A re-evaluation of the neurochemical and anatomical bases of chemotherapy-induced vomiting
Nissar A. Darmani
Department of Basic Medical Sciences, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766-1854, USA
Abstract:
Chemotherapy-induced nausea and vomiting (CINV) is a complex pathophysiological condition and consists of two phases. The goal of this presentation is to bridge the existing gaps in the literature and more critically evaluate the anatomical and neurotransmitter bases of central/peripheral components of CINV. The conventional CINV neurotransmitter hypothesis suggests that the immediate phase is mainly due to release of serotonin from the enterochromaffin cells in the GIT, while the delayed phase is a consequence of release of substance P (SP) activating NK1 receptors in the brainstem. However, recent findings argue against this simplistic view. Our revision of the hypothesis advocates a more complex, differential and overlapping involvement of several emetic neurotransmitter (e.g. dopamine, serotonin, substance P, prostaglandins, leukotrienes and related arachidonic acid derived metabolites) in both phases of emesis occurring concomitantly in the brainstem and in the GIT enteric nervous system. No single antiemetic is currently available to completely prevent either phases of CINV. The standard antiemetic regimens include a 5-HT3 antagonist plus dexamethasone for the prevention of acute emetic phase, combined with an NK1 antagonist for the delayed phase. Although NK1 antagonists behave in animals as broad-spectrum antiemetics, by themselves they are not very effective against CINV in patients. Cannabinoids activate CB1 receptors and also behave as broad-spectrum antiemetics against against both phases of CINV. Potential side effects may limit the clinical utility of direct-acting cannabinoid agonists which could be avoided by the use of corresponding indirect-acting agonists.
