Neuropeptide FF receptors as therapeutic targets

Abstract

Neuropeptide FF (NPFF) receptors are G-protein-coupled receptors that belong to the subfamily of RF-amide receptors. Endogenous ligands for these receptors are peptides that display a conserved Arg-Phe-NH 2 (RF-amide) sequence at their carboxyl-terminal end. Several physiological functions have been proposed to be modulated by these receptors, mainly based on in vivo effects of their endogenous peptides or related molecules. These include the modulation of pain, feeding and cardiac function, and the control of insulin release. A wide body of evidence indicates a close relationship between NPFF and opioid systems. In particular, the NPFF system has been shown to display anti-opioid properties, which has led to the hypothesis that functional blockade of NPFF receptors could be a means to avoid the development of pain hypersensitivity and tolerance associated with chronic opioid treatment. This hypothesis was recently confirmed using a potent and selective antagonist of these receptors in a model of discontinuous opioid administration in rats. These results strongly suggest that NPFF receptors might represent a novel therapeutic target for improving the efficacy of opioid treatment of chronic pain.