Electrophysiological Actions of N/OFQ

Winters, Bryony L.; Christie, MacDonald J.; Vaughan, Christopher W.

doi:10.1007/164_2019_205

Cited by 12 publications

(9 citation statements)

References 211 publications

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“…These actions of NOP receptor agonists are consistent with electrophysiological studies showing that NOP receptor activation can inhibit voltage-gated calcium channels (Cav) in small-and medium-diameter DRG neurons via Gi/o protein-dependent pathways (Abdulla and Smith 1998;Winters et al 2019). N/OFQ preferentially inhibits N-type current to a greater degree than other Cav-mediated current in the DRG neurons (Beedle et al 2004;Winters et al 2019). It is worth noting that N/OFQ prevented capsaicin-elicited calcium increases in human DRG neurons (Anand et al 2016), suggesting that activation of peripheral NOP receptors may produce antinociceptive effects.…”

Section: Effects Of Selective Nop Agonists In the Primary Sensory Neuronssupporting

confidence: 83%

“…administration in diabetic rats (Schiene et al 2015). These actions of NOP receptor agonists are consistent with electrophysiological studies showing that NOP receptor activation can inhibit voltage-gated calcium channels (Cav) in small-and medium-diameter DRG neurons via Gi/o protein-dependent pathways (Abdulla and Smith 1998;Winters et al 2019). N/OFQ preferentially inhibits N-type current to a greater degree than other Cav-mediated current in the DRG neurons (Beedle et al 2004;Winters et al 2019).…”

Section: Effects Of Selective Nop Agonists In the Primary Sensory Neuronssupporting

confidence: 67%

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Therapeutic potentials of NOP and MOP receptor coactivation for the treatment of pain and opioid abuse

Kiguchi

Ding

2020

J of Neuroscience Research

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Following the identification of the nociceptin/orphanin FQ (N/OFQ) peptide (NOP) as an endogenous ligand for the NOP receptor, ample evidence has revealed unique functional profiles of the N/OFQ-NOP receptor system. NOP receptors are expressed in key neural substrates involved in pain and reward modulation. In non-human primates (NHPs), NOP receptor activation effectively exerts antinociception and anti-hypersensitivity at the spinal and supraspinal levels. Moreover, NOP receptor activation inhibits dopaminergic transmission and synergistically enhances mu-opioid peptide (MOP) receptor-mediated analgesia. In this article, we discuss the functional profiles of ligands with dual NOP and MOP receptor agonist activities and highlight their optimal functional efficacy for pain relief and drug abuse treatment. Through coactivation of NOP and MOP receptors, bifunctional NOP/MOP receptor "partial" agonists (e.g., AT-121, BU08028, and BU10038) reveal a wider therapeutic window with fewer side effects. These newly developed ligands potently induce antinociception without MOP receptor agonist-associated side effects such as abuse potential, respiratory depression, itch sensation, and physical dependence. In addition, in both rodent and NHP models, bifunctional NOP/MOP receptor agonists can attenuate reward processing and/or the reinforcing effects of opioids and other abused drugs. While a mixed NOP/opioid receptor "full" agonist cebranopadol is undergoing clinical trials, bifunctional NOP/MOP "partial" agonists exhibit promising therapeutic profiles in translational NHP models for the treatment of pain and opioid abuse. This class of drugs demonstrates the therapeutic advantage of NOP and MOP receptor coactivation, indicating a greater potential for future development.

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Section: Effects Of Selective Nop Agonists In the Primary Sensory Neuronssupporting

confidence: 83%

Section: Effects Of Selective Nop Agonists In the Primary Sensory Neuronssupporting

confidence: 67%

Therapeutic potentials of NOP and MOP receptor coactivation for the treatment of pain and opioid abuse

