Uric Acid Crystals Research Articles

Recent insights into the pathogenesis of hyperuricaemia and gout

Gout is a common rheumatic disease in humans which is characterized by elevation in serum uric acid levels, and deposition of uric acid crystals in the joint. Hyperuricaemia is the primary risk factor for the development of gout and primates have uniquely high levels of serum uric acid due to missense mutations in the uricase gene. Levels of serum uric acid are known to be highly heritable, and mutations in genes which encode enzymes in the purine salvage pathway have long been recognized as rare causes of gout. Until recently, however, little has been known about the genetic determinants of urate metabolism and susceptibility to gout in the general population. Over recent months, a series of large scale genome wide association studies have been performed which have shed new light on the genes which regulate serum uric acid levels and susceptibility to gout. Most of these genes seem to be involved in regulating the renal excretion of uric acid which underscores the importance of reduced urate excretion as opposed to increased endogenous production as a cause of gout. Further work will now be required to investigate the mechanisms by which these genetic variants regulate urate excretion and serum urate levels. However, it seems likely that the genes so far identified will represent new molecular targets for the design of drugs to enhance urate excretion and the genetic variants that predispose to gout might be of value as genetic markers of susceptibility to gout.

The evolution of gout (an old lifestyle disease)

Background: Few diseases that confront the 21st century clinician have documented history which dates back to early human era. Methods: We reviewed how the understanding of the aetiogenesis, symptomatology, diagnosis and treatment of gout including myths have evolved and discussed the implications thereof. Results: Gout has been recognized as a clinical entity before 2000BC with Hippocrates describing the five aphorism of gout. Between the 1st and the 6th century AD, the role of genetics and the association of gout with an indulgent lifestyle and tophi were described. Hemodactyl (a source of colchicines) was also first identified during this period. “Gout” was coined from the Latin word “Gutta” in the 13th century and the microscopy of uric acid crystals and gout symptomatology were the focus of investigations between the 17th and 18th centuries. Several drug treatments were developed between the 19th and 20th centuries including salicylates, probenecid and allopurinol. Gout as a risk factor for metabolic syndrome, NIDDM and cardiovascular disease is a challenge for the 20th century and the future. Conclusion: The understanding of gout has evolved with human development but the challenges for the future will include how to deal with the associated cardiovascular co-morbidities.

Gout

Because of the changing dietary habits of an aging population, hyperuricemia is frequently found in combination with other metabolic disorders. Longstanding elevation of the serum uric acid level can lead to the deposition of monosodium urate crystals, causing gout (arthritis, urate nephropathy, tophi). In Germany, the prevalence of gouty arthritis is estimated at 1.4%, higher than that of rheumatoid arthritis. There are no German guidelines to date for the treatment of gout. Its current treatment is based largely on expert opinion. Selective literature review on the diagnosis and treatment of gout. Asymptomatic hyperuricemia is generally not an indication for pharmacological intervention to lower the uric acid level. When gout is clinically manifest, however, acute treatment of gouty arthritis should be followed by determination of the cause of hyperuricemia, and long-term treatment to lower the uric acid level is usually necessary. The goal of treatment is to diminish the body's stores of uric acid crystal deposits (the intrinsic uric acid pool) and thereby to prevent the inflammatory processes that they cause, which lead to structural alterations. In the long term, serum uric acid levels should be kept below 360 micromol/L (6 mg/dL). The available medications for this purpose are allopurinol and various uricosuric agents, e.g., benzbromarone. There is good evidence to support the treatment of gouty attacks by the timely, short-term use of non-steroidal anti-inflammatory drugs (NSAID), colchicine, and glucocorticosteroids.

A novel role for uric acid in acute kidney injury associated with tumour lysis syndrome

