Objective. Gout is a common cause of inflammatory arthritis and is provoked by the accumulation of monosodium urate (MSU) crystals. However, the underlying mechanisms of the pain associated with acute attacks of gout are poorly understood. The aim of this study was to evaluate the role of transient receptor potential ankyrin 1 (TRPA-1) and TRPA-1 stimulants, such as H 2 O 2 , in a rodent model of MSU-induced inflammation.Methods. MSU or H 2 O 2 was injected into the hind paws of rodents or applied in cultured sensory neurons, and the intracellular calcium response was measured in vitro. Inflammatory or nociceptive responses in vivo were evaluated using pharmacologic, genetic, or biochemical tools and methods.Results. TRPA-1 antagonism, TRPA-1 gene deletion, or pretreatment of peptidergic TRP-expressing primary sensory neurons with capsaicin markedly decreased MSU-induced nociception and edema. In addition to these neurogenic effects, MSU increased H 2 O 2 levels in the injected tissue, an effect that was abolished by the H 2 O 2 -detoxifying enzyme catalase. H 2 O 2 , but not MSU, directly stimulated sensory neurons through the activation of TRPA-1. The nociceptive responses evoked by MSU or H 2 O 2 injection were attenuated by the reducing agent dithiothreitol. In addition, MSU injection increased the expression of TRPA-1 and TRP vanilloid channel 1 (TRPV-1) and also enhanced cellular infiltration and interleukin-1 levels, and these effects were blocked by TRPA-1 antagonism.Conclusion. Our results suggest that MSU injection increases tissue H 2 O 2 , thereby stimulating TRPA-1 on sensory nerve endings to produce inflammation and nociception. TRPV-1, by a previously unknown mechanism, also contributes to these responses.Gout is the most common cause of painful inflammatory arthritis among men and postmenopausal women. Mainly because of an aging population and lifestyle changes, the incidence and prevalence of gout are steadily increasing (1,2). Poorly controlled gout leads to a limitation of activities and a significant decrease in health-related quality of life (3). Signs and symptoms of gout are caused by soft tissue deposits of monosodium urate (MSU) crystals, which trigger episodes of intense articular and periarticular inflammation and excruciating pain (1,4). However, the underlying mechanism of the inflammatory process in gout that results in sensory symptoms and pain is poorly understood. Accordingly,
The treatment with the chemotherapeutic agent paclitaxel produces a painful peripheral neuropathy, and is associated with an acute pain syndrome in a clinically significant number of patients. However, no standard therapy has been established to manage the acute pain or the chronic neuropathic pain related to paclitaxel. In the present study, we evaluated the analgesic potential of two N-type voltage-gated calcium channel (VGCC) blockers, ω-conotoxin MVIIA and Phα1β, on acute and chronic pain induced by paclitaxel. Adult male rats were treated with four intraperitoneal injections of paclitaxel (1+1+1+1mg/kg, in alternate days) and the development of mechanical hyperalgesia was evaluated 24h (acute painful stage) or 15days (chronic painful stage) after the first paclitaxel injection. Not all animals showed mechanical hyperalgesia 24h after the first paclitaxel injection, but those that showed developed a more intense mechanical hyperalgesia at the chronic painful stage. Intrathecal administration (i.t.) of ω-conotoxin MVIIA (3-300pmol/site) or Phα1β (10-300pmol/site) reduced the mechanical hyperalgesia either at the acute or at the chronic painful stage induced by paclitaxel. When administered at the acute painful stage, ω-conotoxin MVIIA (300pmol/site, i.t.) and Phα1β (300pmol/site, i.t.) prevented the worsening of chronic mechanical hyperalgesia. Furthermore, Phα1β (30-300pmol/site, i.t.) elicited less adverse effects than ω-conotoxin MVIIA (10-300 pmol/site, i.t.). Taken together, our data evidence the involvement of N-type VGCC in pain sensitization induced by paclitaxel and point out the potential of Phα1β as a safer alternative than ω-conotoxin MVIIA to treat the pain related to paclitaxel.