Kiguchi

Ding

2020

J of Neuroscience Research

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“…Furthermore, the Gβγ subunit regulates several intracellular signaling kinase cascades, including protein kinase C (PKC), phospholipase A (PLA) and C (PLC), and extracellular signal-regulated kinases 1 and 2 (ERK1/2) [ 57 ]. The positive modulation of the postsynaptic Kir3 channel’s function generates neuronal hyperpolarization and firing inhibition, while the blocked of presynaptic Cav2.x calcium channels reduces neurotransmitter release (for an extensive review on the electrophysiological actions of N/OFQ see [ 58 ]). Despite sharing the same cellular mechanism of action of classical opioid receptors, NOP differs in its anatomical distribution, which makes its functional role unique.…”

Section: Neurobiology Of the N/ofq-nop Receptor Systemmentioning

confidence: 99%

Role of Nociceptin/Orphanin FQ-NOP Receptor System in the Regulation of Stress-Related Disorders

Ubaldi

Cannella

Borruto

et al. 2021

IJMS

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Nociceptin/orphanin FQ (N/OFQ) is a 17-residue neuropeptide that binds the nociceptin opioid-like receptor (NOP). N/OFQ exhibits nucleotidic and aminoacidics sequence homology with the precursors of other opioid neuropeptides but it does not activate either MOP, KOP or DOP receptors. Furthermore, opioid neuropeptides do not activate the NOP receptor. Generally, activation of N/OFQ system exerts anti-opioids effects, for instance toward opioid-induced reward and analgesia. The NOP receptor is widely expressed throughout the brain, whereas N/OFQ localization is confined to brain nuclei that are involved in stress response such as amygdala, BNST and hypothalamus. Decades of studies have delineated the biological role of this system demonstrating its involvement in significant physiological processes such as pain, learning and memory, anxiety, depression, feeding, drug and alcohol dependence. This review discusses the role of this peptidergic system in the modulation of stress and stress-associated psychiatric disorders in particular drug addiction, mood, anxiety and food-related associated-disorders. Emerging preclinical evidence suggests that both NOP agonists and antagonists may represent a effective therapeutic approaches for substances use disorder. Moreover, the current literature suggests that NOP antagonists can be useful to treat depression and feeding-related diseases, such as obesity and binge eating behavior, whereas the activation of NOP receptor by agonists could be a promising tool for anxiety.

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“…As a newly-discovered neuropeptide, Orphanin FQ (OFQ) is in the family of endogenous opioid peptide but has different physiological functions (Winters et al, 2019). OFQ immunoreactivity could be observed in the ventrolateral PAG (vlPAG), NRM, dorsal raphe nucleus (DRN; Ma et al, 2004).…”

Section: Other Transmitters Related To Ea-induced Analgesiamentioning

confidence: 99%

The Involvement of Descending Pain Inhibitory System in Electroacupuncture-Induced Analgesia

Gan

et al. 2019

Front. Integr. Neurosci.

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Chronic pain is a major health problem, which can impair quality of life and reduce productivity. Electroacupuncture (EA), a modality of medicine based on the theories of Traditional Chinese Medicine (TCM), presents great therapeutic effects on chronic pain. Its clinical application has gained increasing popularity, and in parallel, more research has been performed on the mechanisms of EA-induced analgesia. The past decades have seen enormous advances both in neuronal circuitry of needle-insertion and in its molecular mechanism. EA may block pain by activating the descending pain inhibitory system, which originates in the brainstem and terminates at the spinal cord. This review article synthesizes corresponding studies to elucidate how EA alleviate pain via the mediation of this descending system. Much emphasis has been put on the implication of descending serotonergic and noradrenergic pathways in the process of pain modulation. Also, other important transmitters and supraspinal regions related to analgesic effects of EA have been demonstrated. Finally, it should be noticed that there exist some shortcomings involved in the animal experimental designed for EA, which account for conflicting results obtained by different studies.

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Electrophysiological Actions of N/OFQ

Cited by 12 publications

References 211 publications

Therapeutic potentials of NOP and MOP receptor coactivation for the treatment of pain and opioid abuse

Therapeutic potentials of NOP and MOP receptor coactivation for the treatment of pain and opioid abuse

Role of Nociceptin/Orphanin FQ-NOP Receptor System in the Regulation of Stress-Related Disorders

The Involvement of Descending Pain Inhibitory System in Electroacupuncture-Induced Analgesia

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