Mediators involved in the genesis of pain and the migration of leukocytes and in sepsis

Abstract

Our project consists of 3 subprojects which investigate a) mechanisms involved in the genesis of chronic and acute inflammatory pain as well as the mechanisms involved in the effects of different analgesics; b) mediators involved in the migration of neutrophils in different models of immune inflammation; c) mechanisms involved in the failure of the migration of neutrophils to the site of infection observed in serious sepsis. [...]. At molecular level we aim to determine the signaling paths and the transcription factors involved in sensibilization. Equally we will investigate molecular mechanisms involved in the analgesic actions of morphine and cannabinoids. As for mechanisms involved in the migration of leukocytes we intend to determine which cytokines, chemocines and their receptors are involved in the recruitment of leukocytes in different models of inflammatory diseases as well as the mechanisms by which these mediators induce migration. The modulating role of NO, CO, H2S, and PGJ2 on the migration will also be determined. It is intended also to determine the mechanisms by which salivas of vector insects modulate the inflammatory response. Finally, using in vivo and in vitro models we will determine the mechanisms involved in the failure of the migration of neutrophils in sepsis, focusing on the role of cytokines/chemocines, free radicals, Toll-like receptors, rolling/adhesion of neutrophils on the vascular endothelium, signaling paths and transcription factors and also the role of desensibilization of receptors for chemotaxic agents. (AU)