Tumour lysis syndrome (TLS) is a complication associated with the treatment of tumour types with high proliferative rate, large tumour burden or high sensitivity to cytotoxic therapy. The implementation of risk stratification strategies [1], appropriate prophylactic measures, vigilant monitoring of laboratory parameters and active interventions to reduce risk factors has dramatically decreased the incidence of clinically significant morbidity that results in end organ damage and mortality. Despite these advances, 5–6% of atrisk paediatric and adult patients undergoing chemotherapy develop acute kidney injury (AKI), and 40–50% of these patients will require dialysis therapies with associated allcause mortality in excess of 50% [2–4]. Similar outcomes are reported with spontaneous TLS [5]. The lack of standardized definitions and outcome measures has hampered appreciation of the extent of adverse renal outcomes in TLS. Recent adoption of a uniform definition of AKI (increase in serum creatinine of 0.3 mg/dL from baseline or a 50% increase in serum creatinine from baseline values within 48 h) [6] and the recognition that the development of in-hospital AKI have significant implications for long-term mortality [7] underscores the need to understand the mechanisms involved in AKI associated with TLS. Furthermore, the effect of chronic kidney disease (CKD) on renal outcomes in TLS requires a study, as clinical tumour lysis occurs more frequently in patients with pretreatment renal impairment [8]. One study examining risk factors for in-hospital AKI of diverse aetiologies reported that CKD increases the risk of AKI 40-fold with a 20-fold increased risk for dialysis [9]. Here, we will briefly review the current understanding of the pathogenesis of TLS-induced AKI. In particular, a recent literature suggests that AKI and nephropathy are not simply due to intrarenal crystal deposition of urate and phosphate. Mechanism of AKI associated with intrarenal deposition of uric acid crystals TLS is a group of metabolic complications that occur after the treatment of large volume, rapidly proliferating haematological cancers including not only acute leukaemia and aggressive lymphomas but also some solid tumours. Metabolic alterations that result include hyperkalaemia, hyperphosphataemia, hyperuricaemia and hyperuricosuria, hypocalcaemia and consequent AKI. Specifically, AKI associated with TLS has been considered to be exclusively a crystal-dependent process caused by the massive and abrupt release of intracellular metabolites from chemosensitive, rapidly proliferating tumour cells that undergo rapid lysis and release nucleic acid breakdown products, phosphorus and potassium. Both urate and calcium phosphate crystals may cause crystal-dependent injury of the kidney which overwhelms the normal homeostatic mechanism(s) autoregulating normal renal physiology [10]. One of the most important mediators of AKI resulting from TLS is uric acid. When dying cells release DNA and RNA, they are degraded in the liver and other sites with the rapid production of uric acid. Serum uric acid rises acutely, resulting in marked uricosuria. Such cell death and degradation also results in acid generation, often with volume depletion, resulting in acidic urine that decreases the solubility of uric acid. When levels of urinary uric acid exceed its solubility, both micro- and macrocrystal formations occur in the distal tubules and collecting ducts with obstruction of the tubular lumen. The prevention of AKI resulting from TLS includes initiating prophylactic measures prior to and during chemotherapy, including hydration, alkalinization of the urine, use of the xanthine oxidase inhibitor allopurinol, as well as the urate oxidase inhibitor, rasburicase or its derivatives.

Gout and Quality of Life: Table 1.

Gout is a common inflammatory arthritis triggered by the crystallization of uric acid within the joints1. Gout causes severe pain and suffering and is a substantial cause of morbidity. Further, emerging evidence suggests that gout is strongly associated with the metabolic syndrome2 and may lead to myocardial infarction3–5, diabetes6, and premature death7,8. A number of epidemiological studies from a diverse range of countries suggest that gout has increased in prevalence and incidence in the past few decades. Using the NHANES III age/sex prevalence and the corresponding 2005 population estimates from the US Census Bureau, it is estimated that up to 6.1 million adults aged ≥ 20 years have ever had gout9. Consequently, gout has a significant economic impact in society due to both direct medical costs and indirect costs9–12. A substantial proportion of gout patients under the care of physicians fail to achieve adequate control of hyperuricemia or symptoms13. Recent studies indicate that the majority of gout patients under the care of physicians are not adequately managed with currently available anti-gout therapies13–17. These gout cases have been referred to as “treatment-failure gout” and have become the primary target for quality improvement of care, including new drug development13,18–23. Although recent treatment guidelines and increased educational efforts could improve the quality of gout care, even under the very best of conditions, between 100,000 and 300,000 in … Address reprint request to Dr. Choi. E-mail: dr.choi{at}yahoo.com Dr. Kim is supported by NIH T32 (AR07442) Training Program in Rheumatic Disease; Dr. Choi served on the advisory board for Takeda and Savient Pharmaceuticals.

Receptor-independent, lipid dependent mechanism of Syk kinase activation in dendritic cells (134.71)

Abstract The binding of antigens to professional antigen-presenting cells (APCs), particularly dendritic cells (DCs), is essential for immune activation. Previously, it was shown that uric acid crystals, the causative agent of gout, were released from dying and injured cells as a "danger signal" to initiate a robust adaptive immune response. But how uric acid crystals lead to APC activation at a molecular level is unknown. Using atomic force microscopy (AFM) to analyze single cell activation in real time, we demonstrate that uric acid crystals directly bind cellular membranes, particularly cholesterol components, with very high affinity. Binding is dependent on intracellular Syk-kinase and PI3-kinase signaling and is independent of extracellular protein receptors. These findings suggest a mechanism that activates the immune system without specific cell surface protein receptors and presents a testable hypothesis for inflammation to materials without evolutionarily sensible receptors such as materials produced post-industrially. This research has applications in vaccine development, biomaterials, inflammation, and crystal-associated arthropathies.

