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

Safia Ayachi,Frã©Dã©Ric Simonin

doi:10.3389/fendo.2014.00158

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.

Highlights

A tetrapeptide Phe–Met–Arg–Phe–NH2 (FMRF-NH2) has been isolated in 1977 by Price and Greenberg and was described as having cardioexcitatory properties in the neverid clam Macrocallista nimbosa [1]
In mice with chronic inflammatory pain induced by complete Freund’s adjuvant, the decrease of morphine rewarding properties were associated with an increase of NPFFR2 agonist [125I]-EYWSLAAPQRFNH2 binding in several brain regions involved in morphine reward including the shell of the nucleus accumbens, the major islands of Calleja and the ventral endopiriform nucleus
As in vitro binding experiments have shown that prolactin-releasing peptide (PrRP) display high affinity for NPFFR1 and NPFFR2 [6, 107, 120], it is tempting to speculate that these receptors could represent endogenous targets of PrRP in some brain areas. In agreement with this hypothesis, we have shown that in rats the increase in blood pressure and heart rate induced by i.c.v. administration of PrRP is blocked by the NPFFR1/R2 selective antagonist RF9, while they are still present in Otsuka Long-Evans Tokushima Fatty (OLETF) rat strain, in which the GRP10 receptor gene was mutated [125]

Summary

INTRODUCTION

A tetrapeptide Phe–Met–Arg–Phe–NH2 (FMRF-NH2) has been isolated in 1977 by Price and Greenberg and was described as having cardioexcitatory properties in the neverid clam Macrocallista nimbosa [1]. In mice with chronic inflammatory pain induced by complete Freund’s adjuvant, the decrease of morphine rewarding properties were associated with an increase of NPFFR2 agonist [125I]-EYWSLAAPQRFNH2 binding in several brain regions involved in morphine reward including the shell of the nucleus accumbens, the major islands of Calleja and the ventral endopiriform nucleus These data indicate that NPFF and NPFFR2 are probably upregulated in different models of inflammatory pain in rodents and that NPFF displays antiallodynic and anti-hyperalgesic effects in these models. I.c.v. injection of RFRP-1, when given alone, had no effect on hot plate latencies in the rat but when co-administrated with morphine, it decreased or blocked morphine analgesia in hot plate and formalin tests [10] These data suggest that, like NPFF, RFRP-1 action depends on opioid receptors activation, supporting its role in an anti-opioid system related to the opioid system. These data attest that kisspeptin regulates pain and/or nociceptive sensitization in mice, and may be predominantly implicated during inflammatory pain

CONCLUSION

Findings

Results