Spotlight on Nociceptin/Orphanin FQ Receptor in the Treatment of Pain

Abstract

In our society today, pain has become a main source of strain on most individuals. It is crucial to develop novel treatments against pain while focusing on decreasing their adverse effects. Throughout the extent of development for new pain therapies, the nociceptin/orphanin FQ receptor (NOP receptor) has appeared to be an encouraging focal point. Concentrating on NOP receptor to treat chronic pain with limited range of unwanted effects serves as a suitable alternative to prototypical opioid morphine that could potentially lead to life-threatening effects caused by respiratory depression in overdose, as well as generate abuse and addiction. In addition to these harmful effects, the uprising opioid epidemic is responsible for becoming one of the most disastrous public health issues in the US. In this article, the contributing molecular and cellular structure in controlling the cellular trafficking of NOP receptor and studies that support the role of NOP receptor and its ligands in pain management are reviewed.

SLL-627 Is a Highly Selective and Potent κ Opioid Receptor (KOR) Agonist with an Unexpected Nonreduction in Locomotor Activity

“…Moreover, some orvinols, including etorphine, buprenorphine, thienorphine, the BU08028 and BU08070 series, the BU08073 series, BU10038 and the OREX-1019 series, as well as the phenyl substituted analogs of buprenorphine, exhibited low affinity and/or potency to the nociceptin/orphanin FQ opioid peptide (NOP) receptor, and functional regulation of NOP receptor was involved in analgesia, locomotor activity, abuse liability and reward, as well as other behavioral changes. ,− Whether the unique profile of SLL-627 was correlated to its potential action toward the NOP was not investigated in this work. Due to high variability and heterogeneity of data currently available, it is also difficult to predict the potential affinity of an orvinol analog toward the NOP receptor, but the affinity to the NOP receptor is always lower than that of the MOR, which is consistently observed for all of the above orvinols and structure-related analogs identified as either opioids with additional NOP affinity or bifunctional MOR/NOP modulators.…”

Up-and-coming Radiotracers for Imaging Pain Generators

“…59 NOP receptor ligands are being researched largely as an alternative to MOR opioid analgesics because NOP receptors are found in a variety of areas (including the brain, spinal dorsal horn, and dorsal root ganglion), which are important in transmitting pain. 60 The first results showed contradictory effects, both antinociceptive and nociceptive, but recently it was antinociceptive effects that were shown in nonhuman primates. 60 The calcitonin gene-related peptide, bradykinin, serotonin, brain-derived neurotrophic factor, N-methyl-D-aspartate, vanilloid receptor VR1, neurotensin, tyrosine kinase B, and cholecystokinin are other ligand-receptor systems that are typically increased in inflammatory pain and may be involved in modulating pain.…”

“…60 The first results showed contradictory effects, both antinociceptive and nociceptive, but recently it was antinociceptive effects that were shown in nonhuman primates. 60 The calcitonin gene-related peptide, bradykinin, serotonin, brain-derived neurotrophic factor, N-methyl-D-aspartate, vanilloid receptor VR1, neurotensin, tyrosine kinase B, and cholecystokinin are other ligand-receptor systems that are typically increased in inflammatory pain and may be involved in modulating pain. 61 These peptides could potentially be exploited for the purposes of imaging pain.…”

“… 59 NOP receptor ligands are being researched largely as an alternative to MOR opioid analgesics because NOP receptors are found in a variety of areas (including the brain, spinal dorsal horn, and dorsal root ganglion), which are important in transmitting pain. 60 The first results showed contradictory effects, both antinociceptive and nociceptive, but recently it was antinociceptive effects that were shown in nonhuman primates. 60 …”

Opioids and Their Receptors: Present and Emerging Concepts in Opioid Drug Discovery II

“…Since the discovery of the NOP receptor as the fourth member of the opioid receptor family, its role in different physiological and pathophysiological processes, especially pain, and the development of potential pain therapeutics was increasingly explored [ 28 ] This issue contains a review by El Daibani and Che, highlighting the analgesic utility of the nociception/orphanin FQ receptor (NOP) system [ 29 ]. The authors provide a detailed overview of almost two dozen NOP ligands and underscored the need for more high-resolution structures to be resolved beyond the current three crystal structures of the NOP receptor.…”