A role of IgM antibodies in monosodium urate crystal formation and associated adjuvanticity (135.71)

Abstract Uric acid is a product of purine metabolism that is secreted from injured or dying cells and can act as an endogenous adjuvant. However, uric acid must crystallize to monosodium urate (MSU) before it can activate dendritic cells and cause gouty inflammation. At normal serum uric acid levels, crystallization of uric acid is not observed in vitro. The crucial question therefore is how the crystals form and cause inflammation. It has been reported that serum from rabbits immunized with MSU, increased uric acid precipitation rates. When C57BL6 or Balb/c mice were immunized with MSU, they produced serum factors which bind to MSU crystals, a phenomenon absent in mu chain deficient IgH (or muMT) mice. These observations show that antibodies may be involved in MSU crystallization. Antibodies produced via B cell hybridomas, were observed to precipitate uric acid in vitro, with the variable region acting as the binding domain. Most importantly, the presence of antibody was instrumental in significantly increasing the basal level of inflammation and mediating the adjuvant effect of uric acid in antigen dependent T cell cytotoxicity in B cell deficient mice. Therefore, we have identified a factor in determining uric acid precipitation and possibly its ability to function as an endogenous adjuvant. This finding suggests a new mechanism of the pathogenesis of gouty arthritis and uric acid induced immune activation.

Uric Acid Is a Danger Signal Activating NALP3 Inflammasome in Lung Injury Inflammation and Fibrosis

Lung injury leads to pulmonary inflammation and fibrosis through myeloid differentiation primary response gene 88 (MyD88) and the IL-1 receptor 1 (IL-1R1) signaling pathway. The molecular mechanisms by which lung injury triggers IL-1beta production, inflammation, and fibrosis remain poorly understood. To determine if lung injury depends on the NALP3 inflammasome and if bleomycin (BLM)-induced lung injury triggers local production of uric acid, thereby activating the NALP3 inflammasome in the lung. Inflammation upon BLM administration was evaluated in vivo in inflammasome-deficient mice. Pulmonary uric acid accumulation, inflammation, and fibrosis were analyzed in mice treated with the inhibitor of uric acid synthesis or with uricase, which degrades uric acid. Lung injury depends on the NALP3 inflammasome, which is triggered by uric acid locally produced in the lung upon BLM-induced DNA damage and degradation. Reduction of uric acid levels using the inhibitor of uric acid synthesis allopurinol or uricase leads to a decrease in BLM-induced IL-1beta production, lung inflammation, repair, and fibrosis. Local administration of exogenous uric acid crystals recapitulates lung inflammation and repair, which depend on the NALP3 inflammasome, MyD88, and IL-1R1 pathways and Toll-like receptor (TLR)2 and TLR4 for optimal inflammation but are independent of the IL-18 receptor. Uric acid released from injured cells constitutes a major endogenous danger signal that activates the NALP3 inflammasome, leading to IL-1beta production. Reducing uric acid tissue levels represents a novel therapeutic approach to control IL-1beta production and chronic inflammatory lung pathology.

A Role of IgM Antibodies in Monosodium Urate Crystal Formation and Associated Adjuvanticity

Uric acid is released from injured cells and can act as an adjuvant signal to the immune system. Uric acid crystals invoke strong inflammatory responses in tissues. Although their biological effects are evident and the associated signaling mechanisms are becoming clear, it remains unexplained as to why uric acid precipitates rapidly in vivo, in sharp contrast to the minimal crystallization in vitro. We report in this study that a group of IgM Abs is able to bind to these crystals, which is interesting in light that B cell-deficient mice do not sense the proinflammatory adjuvant effect of uric acid. The titers of these Abs increase upon immunization with uric acid crystals. We have produced large quantities of such mAbs. The purified IgM Abs can significantly facilitate uric acid precipitation to form the inflammatory crystals in vitro. Infusion of these Abs into B cell-deficient mice significantly increases the basal level of inflammation in these recipients and restores the host's ability to sense uric acid's adjuvanticity. Therefore, we have identified a factor in determining uric acid precipitation and possibly its ability to function as an endogenous adjuvant. This finding suggests a new mechanism of the pathogenesis of gouty arthritis and uric acid-induced immune activation.