Background: Methadone and ketamine are used in neuropathic pain management. However, the benefits of both drugs association are uncertain in the treatment of neuropathic pain. Objective: Our primary objective was test the hypothesis that oral methadone combined with oral ketamine is more effective than oral methadone or ketamine alone in reducing neuropathic pain. Study Design: We conducted a randomized, double blind, active-controlled parallelgroup clinical trial. Methods: Forty-two patients with neuropathic pain refractory to conventional therapy were randomly assigned to receive oral methadone (n = 14), ketamine (n = 14), or methadone plus ketamine (n = 14) over a 3-month period. Results: During these 90 days, we observed pain scores using a visual analogical scale (VAS), allodynia, burning/shooting pain, and some side effects. All treatments were effective in reducing pain scores by at least 40%. However, a significant improvement in pain was observed only in the ketamine alone group compared with both the methadone or methadone/ketamine groups. No significant differences were observed among the treatment groups for the reduction of burning or shooting pain, while ketamine alone was more effective than methadone or methadone/ketamine for the reduction of allodynia. Limitations: Formal assessment for awareness of the allocation was not performed, some co-intervention bias may have occurred, our results could be only relevant to the patient population investigated and the use of VAS as the primary outcome detect changes in pain intensity but not to assess neuropathic pain symptoms. Conclusion: This study indicates that ketamine was better than methadone or methadone/ketamine for treating neuropathic pain. Key words: Multimodal analgesia, refractory pain, NMDA receptor, opioid
Background Obesity is a multifactorial disease and a serious public health problem. Some of the associated factors are modifiable and, among them, the diet is highlighted. Objective To evaluate the association of dietary patterns of schoolchildren with obesity and body adiposity. Methods A cross-sectional study was carried out with 378 children aged 8 and 9 years, enrolled in urban schools in the city of Viçosa, Minas Gerais, Brazil. A semi-structured questionnaire was applied to the children and their caregivers on sociodemographic characteristics and life habits. Three 24-hour food recalls were used to identify dietary patterns; the Principal Component Analysis was employed. Weight and height were measured for the calculation of the body mass index (BMI) of the children and their mothers, waist circumference and neck circumference. Body composition was also evaluated through dual-energy X-ray absorptiometry (DXA). For all performed tests, the level of significance was set at 5%. Results Five dietary patterns (DP) were identified: “unhealthy”, “snacks”, “traditional”, “industrialized” and “healthy”. There was an association between excess weight (prevalence ratio [PR]: 1.38, 95% confidence interval [95%CI]: 1.02 to 1.87) and body fat (PR: 1.32, 95%CI : 1.07 to 1.64) with industrialized DP. There was an association between excess body fat (PR: 1.31, 95%CI: 1.01 to 1.74) and lower adherence to traditional DP. The other patterns were not associated with obesity and body adiposity. Conclusion Children with excess weight and body adiposity showed greater adherence to the industrialized DP and lower adherence to the traditional DP. We suggest that early assessments of dietary habits should be undertaken for monitoring and modifying these habits when necessary.
Resumo O objetivo deste artigo é avaliar o consumo de produtos ultraprocessados e fatores associados em crianças pré-púberes. Estudo transversal realizado com 378 crianças de 8 e 9 anos matriculadas em escolas públicas e privadas de Viçosa-MG. O consumo alimentar foi avaliado por três recordatórios de 24h. Os dados dietéticos foram tabulados no software Diet Pro® 5i, para quantificar o consumo energético. Para análise dos grupos de consumo alimentar foi utilizada a técnica Two-Step Cluster, por meio do software Stata versão 13.0. Os alimentos foram agrupados e classificados como marcadores de alimentação “saudável” e “não saudável”. A associação entre as variáveis sociodemográficas e os grupos formados foi verificada por meio da Regressão de Poisson. Obteve-se a formação de dois grupos alimentares: “saudável” e “não saudável”. A ingestão calórica de ultraprocessados foi menor no grupo “saudável” (20,5%) em relação ao “não saudável” (24,1%; P=0,043). No modelo multivariado, crianças de escola privada (RP = 1,25, P<0,001), que não recebiam Bolsa Família (RP=1,13, P=0,036) e cuja mãe trabalhava (RP=1,38, P<0,001) apresentaram maior chance de consumo “não saudável”. O consumo de produtos ultraprocessados associou-se ao maior poder aquisitivo das famílias de crianças pré-púberes.
To evaluate the effect of vitamin A supplementation in postpartum infants and women on serum retinol levels and breast milk. The databases Medline, PubMed, Lilacs and SciELO were consulted. The descriptors used were vitamin A, dietary supplement, child, postpartum period, infant and nutrition programs policies. Search found 7432 articles. After elimination of duplicity and application of eligibility criteria, 8 studies remained. All evaluated the effect of vitamin A supplementation on immediate postpartum, five studies used retinyl palmitate supplementation, one with retinyl palmitate and two did not specify the form of supplementation. Six studies evaluated colostrum and two included supplementation of children. It was found that supplementation in the puerperium increases the concentrations of serum retinol and breast milk, however, this result was in the short term and was relevant when the previous concentrations of the mother were low. When maternal serum concentrations are adequate, the retinol content in milk does not change, with little relevance for children. Further studies should be performed to evaluate the effect of megadoses supplementation on serum concentrations of children.
Polyamines (putrescine, spermidine and spermine) are aliphatic amines that are produced by the action of ornithine decarboxylase (ODC) in a rate-limiting and protein kinase C (PKC)-regulated step. Because high levels of polyamines are found in the synovial fluid of arthritic patients, the aim of the present study was to identify the role of peripherally produced polyamines in a model of inflammatory pain induced by adjuvant. The subcutaneous injection of Complete Freund's adjuvant (CFA, 50 μL/paw) caused the development of mechanical allodynia and edema. Moreover, it increased ODC expression and activity and PKC activation. Administration of the selective ODC inhibitor DFMO (10 μmol/paw) attenuated the development of allodynia and edema and decreased ODC activity in both control and CFA-treated animals. Furthermore, administration of the PKC inhibitor GF109203X (1 nmol/paw) reduced allodynia and ODC activity in animals injected with CFA. A subcutaneous injection of putrescine (10 μmol/paw), spermidine (3-10 μmol/paw) or spermine (0.3-3 μmol/paw) into the rat paw also caused mechanical allodynia and edema. The present results suggest that endogenously synthesized polyamines are involved in the development of nociception and edema caused by an adjuvant. Moreover, polyamine production in inflammatory sites seems to be related to an increase in ODC activity stimulated by PKC activation. Thus, controlling polyamine synthesis and action could be a method of controlling inflammatory pain.
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