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Accueil > UMR 7242 Biotechnologie et signalisation cellulaire (Jean-Luc Galzi) > Récepteurs, protéines membranaires et innovation thérapeutique (Animation scientifique : Isabelle Schalk) > RCPG, douleur et inflammation (Frédéric Simonin) > Nos thématiques > RF-amide receptors in OIH & CPIH

RF-amide receptors in OIH & CPIH

Role of mammalian RF-amide receptors in hyperalgesia induced by opiates (OIH) and chronic pain (CPIH)

Sustained stimulation of opioid receptors turns on anti-opioid systems that counterbalance the analgesic effects of opiates. This lowers the threshold of pain sensation (hyperalgesia) and reduces efficacy of pain treatments (tolerance). We have recently shown that neuropeptide FF (NPFF) receptors are involved in hyperalgesia and tolerance to opiates (Simonin et al. 2006 ; Elhabazi et al. 2012).
NPFF receptors belong to a subfamily of GPCRs called RF-amide receptors that includes NPFF1 and NPFF2 receptor subtypes, GPR10, GPR54 and GPR103. Endogenous ligands for these receptors display a conserved Arg-Phe-NH2 (RF-amide) sequence at their carboxyl-terminus that is critical for their activity (Simonin 2006).

Some pieces of evidence suggest that, in addition to NPFF receptors, other members of this family could also play an important role in the modulation of nociception and OIH (Laurent et al. 2005 ; Yamamoto et al. 2008).

However, the implication of each individual RF-amide receptors in these phenomena has not yet been clearly addressed. In addition, the mechanism by which opiates activate NPFF receptors and other anti-opioid systems and how these systems counteract the antinociceptive effect of opioids is still largely unknown. Finally, the participation of these systems to the development of pain hypersensitivity in chronic pain syndromes has never been investigated so far. In most cases, pharmacological and genetic tools for the study of RF-amide receptors are missing.

Our main goal will be to generate such tools in order to address these questions.


RF9 blocks opioid-induced hyperalgesia and analgesic tolerance
Stimulation of opioid receptors triggers activation of anti-opioid systems that in turn produce hyperalgesia and thus diminish the net analgesic effect of the opioid agonist. When chronically co-injected with an opiate, RF9 completely blocks the delayed and long lasting paradoxical opioid induced-hyperalgesia and prevents the development of associated tolerance.


References :

Elhabazzi et al , 2012, British J. Pharmacol. 165, 424-435

Laurent et al, 2005, Nat Neurosci 8, 1735-1741

Yamamoto et al, 2008, Neuroscience 157, 214-222

Simonin et al, 2006, Proc. Natl. Acad. Sci. USA 103, 466-471

Simonin, 2006, Drugs of the Future 31, 603-609


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