NOP-Related Mechanisms in Pain and Analgesia

Toll, Lawrence; Ozawa, Akihiko; Cippitelli, Andrea

doi:10.1007/164_2019_214

Cited by 20 publications

(16 citation statements)

References 109 publications

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“…However, the N/OFQ system is very different from the classical opioid system in terms of biological functions, especially pain regulation [10][11][12]. Most studies have suggested that the N/ OFQ-NOP system can modulate pain in a bidirectional manner, which depends on several factors, such as the regulatory level in the nervous system (peripheral, spinal, or supraspinal) and the characteristics of pain (inflammatory pain, acute pain or neuropathic pain) [13][14][15][16][17]. However, to date, no consensus on the role of the N/OFQ-NOP system in pain control has been reached.…”

Section: Introductionmentioning

confidence: 99%

Behavioral Responses and Expression of Nociceptin/Orphanin FQ and Its Receptor (N/OFQ-NOP System) during Experimental Tooth Movement in Rats

Liao

Long

Zhang

et al. 2021

Pain Research and Management

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Objective. To determine behavioral testing after experimental tooth movement in rats and to explore the role of nociceptin/orphanin FQ and its receptor (the N/OFQ-NOP system) in pain induced by experimental tooth movement. Design. The mouth-wiping behavior of rats was assessed by studying behavioral responses after experimental tooth movement. The distribution of N/OFQ in the periodontal ligament, the trigeminal ganglion (TG), and the caudal one-third of the trigeminal subnucleus caudalis (Vc) was assessed by immunohistochemistry. The variations in N/OFQ expression in the TG and Vc were measured by Western blotting. The ongoing changes in the gene expression of the prepronociceptin gene and opioid receptor-like 1 receptor were assessed in the TG and Vc by real-time polymerase chain reaction (RT-PCR). Results. Overall, the mouth-wiping behavior increased significantly. The behavior first increased and then gradually decreased to a low level, showing cyclical variation. N/OFQ immunoreactivity increased in the periodontal ligament after tooth movement. ppN/OFQ mRNA and protein levels showed a time-dependent increase in the TG and were positively correlated with pain stimulus. NOP gene levels showed large fluctuations. In the Vc, the expression and changes in the N/OFQ-NOP system showed the opposite trend as those noted in TG and the periodontal membrane. Conclusion. The N/OFQ system may have a complex regulatory function in the pain induced by tooth movement and may be related to inflammation caused by orthodontic tooth movement and periodontal damage. The specific mechanism remains to be further studied.

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Section: Introductionmentioning

confidence: 99%

Behavioral Responses and Expression of Nociceptin/Orphanin FQ and Its Receptor (N/OFQ-NOP System) during Experimental Tooth Movement in Rats

Liao

Long

Zhang

et al. 2021

Pain Research and Management

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“…Ample evidence indicates that NOP receptors are widely distributed in the dorsal root ganglia (DRG), spinal dorsal horn (SDH), and brain areas that are involved in pain processing. Based on histological approaches and reporter fluorescent protein expression in rodents (Anton et al 1996;Chen and Sommer 2006;Florin et al 2000;Neal et al 1999a;Ozawa et al 2015), NOP receptors are expressed in both small-and large-diameter neurons of the DRG and trigeminal ganglia, found in both peptidergic and nonpeptidergic C-fibers, indicating that activation of the NOP receptor affects thermal and mechanical pain sensitivities (Ozawa et al 2018;Toll et al 2019). Consistently, abundant NOP receptor expression was also observed in the superficial area (laminae I and II) of the SDH that receive projections from sensory C-fibers.…”

Section: Expression Of N/ofq and Nop Receptor In Nervous Systemsmentioning

confidence: 86%

“…Like other classical opioid receptors, N/OFQ and NOP receptors were abundantly expressed in cortical regions (i.e., frontal cortex and cingulate cortex) and other multiple regions of the brain such as periaqueductal gray (PAG), locus coeruleus, and rostral ventromedial medulla (RVM), which directly impact ascending and descending pain pathways Schroder et al 2014;Toll et al 2019). Moreover, N/OFQ and NOP receptors were observed in the main mesolimbic pathway consisting of the central amygdala, the bed nucleus of the stria terminals, the ventral tegmental area (VTA), and nucleus accumbens (NAC), and also expressed in the hippocampus, thalamus, striatum, and other brain regions (Gehlert et al 2006;Letchworth et al 2000;Neal et al 1999b;Sim-Selley et al 2003;Sim and Childers 1997;Slowe et al 2001).…”

Section: Expression Of N/ofq and Nop Receptor In Nervous Systemsmentioning

confidence: 99%

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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“…Таким образом, действие N/OFQ на боль противоречиво, и полученные данные до сих пор не складываются в цельную картину. Тем не менее, доминирующим на сегодняшний день, является мнение, что одной из важнейших функций N/OFQ в центральных отделах системы проведения боли является противодействие эффектам опиоидов [56].…”

Section: роль N/ofq в регуляции болевой чувствительностиunclassified

The role of nociceptin in opioid regulation of brain functions

et al. 2021

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This review discusses our current knowledge on the nociceptin/orphanin (N/OFQ) system regarding its role in regulation of brain functions. Nociceptin receptor (NOPr) was identified in 1994 [Bunzow et al., 1994; Mollereau et al., 1994]. In 1995 a 17 amino acid endogenous peptide was found to be the high-affinity ligand for the NOPr [Reinscheid et al., 1995]. N/OFQ has a broad spectrum of activity and can act as on opioid-like as well as an anti-opioid peptide. Considering high level of N/OFQ and NOPr mRNA expression in the limbic brain regions, the N/OFQ/NOP system is suggested to be involved in regulation of emotions, resward, pain sensitivity, stress responsibility, sexual behavior, aggression, drug abuse and addiction. However it is still not well understood whether an increased vulnerability to drugs of abuse may be associated with dysregulation of N/OFQ/NOP system. Current review further highlights a need for further research on N/OFQ/NOP system as it could have clinical utility for substance abuse, depression, and anxiety pharmacotherapy.

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NOP-Related Mechanisms in Pain and Analgesia

Cited by 20 publications

References 109 publications

Behavioral Responses and Expression of Nociceptin/Orphanin FQ and Its Receptor (N/OFQ-NOP System) during Experimental Tooth Movement in Rats

Behavioral Responses and Expression of Nociceptin/Orphanin FQ and Its Receptor (N/OFQ-NOP System) during Experimental Tooth Movement in Rats

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

The role of nociceptin in opioid regulation of brain functions

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