Antinociceptive effect of Mansoa alliacea polar extracts involves opioid receptors and nitric oxide in experimental nociception in mice.

To evaluate the antinociceptive effect and the possible mechanism of action of two polar extracts of Mansoa alliacea, a medicinal plant used in Perú, Brazil, and Mexico to treat rheumatic pain, we used the formalin and hot-plate tests in mice. We found that ethanolic (MA-EtOH) and aqueous (MA-AQ) extracts of M. alliacea induced antinociceptive effects in both nociceptive tests. The antinociceptive efficacy of the highest dosage (300 mg/kg) of both extracts were also compared by using intraperitoneal and oral administration in the formalin test. Results showed that intraperitoneal injection of the two extracts produced better antinociceptive effects than that obtained by their oral administration. The mechanism of action involved in their antinociceptive activity was determined in the formalin test. Results showed that the presence of A784168 (TRPV1 antagonist) did not alter the antinociceptive effect induced by any of the M. alliacea extracts, whereas naltrexone (opioid antagonist) partially prevented the antinociceptive effect only of MA-EtOH in both phases of the formalin test. Furthermore, the effects of the extracts were diminished by L-NAME (inhibitor of nitric oxide synthase), but not by ODQ (inhibitor of the soluble guanylyl cyclase) or glibenclamide (blocker of K+ATP channels) in the neurogenic phase. However, the effect of MA-AQ was diminished by all the inhibitors in the inflammatory phase. These results support the use of M. alliacea as a potential natural product with efficacy for pain relief depending on the form of preparation and the route of administration by involving opioid receptors and the production of nitric oxide.

Endophenotypes and biomarkers: an approach to molecular genetic studies of mental disorders / Endofenotipos y biomarcadores: un enfoque hacia el estudio genético molecular de los trastornos mentales

Many precise aspects of the etiology and pathophysiology of mental disorders are still unknown. Susceptibility to these disorders depends in part on variability in the genome sequence among individuals. The genotype, a given environment, a specific epigenetic profile and stochastic factors affect the phenotype, which includes body structures, physiological processes, and behavior. Since the access to the Central Nervous System is generally difficult and in most cases there are still no biological tests that necessarily contribute to diagnosis, psychiatric phenotypes are usually limited to clinical symptoms and functioning. Therefore, researchers are currently seeking alternatives to facilitate the identification of genetic risk factors. One strategy is to identify measurable biological, cognitive, and behavioral markers, intermediate phenotypes, or endophenotypes, which in the best case may be simpler than general psychiatric diagnoses, ideally with a precise biological meaning and a more direct relationship with the action of specific genes. Endophenotypes have been very useful in other fields of medicine. Currently, there are several proposed criteria and specifications for endophenotypes. Examples of possible types of endophenotypes or biomarkers, as well as treatment response phenotypes in some psychiatric disorders will be discussed in this review.

Aún se desconocen diversos aspectos de la etiología y fisiopatología de los trastornos mentales. La susceptibilidad a éstos depende en parte de la variabilidad en la secuencia genómica en las personas. El genotipo, un ambiente dado, un perfil epigenético específico y factores estocásticos afectan el fenotipo, el cual incluye estructuras corporales, procesos fisiológicos y conducta. Los fenotipos psiquiátricos generalmente se limitan al funcionamiento y a los síntomas clínicos, debido a que el acceso al Sistema Nervioso Central es complicado y en la mayoría de los casos no hay pruebas biológicas que necesariamente contribuyan al diagnóstico. Por esta razón, en la actualidad se buscan alternativas para facilitar la identificación de factores de riesgo de tipo genético. La identificación de marcadores biológicos, cognitivos o conductuales medibles, fenotipos intermedios o endofenotipos podría ser una de estas nuevas opciones. Estos marcadores podrían ser más simples que el diagnóstico psiquiátrico general, y de manera ideal tendrían un significado biológico preciso y una acción más directa en los genes. El empleo de endofenotipos ha sido útil en otras ramas de la medicina. Hasta ahora se han propuesto diversos criterios y especificaciones para los endofenotipos. En esta revisión se describirán posibles tipos de endofenotipos o biomarcadores, así como fenotipos relacionados con la respuesta farmacológica en algunos trastornos psiquiátricos.