RESUMO
Bacterial infections are often accompanied by fever and generalized muscle pain. However, the treatment of pain with an infectious aetiology has been overlooked. Thus, we investigated the impact of cannabidiol (CBD) in bacterial lipopolysaccharide (LPS)-induced nociception. Male Swiss mice received intrathecal (i.t.) LPS injection, and the nociceptive threshold was measured by the von Frey filaments test. Spinal involvement of the cannabinoid CB2 receptor, toll-like receptor 4 (TLR4), microglia and astrocytes were evaluated by i.t. administration of their respectively antagonists or inhibitors. Western blot, immunofluorescence, ELISA and liquid chromatography-mass spectrometry were used to assess Cannabinoid CB2 receptors and TLR4 spinal expression, proinflammatory cytokines and endocannabinoid levels. CBD was administered intraperitoneally at 10 mg/kg. The pharmacological assay demonstrated TLR4 participation in LPS-induced nociception. In addition, spinal TLR4 expression and proinflammatory cytokine levels were increased in this process. CBD treatment prevented LPS-induced nociception and TLR4 expression. AM630 reversed antinociception and reduced CBD-induced endocannabinoids up-regulation. Increased spinal expression of the cannabinoid CB2 receptor was also found in animals receiving LPS, which was accompanied by reduced TLR4 expression in CBD-treated mice. Taken together, our findings indicated that CBD is a potential treatment strategy to control LPS-induced pain by attenuating TLR4 activation via the endocannabinoid system.
Assuntos
Canabidiol , Camundongos , Masculino , Animais , Canabidiol/farmacologia , Endocanabinoides/farmacologia , Lipopolissacarídeos/toxicidade , Nociceptividade , Receptor 4 Toll-Like/metabolismo , Dor , Receptor CB1 de CanabinoideRESUMO
OBJECTIVES: This study aimed to investigate the effect of cannabidiol (CBD) on type 4 Toll-like receptors (TLR4), glial cells and pro-inflammatory cytokines during the neuropathic pain induced by the chemotherapy agent paclitaxel (PTX), as well as the involvement of the endocannabinoid system in this process. METHODS: Male C57BL6 mice were subjected to PTX-induced neuropathic pain. To evaluate the involvement of the TLR4, glial cells and cannabinoid CB2 receptor, specific inhibitors or antagonists were intrathecally administered. The western blotting and immunofluorescence assay was performed to evaluate the spinal expression of TLR4, microglia, astrocytes and cannabinoid CB2 receptor. The levels of spinal pro-inflammatory cytokines and endocannabinoids were determined by enzyme-linked immunosorbent assay and liquid chromatography-mass spectrometry analysis, respectively. KEY FINDINGS: CBD prevented PTX-induced neuropathic pain, and the cannabinoid CB2 receptor antagonist AM630 reversed this effect. In addition, CBD treatment inhibited the spinal expression of TLR4 and Iba1 in mice with neuropathic pain. CBD also increased spinal levels of endocannabinoids anandamide and 2-arachidonoylglycerol, and reduced levels of cytokines in mice with neuropathic pain. CONCLUSIONS: CBD was efficient in preventing PTX-induced neuropathic pain, and this effect may involve inhibition of the TLR4 on microglia spinal with activation of the endocannabinoid system.
Assuntos
Antineoplásicos , Canabidiol , Canabinoides , Neuralgia , Masculino , Camundongos , Animais , Endocanabinoides/metabolismo , Canabidiol/farmacologia , Canabidiol/uso terapêutico , Receptor 4 Toll-Like , Receptor CB2 de Canabinoide/uso terapêutico , Camundongos Endogâmicos C57BL , Neuralgia/induzido quimicamente , Neuralgia/tratamento farmacológico , Neuralgia/prevenção & controle , Paclitaxel/uso terapêutico , Citocinas , Antineoplásicos/uso terapêuticoRESUMO
O presente estudo teve como objetivos: (1) produzir uma versão brasileira do Personality Adjective Check List (PACL), um instrumento para avaliação da personalidade baseado nos estilos saudáveis e patológicos de personalidade propostos por Millon, (2) verificar evidências de validade do instrumento por meio da análise fatorial dos itens (estrutura interna) e por meio da relação com variáveis externas, e (3) investigar a consistência interna do instrumento. Foram participantes 203 universitários, entre 18 e 50 anos de idade, sendo 98 homens e 105 mulheres. Foram encontrados cinco fatores que corroboraram pesquisas anteriores com o PACL. Os coeficientes de fidedignidade dos fatores originais variaram de 0,66 a 0,95. Os resultados sugerem que o PACL possui propriedades psicométricas adequadas.(AU)
This paper aimed: (1) to produce a Brazilian version of the Personality Adjective Check List (PACL), a test for personality assessment based on normal version styles proposed by Millon's personality disorders theory, (2) to verify validity evidence of the instrument by means of a factorial analysis (internal structure) and of the relationship with external variables, and (3) to investigate internal consistency of the scales. Participants were 203 undergraduate students, aged from 18 to 50 years old, 98 men and 105 women. It was found five factors in accordance with previous research on PACL. The reliability coefficients of the original factors ranged from 0,66 to 0,95. The results suggest that the PACL has adequate psychometric properties.(AU)
Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Determinação da Personalidade , Transtornos da Personalidade , Pesos e MedidasRESUMO
O presente estudo teve como objetivos: (1) produzir uma versão brasileira do Personality Adjective Check List (PACL), um instrumento para avaliação da personalidade baseado nos estilos saudáveis e patológicos de personalidade propostos por Millon, (2) verificar evidências de validade do instrumento por meio da análise fatorial dos itens (estrutura interna) e por meio da relação com variáveis externas, e (3) investigar a consistência interna do instrumento. Foram participantes 203 universitários, entre 18 e 50 anos de idade, sendo 98 homens e 105 mulheres. Foram encontrados cinco fatores que corroboraram pesquisas anteriores com o PACL. Os coeficientes de fidedignidade dos fatores originais variaram de 0,66 a 0,95. Os resultados sugerem que o PACL possui propriedades psicométricas adequadas.
This paper aimed: (1) to produce a Brazilian version of the Personality Adjective Check List (PACL), a test for personality assessment based on normal version styles proposed by Millon's personality disorders theory, (2) to verify validity evidence of the instrument by means of a factorial analysis (internal structure) and of the relationship with external variables, and (3) to investigate internal consistency of the scales. Participants were 203 undergraduate students, aged from 18 to 50 years old, 98 men and 105 women. It was found five factors in accordance with previous research on PACL. The reliability coefficients of the original factors ranged from 0,66 to 0,95. The results suggest that the PACL has adequate psychometric properties.