New and future drugs in nerve-gut dysfunction

There is increasing evidence that modifications in brain-gut communications are responsible for the occurrence of Functional Bowel Disorders. Based on various experimental models of modified gut sensitivity and the emergence of new pharmacological tools, it is now possible to identify new targets for the corrections of altered brain-gut communications and to improve our understanding of functional gastrointestinal disorders. Both local inflammatory related components and central nervous system acting factors are associated to trigger dysfunctioning and neuropeptides such as tachykinins, bradykinin and calcitonin gene-related peptide are involved in peripheral and spinal sensitization of afferent neurons. Serotonin released from entero chromaffin cells, mast cells, platelets or nerves also play a role, through different receptor subtypes, in initiating gut hypersensitivity. Brain modulation of impaired ascending messages also appears to be an important approach for the correction of symptoms related to gut hyper-responsiveness.