Involvement of Mammalian RF-Amide Peptides and Their Receptors in the Modulation of Nociception in Rodents

Abstract

Mammalian RF-amide peptides, which all share a conserved carboxyl-terminal Arg–Phe–NH2 sequence, constitute a family of five groups of neuropeptides that are encoded by five different genes. They act through five G-protein-coupled receptors and each group of peptide binds to and activates mostly one receptor: RF-amide related peptide group binds to NPFFR1, neuropeptide FF group to NPFFR2, pyroglutamylated RF-amide peptide group to QRFPR, prolactin-releasing peptide group to prolactin-releasing peptide receptor, and kisspeptin group to Kiss1R. These peptides and their receptors have been involved in the modulation of several functions including reproduction, feeding, and cardiovascular regulation. Data from the literature now provide emerging evidence that all RF-amide peptides and their receptors are also involved in the modulation of nociception. This review will present the current knowledge on the involvement in rodents of the different mammalian RF-amide peptides and their receptors in the modulation of nociception in basal and chronic pain conditions as well as their modulatory effects on the analgesic effects of opiates.

The hypothalamic NPVF circuit modulates ventral raphe activity during nociception

“…In mammals, activation of the raphe nuclei are known to have an anti-nociceptive effect 15 16 , and some ventral raphe nuclei, including the ventrally located nucleus raphe magnus, project directly to the dorsal horn of the spinal cord to modulate pain 17 . Furthermore, systemic administration of RFamide receptor agonists has been reported to have a pro-nociceptive effect in rats 2 3 18 . As pain in humans is often treated by opioids, whose addictive properties have a profound negative societal impact 19 , the NPVF-serotonin circuit may be a novel target for development of alternative therapeutics for treatment of acute or chronic pain.…”

“…Among these are the RFamide peptides, RFRP-1/NPSV and RFRP-3/NPVF, cleaved from a preproprotein encoded by the npvf gene. PreproNPVF-derived peptides are produced by neurons in the hypothalamus, and have been analyzed using systemic pharmacology, revealing a role in nociception 2 3 . NPVF-derived peptides act through G-protein-coupled receptors and have anti-opioid effects, indicating the pro-nociceptive activity of these neuropeptides.…”

Genes encoding neuropeptide receptors are epigenetic markers in patients with head and neck cancer: a site-specific analysis

“…Members of the GPCR family include the neuropeptide FF (NPFF) receptors, of which there are two subtypes, NPFFR1 and NPFFR2, which bind the RF-amide related peptides and FF neuropeptides, respectively [ 11 ]. NPFFR1 and NPFFR2 are about 50% identical and are closely related to neuropeptide Y receptors and orexin receptors (30–35% homology) [ 12 ].…”

NPFFR2 Activates the HPA Axis and Induces Anxiogenic Effects in Rodents

“…There are five subtypes of mammalian RFamide peptides, including NPFF, RF-amide-related peptide (RFRP), pyroglutamylated RF-amide peptide (QRFP), prolactin releasing peptide (PrRP) and kisspeptin (KISS) [ 9 ]. Among these subtypes, NPFF-derived peptides include NPFF and NPAF, while Neuropeptide SF (NPSF, also known as RFRP-1) and Neuropeptide VF (NPVF, also known as RFRP-3) are NPVF-derived peptides [ 9 , 10 , 11 ]. Both NPFF- and NPVF-derived peptides show binding affinity with NPFF receptors.…”