RESUMO
The N13 component of somatosensory evoked potential (N13 SEP) represents the segmental response of dorsal horn neurons. In this neurophysiological study, we aimed to verify whether N13 SEP might reflect excitability changes of dorsal horn neurons during central sensitization. In 22 healthy participants, we investigated how central sensitization induced by application of topical capsaicin to the ulnar nerve territory of the hand dorsum modulated N13 SEP elicited by ulnar nerve stimulation. Using a double-blind placebo-controlled crossover design, we also tested whether pregabalin, an analgesic drug with proven efficacy on the dorsal horn, influenced capsaicin-induced N13 SEP modulation. Topical application of capsaicin produced an area of secondary mechanical hyperalgesia, a sign of central sensitization, and increased the N13 SEP amplitude but not the peripheral N9 nor the cortical N20-P25 amplitude. This increase in N13 SEP amplitude paralleled the mechanical hyperalgesia and persisted for 120 min. Pregabalin prevented the N13 SEP modulation associated with capsaicin-induced central sensitization, whereas capsaicin application still increased N13 SEP amplitude in the placebo treatment session. Our neurophysiological study showed that capsaicin application specifically modulates N13 SEP and that this modulation is prevented by pregabalin, thus suggesting that N13 SEP may reflect changes in dorsal horn excitability and represent a useful biomarker of central sensitization in human studies.
Assuntos
Sensibilização do Sistema Nervoso Central , Potenciais Somatossensoriais Evocados , Adulto , Capsaicina/efeitos adversos , Sensibilização do Sistema Nervoso Central/efeitos dos fármacos , Método Duplo-Cego , Potenciais Somatossensoriais Evocados/efeitos dos fármacos , Feminino , Humanos , Hiperalgesia/induzido quimicamente , Hiperalgesia/fisiopatologia , Masculino , Fármacos do Sistema Sensorial/efeitos adversos , Adulto JovemRESUMO
Endocannabinoids are a group of biologically active endogenous lipids that have recently emerged as important mediators in energy balance control. The two best studied endocannabinoids, anandamide (N-arachidonoylethanolamine, AEA) and 2-arachidonoylglycerol (2-AG) are the endogenous ligands of the central and peripheral cannabinoid receptors. Furthermore, AEA binds to the transient receptor potential vanilloid type-1 (TRPV1), a capsaicin-sensitive, non-selective cation channel. The synthesis of these endocannabinoids is catalyzed by the N-acylphosphatidylethanolamine-selective phospholipase D (NAPE-PLD) and the sn-1-selective diacylglycerol lipase (DAGL), whereas their degradation is accomplished by the fatty acid amide hydrolase (FAAH) and the monoglyceride lipase (MGL), respectively. We investigated the presence of a functional endocannabinoid system in human adipose tissue from seven healthy subjects. Subcutaneous abdominal adipose tissue underwent biochemical and molecular biology analyses, aimed at testing the expression of this system and its functional activity. AEA and 2-AG levels were detected and quantified by HPLC. Real time PCR analyzed the expression of the endocannabinoid system and immunofluorescence assays showed the distribution of its components in the adipose tissue. Furthermore, binding assay for the cannabinoid and vanilloid receptors and activity assay for each metabolic enzyme of the endocannabinoid system gave clear evidence of a fully operating system. The data presented herein show for the first time that the human adipose tissue is able to bind AEA and 2-AG and that it is endowed with the biochemical machinery to metabolize endocannabinoids.
Assuntos
Tecido Adiposo/metabolismo , Ácidos Araquidônicos/metabolismo , Moduladores de Receptores de Canabinoides/metabolismo , Endocanabinoides , Glicerídeos/metabolismo , Alcamidas Poli-Insaturadas/metabolismo , Adolescente , Adulto , Sequência de Bases , Cromatografia Líquida de Alta Pressão , Feminino , Imunofluorescência , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , RNA/genética , RNA/metabolismo , Receptor CB1 de Canabinoide/genética , Receptor CB1 de Canabinoide/metabolismo , Receptor CB2 de Canabinoide/genética , Receptor CB2 de Canabinoide/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Canais de Cátion TRPV/genética , Canais de Cátion TRPV/metabolismoRESUMO
Cholelithiasis leads to 80,000 cholecystectomies being performed every year in France, but its prevalence is still unknown. The aim of this study was to assess the prevalence and risk factors of cholelithiasis in a random population of 1027 women and 727 men over the age of 30 in a small town in the southeast of France. Detailed clinical history, dietary investigation, and gallbladder ultrasound were collected for each subject and assessed by univariate analysis. A regression model was used in the multivariate analysis to detect the relative risk of cholelithiasis. Cholelithiasis was found in 130 individuals (global prevalence 13.9%). The relative risk for lithiasis was higher in women compared to men (1.89). Age (P<0.0001) and body mass index (BMI) >25 (P = 0.013) were also significant risk factors. Neither pregnancy nor oral contraceptive use proved to be risk factors. Typical biliary colic pain was the only symptom significantly associated with cholelithiasis (P<0.0001). These results show that the prevalence of gallstones in France is similar to that in Denmark and Italy.