Cytology of Synovial Fluid in Gouty Arthritis - Two Cases Report -

Synovial fluid (SF) aspiration cytology is a useful diagnostic tool. For patients with gouty arthritis, the diagnosis is confirmed by the presence of monosodium uric acid (MSU) crystals in the SF, and these crystals are long, pointed ended and needle-shaped and they show strongly negative birefringence. Sometimes, it is difficult to diagnosis between gouty arthritis and other type of inflammatory arthritis. We experienced two unusual cases of gouty arthritis that we performed SF analysis for. The first patient was a 35 year old male who presented with relatively typical clinical symptoms with hyperuricemia, but the SF showed acute inflammatory cells without crystals on light microscopy. Only a few suspected crystals of MSU were identified on polarizing microscopy. The second patient was a 45 year old male who presented with atypical symptoms and pain and swelling of the left ankle and knee joint for 3 weeks. The uric acid level in the serum and urine was increased, but not over the normal limit. However, on light and polarizing microscopy, there were numerous MSU crystals in the SF. Conclusively, in some cases of gouty arthritis, the crystals are not identified on light microscopy or the uric acid level is not dramatically increased. So, the polarizing microscopy, the clinical information and the laboratory findings are all included in the work-up when evaluating the SF cytology of arthritis patients.

Uric Acid Directly Promotes Human T-Cell Activation

BackgroundAbnormally high serum uric acid levels have been associated with several disease conditions including gout and kidney stone disease. More recently, it was shown that uric acid crystals stimulate dendritic cell maturation, activate the NALP3 inflammasome, and enhance antigen-specific immune responses. We hypothesize that uric acid can also stimulate T cells directly and in the absence of antigen presentation. MethodsPurified primary human T cells were incubated with and without uric acid at concentrations of 50, 100, 150, and 200 μg/mL. The expression of T-cell activation markers CD25 and CD70 was assessed by flow cytometry. In other experiments, Jurkat T cells were used and the expression of the costimulatory molecule CD70 was determined at the mRNA level. ResultsUric acid directly activates primary human T cells in the absence of antigen presentation. Furthermore, primary human T cells and Jurkat T cells treated with uric acid overexpress the costimulatory molecule CD70, which plays an important role in T cell-B cell interaction and antibody production. ConclusionsThe finding that uric acid directly promotes T-cell activation in an antigen-independent system is novel and might play a mechanistic role in the inflammatory response observed in gouty arthritis and other immune-mediated diseases.

Herbal remedies used by the rural people of Chhattarpur district, India in the treatment of rheumatism

Rheumatism is a painful joint disease. It is more frequent in female, due to an abnormal uric acid metabolism. The cause is raised serum uric acid level and deposition of uric acid crystal in cartilage of joints, resulting in recurrent attacks of pain and inflammations. Modern medicines do not have any cure for this disease, except their prevention and temporary relief. However, traditional herbal remedies do have a cure. A decoction, oral powder, herbal oil or hot formulation prepared from some household herbs is an excellent remedy for rheumatism, which is discussed in the present paper.

Pathobiology of Inflammation to Cell Death

When a cell dies in vivo the innate immune system investigates the scene of the crime. If the death of the cell is physiological, e.g. as part of normal cell turn over, then the corpse is cleared and little else is done. In fact, as part of this process phagocytes that ingest normal apoptotic cells can actively suppress tissue responses by elaborating anti-inflammatory cytokines (1). However, if the cell has died unexpectedly from some pathological process, then the innate immune system expands its investigation.

“Dangerous Crystals”

Uric acid (UA) crystals are a potent stimulator of inflammation, but how they activate immune cells is not known. In this issue of Immunity, Ng et al. (2008) provide evidence suggesting that UA activates the Syk kinase via membrane cholesterol.

