The nociceptin/orphanin FQ receptor system as a target to alleviate cancer‐induced bone pain in rats: Model validation and pharmacological evaluation

Sliepen, Sonny Hermanus Johannes; Korioth, Johanna; Christoph, Thomas; Tzschentke, Thomas; Diaz‐delCastillo, Marta; Heegaard, Anne‐Marie; Rutten, Kris

doi:10.1111/bph.14899

Cited by 7 publications

(7 citation statements)

References 62 publications

(104 reference statements)

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“…Intrathecal administration of N/OFQ or NOPR agonists reduce pain sensitivity in animal models of neuropathic and inflammatory pain (Hao et al, 1998;Ko and Naughton, 2009;Tzschentke et al, 2017). Similar effects are observed with systemic NOPR agonists on mechanical allodynia in preclinical models of cancer-induced bone pain (Sliepen et al, 2021).…”

Section: Nociceptin/orphanin Fq Opioid Receptormentioning

confidence: 68%

Endogenous opioid systems alterations in pain and opioid use disorder

Higginbotham

Markovic

Massaly

et al. 2022

Front. Syst. Neurosci.

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Decades of research advances have established a central role for endogenous opioid systems in regulating reward processing, mood, motivation, learning and memory, gastrointestinal function, and pain relief. Endogenous opioid systems are present ubiquitously throughout the central and peripheral nervous system. They are composed of four families, namely the μ (MOPR), κ (KOPR), δ (DOPR), and nociceptin/orphanin FQ (NOPR) opioid receptors systems. These receptors signal through the action of their endogenous opioid peptides β-endorphins, dynorphins, enkephalins, and nociceptins, respectfully, to maintain homeostasis under normal physiological states. Due to their prominent role in pain regulation, exogenous opioids—primarily targeting the MOPR, have been historically used in medicine as analgesics, but their ability to produce euphoric effects also present high risks for abuse. The ability of pain and opioid use to perturb endogenous opioid system function, particularly within the central nervous system, may increase the likelihood of developing opioid use disorder (OUD). Today, the opioid crisis represents a major social, economic, and public health concern. In this review, we summarize the current state of the literature on the function, expression, pharmacology, and regulation of endogenous opioid systems in pain. Additionally, we discuss the adaptations in the endogenous opioid systems upon use of exogenous opioids which contribute to the development of OUD. Finally, we describe the intricate relationship between pain, endogenous opioid systems, and the proclivity for opioid misuse, as well as potential advances in generating safer and more efficient pain therapies.

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Section: Nociceptin/orphanin Fq Opioid Receptormentioning

confidence: 68%

Endogenous opioid systems alterations in pain and opioid use disorder

Higginbotham

Markovic

Massaly

et al. 2022

Front. Syst. Neurosci.

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“…of nociceptin (amino acid chain 1-17). The nociceptin dose administered in this study is similar to those used in previous experiments [37].…”

Section: Experimental Groupsmentioning

confidence: 91%

Nociceptin Increases Antioxidant Expression in the Kidney, Liver and Brain of Diabetic Rats

Adeghate

D’Souza

Saeed

et al. 2021

Biology

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Nociceptin (NC) consists of 17 amino acids (aa) and takes part in the processing of learning and memory. The role of NC in the induction of endogenous antioxidants in still unclear. We examined the effect of NC on the expression of endogenous antioxidants in kidney, liver, cerebral cortex (CC), and hippocampus after the onset of diabetes mellitus, using enzyme-linked immunosorbent assay and immunohistochemistry. Exogenous NC (aa chain 1–17; 10 µg/kg body weight) was given intraperitoneally to normal and diabetic rats for 5 days. Our results showed that catalase (CAT) is present in the proximal (PCT) and distal (DCT) convoluted tubules of kidney, hepatocytes, and neurons of CC and hippocampus. The expression of CAT was significantly (p < 0.05) reduced in the kidney of normal and diabetic rats after treatment with NC. However, NC markedly (p < 0.001) increased the expression CAT in the liver and neurons of CC of diabetic rats. Superoxide dismutase (SOD) is widely distributed in the PCT and DCT of kidney, hepatocytes, and neurons of CC and hippocampus. NC significantly (p < 0.001) increased the expression of SOD in hepatocytes and neurons of CC and the hippocampus but not in the kidney. Glutathione reductase (GRED) was observed in kidney tubules, hepatocytes and neurons of the brain. NC markedly increased (p < 0.001) the expression of GRED in PCT and DCT cells of the kidney and hepatocytes of liver and neurons of CC. In conclusion, NC is a strong inducer of CAT, SOD, and GRED expression in the kidney, liver and brain of diabetic rats.

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“…Thomas Tzschentke (2021) describes the evidence for anti-nociceptive and analgesic effects of bisphosphonates, with a detailed discussion of potential mechanisms of action. Aligned with this, Sliepen et al (2021) investigate nociceptin/orphanin FQ receptor agonists, demonstrating the potential for this system for the treatment of cancer-induced bone pain. Bisphosphonates have been in use for decades for the treatment of osteoporosis and cancer-induced bone disease and, as is evident throughout this editorial, are one of the most widely studied classes of drugs in musculoskeletal research.…”

Section: Linked Articlesmentioning

confidence: 99%