammatory mediators mediated edema and the nociceptive responses induced by subcutaneous injection of MSU in rats. In this plantar model, activation of TRPV1 depended largely on the activation of mast cells. Since the environments articular broadly differ as their cellular constituents, questioned the involvement of this receptor in a more reliable model with this clinical arthropathy. The aim of this study was to investigate the role of TRPV1 in a model of acute gout induced by intra-articular administration (i.a.) of crystals of monosodium urate (MSU) tíbio-tarsal articulation rats. It was observed that the antagonism of the TRPV1 receptor (by the selective antagonist SB366791), systemic knockdown (caused by treatment with resiniferatoxin subcutaneous injection a TRPV1 agonist) or axonal silencing (perineural injection a combination of capsaicin and QX-314) sensory fibers TRPV1-positive significantly prevented the pain-related behaviors (spontaneous nociception, heat hyperalgesia, and mechanical allodynia) and inflammation (edema, plasma extravasation, leukocyte infiltration and IL - 1β ) was caused by the administration of MSU. Additionally, we observed a significant increase in immunoreactivity of TRPV1 in articular tissue 4 hours after administration of MSU. Subsequently, we investigated the possibility role of NO, an endogenous activator of TRPV1 in this model. The administration of MSU induced an increase in the production of stable metabolites (NOx) emissions of nitric oxide (NO) exudates in the joint, which was inhibited by a selective inhibitor of nitric oxide synthase (NOS). In addition, the non-selective NOS inhibitor prevented the spontaneous nociception, edema and plasma extravasation, and leukocyte infiltration after MSU injection. Moreover it was found that the administration of a NO donor induced heat hyperalgesia and spontaneous nociception, but not mechanical allodynia and edema. The TRPV1 receptor antagonism prevented only the edema caused by that donor. Thus, these results suggest that TRPV1 plays a role in the development and maintenance of nociceptive and inflammatory responses triggered in the model of acute articular gout, but only edematogenic response appears to be mediated by TRPV1 activation by NO. / A gota é um tipo de artrite extremamente dolorosa. Apesar do grande número de fármacos disponíveis para seu tratamento. Muitos causam efeitos adversos que limitam seu uso. Maiores investigações são necessárias para um melhor entendimento dos diferentes mecanismos envolvidos na gota. Verificou-se previamente que o receptor TRPV1, um canal iônico modulado por vários mediadores inflamatórios, mediou as respostas nociceptiva e edematogênica induzidas pela injeção subcutânea de MSU em ratos. Neste modelo plantar, a ativação do TRPV1 dependeu amplamente da ativação de mastócitos. Sendo o ambiente articular amplamente diferenciado quanto a sua constituição celular, questionou-se o envolvimento deste receptor em um modelo mais fidedigno com a clínica dessa artropatia. O objetivo deste estudo foi investigar o papel do TRPV1 em um modelo de gota aguda, induzida pela administração intra-articular (i.a.) de cristais de urato monossódico (MSU) na articulação tíbio-tarsal de ratos. Observou-se que o antagonismo do receptor TRPV1 (pelo antagonista seletivo do receptor TRPV1 SB366791), a desfuncionalização sistêmica (causada pelo tratamento subcutâneo com resiniferatoxina) ou o silenciamento axonal (com a combinação periciática de capsaicina e QX 314) das fibras sensoriais TRPV1-positivas preveniram significativamente os comportamentos relacionados à dor (nocicepção expontânea, hiperalgesia ao calor e alodínea mecânica) e à inflamação (edema, extravasamento plasmático, infiltração de leucócitos e produção de IL-1β) causadas pela administração i.a. de MSU. Adicionalmente, observou-se um aumento expressivo da imunoreatividade do TRPV1 no tecido articular 4 horas após a administração do MSU. Posteriormente investigou-se a possibilidade do NO ser um ativador endógeno do TRPV1 neste modelo. Demonstrou-se que a administração i.a. de MSU induziu um aumento na produção de metabólitos estáveis (NOx) do óxido nítrico (NO) nos exsudatos articulares, o qual foi inibido pela administração i.a. de um inibidor não seletivo da óxido nítrico sintase (NOS). Além disso, o inibidor não seletivo da NOS preveniu a nocicepção espontânea, o edema e também o extravasamento plasmático, a infiltração de leucócitos. Por outro lado constatou-se que a administração i.a. de um doador de NO induziu nocicepção espontânea e hiperalgesia ao calor, mas não alodínea mecânica ou edema. O antagonismo do receptor TRPV1 preveniu somente o edema causado por esse doador. Assim, estes resultados sugerem que o TRPV1 exerce um papel relevante no desenvolvimento e manutenção das respostas nociceptiva e inflamatória desencadeadas no modelo articular de crise aguda de gota, porém, apenas a resposta edematogênica parece ser mediada pela ativação TRPV1 através do NO.