Uric acid is a danger signal activating NALP3 inflammasome in lung injury inflammation and fibrosis

Introduction Lung injury leads to pulmonary inflammation and fibrosis through myeloid differentiation primary response gene 88 (MyD88) and interleukin-1 receptor 1 (IL-1R1) signalling pathway (J Clin Invest, 2007, 117: 3786-3793). However, the molecular mechanisms by which lung injury triggers IL-1β production, inflammation and fibrosis remain poorly understood. Based on the fact that cell/tissue injury and necrosis result in production of uric acid, we hypothesised that uric acid crystals formed at the injury site might represent a key danger signal activating the inflammasome to release IL-1β thereby causing inflammatory lung pathologies. Methods Mice deficient for MyD88, IL-1R1, NALP3, ASC or Casp-1 on C57Bl/6 genetic background were used. Uric acid concentration was determined in bronchoalveolar lavages and lung homogenates. Bleomycin sulfate (10mg/kg) in saline, uric acid or allopurinol crystals (5-50mg/kg) or saline alone were given through the airways by nasal instillation. The number of cells, chemokines, cytokines and TIMP-1 in the bronchoalveolar space and MPO activity in the lung were evaluated. MMP-2 and MMP-9 levels were determined by gelatin zymography. Results Here we show that lung injury depends on the NALP3 inflammasome which is triggered by uric acid locally produced in the lung upon bleomycin-induced DNA damage and degradation. Reduction of uric acid levels using the inhibitor of uric acid synthesis allopurinol or uricase lead to a decrease in bleomycin-induced IL- 1β production, lung inflammation, repair and fibrosis. Further, local administration of exogenous uric acid crystals recapitulates lung inflammation and repair which depend on the NALP3 inflammasome, MyD88 and IL-1R1 pathways, and TLR2 and TLR4 for optimal inflammation, but are independent of the IL-18 receptor. Conclusions Uric acid released from injured cells constitutes a major endogenous danger signal which activates the NALP3 inflammasome leading to IL-1β production. Reducing uric acid tissue levels represents a novel therapeutic approach to control IL-1β production and chronic inflammatory lung pathology.

Receptor-Independent, Direct Membrane Binding Leads to Cell-Surface Lipid Sorting and Syk Kinase Activation in Dendritic Cells

Binding of particulate antigens by antigen-presenting cells is a critical step in immune activation. Previously, we demonstrated that uric acid crystals are potent adjuvants, initiating a robust adaptive immune response. However, the mechanisms of activation are unknown. By using atomic force microscopy as a tool for real-time single-cell activation analysis, we report that uric acid crystals could directly engage cellular membranes, particularly the cholesterol components, with a force substantially stronger than protein-based cellular contacts. Binding of particulate substances activated Syk kinase-dependent signaling in dendritic cells. These observations suggest a mechanism whereby immune cell activation can be triggered by solid structures via membrane lipid alteration without the requirement for specific cell-surface receptors, and a testable hypothesis for crystal-associated arthropathies, inflammation, and adjuvanticity.

Tophi as first clinical sign of gout

Gout results from deposition of monosodium urate crystals in different body tissues, including the skin and soft tissues. With increasing prosperity a rising prevalence of the disease can be observed, especially in highly industrialized countries. Gout can present with acute and painful attacks of arthritis that can affect several joints. In addition, nodular masses of uric acid crystals can develop, which are referred to as tophi. Although tophaceous gout usually is a sign of long during and chronic disease tophi can also occur as first symptom of the disorder. Here, we report on an 85-year-old woman who was diagnosed with tophaceous gout devoid of a prior medical history of the disease.

Parasite eggs in urine cytology: Fact or artifact?

