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The ORL-1 Receptor System: Are There Opportunities for Antagonists in Pain Therapy?

[ Vol. 8 , Issue. 16 ]


Beatriz Fioravanti and Todd W. Vanderah   Pages 1442 - 1451 ( 10 )


Following the cloning of the classical opioid receptors (μ, δ and κ), the opioid receptor like-1 (ORL-1) was identified as a G-protein coupled receptor (GPCR) with 65% structure homology to the other members of the opioid family. Its endogenous ligand nociception/orphanin FQ (N/OFQ) was discovered shortly thereafter, becoming the subject of investigation in numerous studies. Since activation of the ORL-1 receptor by N/OFQ leads to Gαi-coupling and signal transduction similar to that of opioid receptors, N/OFQ was thought to have a role in pain modulation, similar to that of the endogenous opioids. Surprisingly, studies characterizing N/OFQs effects on pain transmission yielded conflicting results, attributing to N/OFQ both pronociceptive and antinociceptive actions, depending on doses and routes of administration as well as species and sex of the subjects. With the development of selective and potent ORL-1 antagonists, many scientists believed these contradicting actions would be elucidated. Here we review the recent literature reporting the use of novel ORL-1 antagonists, both peptide and non-peptide, in different models of pain and discuss their use as research tools or potential drug candidates.


Antagonists, cloning, opioid receptor, G-protein coupled receptor (GPCR), peptide, ligand, Inflammatory Pain


Department of Pharmacology and Anesthesiology, College of Medicine at the University of Arizona, 1501 N. Campbell Ave, LSN 567, Tucson, AZ 85724 USA.

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