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Gout is a prevalent form of inflammatory arthritis, which leads to patients poor quality of life. Acute gout attacks produce severe joint pain and inflammation associated with oxidative stress induction. This pathology is provoked by the accumulation of monosodium urate (MSU) crystals, but the underlying pain mechanisms in acute gout attacks are still poorly understood. The transient potential receptor ankyrin 1 (TRPA1) is a sensor for endogenous oxidant compounds, such as hydrogen peroxide (H2O2), found in peptidergic sensory fibers associated to inflammatory pain. The goal of this study was to explore the TRPA1 role in two models of monosodium urate (MSU) crystals-induced inflammation and nociception in rats and mice. We found that TRPA1 antagonism (HC-030031 or camphor), TRPA1 gene deletion or defunctionalization by capsaicin pretreatment of peptidergic TRPexpressing primary sensory neurons markedly decreased MSU-induced nociception and edema after intraplantar (i.pl.) or intra-articular (i.a.) injection. In addition to these neurogenic effects, MSU increased H2O2 levels in the injected tissue, an effect that was abolished by the H2O2-detoxifing, catalase enzyme. TRPA1 immunoreactivity in sciatic nerve and the levels of calcitonin gene related peptide (CGRP) in the synovial tissue were also increased by MSU. H2O2 i.pl. or i.a. injection mimicked MSU, causing nociception and edema prevented by TRPA1 antagonism. Moreover, TRPA1 blockage abrogated the increase in neutrophil infiltration and interleukin-1β elicited by MSU. Our results suggest that MSU-injection increases tissue H2O2 thereby stimulating TRPA1 on sensory nerve endings to produce inflammation and nociception. Thus, TRPA1 may be explored as a valuable target in acute gout management. / A gota é uma forma prevalente de artrite inflamatória que reduz a qualidade de vida dos pacientes. Os ataques agudos de gota produzem dor articular grave e inflamação que são associadas à produção de estresse oxidativo. Esta patologia é provocada pela deposição de cristais de urato monossódico (MSU), mas os mecanismos relacionados à dor observada nos ataques agudos de gota ainda são pouco esclarecidos. O receptor de potencial transitório anquirina 1 (TRPA1) é um sensor para compostos oxidantes, como o peróxido de hidrogênio (H2O2), encontrado em fibras sensoriais peptidérgicas e este está relacionado ao desenvolvimento de dor inflamatória. O objetivo deste estudo foi avaliar o papel do receptor TRPA1 em dois modelos de inflamação e nocicepção induzidos pela administração de cristais de MSU em ratos e camundongos. Observamos que o antagonismo do receptor TRPA1 (HC-030031 ou cânfora), a deleção genética deste canal, ou ainda a indução de dessensibilização dos neurônios sensoriais que expressam os receptores TRP pelo tratamento com capsaicina reduziram marcantemente a nocicepção e edema induzido pela administração intraplantar (i.pl.) ou intra-articular (i.a.) dos cristais de MSU. Além destes efeitos neurogênicos a administração de MSU aumentou o conteúdo de H2O2 nos tecidos injetados, um efeito que foi bloqueado pela enzima catalase, e também aumentou a imunoreatividade para o receptor TRPA1 no nervo ciático e no tecido sinovial, e também os níveis do peptídeo relacionado ao gene da calcitonina (CGRP) no tecido sinovial. A administração de H2O2 por via i.pl. ou i.a. induziu efeitos semelhantes àqueles induzidos pela administração de MSU, e estes foram reduzidos pela administração de antagonistas TRPA1. Ainda, o bloqueio do receptor TRPA1 reduziu a infiltração de neutrófilos e a produção de interleucina 1β induzidas pela administração de cristais de MSU. Em conclusão, os nossos resultados sugerem que a administração dos cristais de MSU é capaz de aumentar a produção de H2O2 que então poderia estimular o receptor TRPA1 expresso em neurônios sensoriais causando nocicepção e inflamação dos tecidos. Dessa maneira, o canal TRPA1 poderia ser explorado como um alvo em potencial para o tratamento dos ataques agudos de gota.