Urine sediment cytology should be done for three main reasons: initial evaluation in symptomatic patients, pursuit of patients with tumoral pathology, and risk population screening. Nevertheless, in the course of microscopic observation it is possible to observe several elements or structures that initially seem unrelated to what we are looking for. Schistosomiasis is an endemic disease affecting humans and animals in tropical countries and the Middle and Far East, but infrequent in the developed countries. Typical eggs from Schistosoma are nonoperculate, embryonated when passed in feces and with transparent shell. The eggs are elongate and large in S. mansoni (114–175 3 40– 70 lm in size), with a prominent lateral spine, and in S. haematobium (112–170 3 40–70 lm) and S. intercalatum (140–240 3 50–85 lm) with a terminal spine. In the cases of S. japonicum (70–100 3 55–65 lm) and S. mekongi (51–78 3 39.66 lm) the eggs are round with a small inconspicuous spine. The presence of miracidium inside the eggs could be a method of differentiation of cytological artefacts in certain clinical settings. Eggs of S. haematobium may also be found in biopsies of the urinary bladder and rectum, and occasionally they may found in feces. Here, we show some structures observed in urinary sediment that because of their morphology, were initially mistaken for parasitic eggs (Schistosoma spp.). The images correspond to voided urine sediment from a 70year-old man presenting hematuria as the only symptom. Biochemical analysis was within normal limits, except for high level of uric acid. Presence of eosinophils in urine and/or eosinophilia was not appreciated. The patient does not report a travel to an area where schistosomiasis is endemic. Figure C-1 shows, against a clear background, and surrounding a small group of urothelial cells, several oval structures (true acid uric crystals) with a spine-like appearance at the ends (thick arrows). The similar unstained and transparent crystals are also observed (thin arrows). In Figure C-2, corresponding to the same sample, three acid uric crystals showed as structures of granular appearance are observed, being the two at the margins with oval shape, 80 3 25 microns in size, and with two spine-like projections at the ends. Figure C-3 shows a true egg of S. haematobium found in human feces (the miracidium can be observed inside of the structure). Because there are few publications relating the presence of S. haematobium eggs in urine sediment, we think that it is easy to mistake or ignore or to fall in the temptation of believing or not. Although schistosomiasis of the urinary bladder is an unusual parasitic infection in our environment, because of the increase in immigration and travel to exotic countries it may be wise to include this disease in asymptomatic hematuria differential diagnosis. The majority of crystals found in urine, except a few such as cystine, tyrosine, and leucine, are of limited clinical value. In many cases, crystals found in urine sediment are not present in the freshly voided specimen, although pH changes and refrigeration are promoters of crystals formation. Uric acid crystals present a variety of shapes such as oval with more or less eroded ends (‘‘lemon-like’’ shape), polygonal, in needles and/or rosettes, etc. Coloration may oscillate between brown-yellow or uncolored, and under polarized light the color variation is quite typical. Nevertheless, because of unusual morphology it may cause false interpretations as it is shown here in inexperienced hands. CF Anatomia Patologica y Citologia, Instituto de Piedras BlancasAsturias, Spain Faculty of Pharmacy, Departament of Parasitology, Universidad de Valencia, Spain Infectious Diseases, Medical Faculty, Ondokuz Mayis University, Samsun, Turkey *Correspondence to: Rafael Martinez-Giron, M.D., Ph.D., Marques de San Esteban, 22-2 B, Gijon 33206, Spain. E-mail: rmartinezgiron@hotmail.com Received 16 January 2008; Accepted 19 July 2008 DOI 10.1002/dc.20940 Published online 30 October 2008 in Wiley InterScience (www. interscience.wiley.com).

Massive uric acid nephrolithiasis with progressive renal failure due to spontaneous tumour lysis syndrome.

Tumour lysis syndrome (TLS) is a constellation of meta- bolic complications due to the rapid destruction of malignant cells, causing renal, cardiac or cerebral dysfunction. Electrolyte abnormalities include hyperuricaemia, hyperphosphataemia, hyperkalaemia and hypocalcaemia. TLS-induced renal failure is mainly caused by uric acid and calcium phosphate crystal deposition and usually develops following cytotoxic chemotherapy. Here, we present a case of spontaneous TLS in a patient with chronic myelomonocytic leukaemia (CMML) with massive uric acid stone and crystal formation and rapidly worsening renal failure. Autopsy revealed underlying tumourous kidney infiltration. Risk factors for occurrence of TLS and current therapeutic management are discussed.

Effect of acute gouty arthritis on sleep patterns: A preclinical study

Background It has been demonstrated that the interrelation between pain and sleep produces changes in sleep patterns and pain perception. Although some evidences suggest that sleep and pain may interact in a complex way, polysomnographic studies in animals with acute nociception are limited in number. Aims This study was carried out in order to evaluate the effect of intra-articular knee injection of uric acid on sleep-wake patterns. Methods Surgical electrode implantation was performed in seven anesthetized Wistar rats to carry out 10 h polysomnographic recordings. Acute nociception was induced by the intra-articular administration of 30% uric acid crystals into the knee joint of the right hind limb. Two recordings before and after intra-articular drug administration were obtained. Sleep-wake parameters were classified as (i) wakefulness (W), (ii) slow wave sleep (SWS), and (iii) rapid eye movement (REM) sleep. Frequency and duration from each parameter were evaluated under the two above-mentioned conditions. Results Intra-articular administration of uric acid induced: (i) an increased duration of wakefulness ( p = 0.014), (ii) a decrement in the duration ( p = 0.001) and number of events ( p = 0.027) in REM sleep, and (iii) a decrement in the total sleep time ( p = 0.001). SWS did not present statistical differences between groups. Conclusions These data suggest that a nociceptive stimulus, induced by the intra-articular administration of uric acid, alters the sleep-wake equilibrium with REM sleep being particularly altered. However, further research concerning pain–sleep interaction is needed.