Opioid‐modulating properties of the neuropeptide FF system

Abstract

Opioid receptors are involved in the control of pain perception in the central nervous system together with endogenous neuropeptides, termed opioid-modulating peptides, participating in a homeostatic system. Neuropeptide FF (NPFF) and related peptides possess anti-opioid properties, the cellular mechanisms of which are still unclear. The purpose of this review is to detail the phenomenon of cross-talk taking place between opioid and NPFF systems at the in vivo pharmacological level and to propose cellular and molecular models of functioning. A better knowledge of the mechanisms underlying opioid-modulating properties of NPFF has potential therapeutic interest for the control of opioid functions, notably for alleviating pain and/or for the treatment of opioid abuse.

GRK2 Protein-mediated Transphosphorylation Contributes to Loss of Function of μ-Opioid Receptors Induced by Neuropeptide FF (NPFF2) Receptors

“…Cross-or transphosphorylation between receptors offers an additional level of complexity to the regulation of GPCR activity and trafficking (56) that could be involved in the functional inhibition of MOP receptors by NPFF receptors. Indeed, activation of NPFF receptors negatively modulates MOP receptor pharmacological effects in vivo, as well as MOP receptor signaling in cellular and neuronal models (17). Because MOP and NPFF 2 receptors have been shown to heteromerize in recombinant SH-SY5Y cells (32), we have investigated here the phosphorylation status of MOP receptor in relation to the anti-opioid effect produced by NPFF 2 receptor activation in the SH-SY5Y model.…”

“…Injection of NPFF analogs in rodents has been shown to modulate both analgesic (12)(13)(14) and motivational properties of opioid drugs (15,16). The NPFF system is therefore considered to be an opioid-modulating system involved in homeostasis that counteracts the action of opioids (17,18) and thus an interesting therapeutic target for the management of opiate tolerance and dependence (7). In many cases, NPFF pretreatment inhibits opioid effects in rodents.…”

Opposite Effects of Neuropeptide FF on Central Antinociception Induced by Endomorphin-1 and Endomorphin-2 in Mice

“…NPFF system was demonstrated to mediate a variety of biological actions, such as food intake, body temperature, gastrointestinal modulation, cardiovascular and nociceptive action [11]–[13]. In addition, NPFF and opioid systems had been shown to interact at several levels, from receptor molecules to animal behavior [11], [14].…”

Development, Sex Steroid Regulation, and Phenotypic Characterization of RFamide-Related Peptide (Rfrp) Gene Expression and RFamide Receptors in the Mouse Hypothalamus

“…In rodents, RFRP-3-immunoreactivity (RFRP-3-ir) fibers project to several brain regions, including the paraventricular and arcuate nuclei, lateral hypothalamus, and the preoptic area, where some fibers appose GnRH neurons (6, 9 -11). Matching the presence of some RFRP-3-ir fibers in non-GnRH areas, RFPR-3 has also been shown to modulate nociception, body temperature, and food intake (12)(13)(14)(15)(16), suggesting that RFRP-3 may have additional biological functions outside reproduction.…”