Analysis of the distribution of spinal NOP receptors in a chronic pain model using NOP‐eGFP knock‐in mice

Ozawa, Akihiko; Brunori, Gloria; Cippitelli, Andrea; Toll, Nicholas; Schoch, Jennifer J.; Kieffer, Brigitte L.; Toll, Lawrence

doi:10.1111/bph.14225

Cited by 19 publications

(15 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The exact mechanism behind this dichotomy remains unclear, but it is speculated that i.t. NOP receptor activation attenuates mechanical allodynia via hyperpolarization of (glycinergic) interneurons which are disinhibited upon injury, thereby enabling touch sensation to engage with nociceptive projection neurons (Ozawa et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

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

Sliepen

Korioth

Christoph

et al. 2020

British J Pharmacology

View full text Add to dashboard Cite

Background and Purpose: Cancer-induced bone pain remains inadequately controlled, and current standard of care analgesics is accompanied by several side effects. Nociceptin/orphanin FQ peptide (NOP) receptor agonists have demonstrated broad analgesic properties in rodent neuropathic and inflammatory pain models.Here, we investigate the analgesic potential of NOP receptor activation in a rodent cancer-induced bone pain model. Experimental Approach: Model validation by intratibial inoculation in male SpragueDawley rats was performed with varying MRMT-1/Luc2 cell quantities (0.5-1.5 × 10 6 Áml −1 ) and a behavioural battery (>14 days post-surgery) including evoked and non-evoked readouts: paw pressure test, cold plate, von Frey, open field, and weight distribution. Anti-allodynic potential of the endogenous NOP receptor ligand nociceptin (i.t.) and NOP receptor agonist Ro65-6570 ( i.p.) was tested using von Frey filaments, followed by a combination experiment with Ro65-6570 and the NOP receptor antagonist J-113397 (i.p.). Plasma cytokine levels and NOP receptor gene expression in dorsal root ganglion (DRG, L4-L6) and bone marrow were examined.

show abstract

Section: Discussionmentioning

confidence: 99%

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

Sliepen

Korioth

Christoph

et al. 2020

British J Pharmacology

View full text Add to dashboard Cite

show abstract

“…A von Frey plastic chamber was used to estimate mechanical allodynia as reported previously [ 17 ]. All animals were habituated to the test environment by placing them in the chamber for 2 h. An aesthesiometer was used to determine nociception by measuring the paw pressure threshold.…”

Section: Methodsmentioning

confidence: 99%

Ormosanine improves neuronal functions in spinal cord-injured rats by blocking peroxynitrite/calpain activity

Liu

et al. 2020

Translational Neuroscience

View full text Add to dashboard Cite

AbstractThe present study was performed to evaluate the effects of ormosanine against spinal cord injury (SCI) in rats and to examine the possible molecular mechanism of action. SCI was induced using an impactor device, and rats were treated with ormosanine 10, 50 or 100 mg/kg, p.o., for 10 days after induction of SCI. The effect of ormosanine on SCI was determined by estimating neurological functions and cytokines and parameters of oxidative stress level were estimated in SCI rats. Quantitative reverse transcription polymerase chain reaction, Western blotting analysis and histopathological study were performed on spinal tissue of SCI rats. The data suggested that treatment with ormosanine reversed the alterations of neurological function in SCI rats. Moreover, the levels of cytokines, oxidative stress and reactive oxygen species production were reduced in the ormosanine treatment group compared to the SCI group. The levels of calpain and neuronal nitric oxide synthase activity were significantly reduced in the spinal tissue of the ormosanine treatment group compared to the SCI group. Moreover, ormosanine treatment reduced the percentage of viable neurons in the spinal tissue of SCI rats. In conclusion, the results of this study showed that ormosanine treatment had a protective effect against neuronal injury in spinal cord-injured rats by regulating the peroxynitrite/calpain activity.

show abstract

“…Those four systems can interact with one another and are all deeply involved in the modulation of pain and reward. The NOP system, expressed mainly in the brainstem, forebrain and spinal cord (21)(22)(23), has a dual role in which its central stimulation blocks opioid-and stress-induced analgesia while intrathecal administration leads the analgesic properties (23)(24)(25). Because the NOP system activation decreases the reinforcing properties and abuse liability of many drugs of abuse, it is currently considered as a possible molecular target for substance abuse treatment (26)(27)(28).…”

Section: The Opioid System a Hub For Pain And Reward Interactionmentioning

confidence: 99%

Pain And Opioid Systems, Implications In The Opioid Epidemic

Massaly

Morón

2019

Current Opinion in Behavioral Sciences

View full text Add to dashboard Cite

Pain has a useful protective role; through avoidance learning, it helps to decrease the probability of engaging in tissue-damaging, or otherwise dangerous experiences. In our modern society, the experience of acute post-surgical pain and the development of chronic pain states represent an unnecessary negative outcome. This has become an important health issue as more than 30% of the US population reports experiencing "unnecessary" pain at any given time. Opioid therapies are often efficacious treatments for severe and acute pain; however, in addition to their powerful analgesic properties, opioids produce potent reinforcing properties and their inappropriate use has led to the current opioid overdose epidemic in North America. Dissecting the allostatic changes occurring in nociceptors and neuronal pathways in response to pain are the first and most important steps in understanding the physiologic changes underlying the opioid epidemic. Full characterization of these adaptations will provide novel targets for the development of safer pharmacotherapies. In this review, we highlight the current efforts toward safer opioid treatments and describe our current knowledge of the interaction between pain and opioid systems.

show abstract

Analysis of the distribution of spinal NOP receptors in a chronic pain model using NOP‐eGFP knock‐in mice

Abstract: Our findings suggest that the spinal NOP receptor system attenuates injury-induced hyperalgesia by direct inhibition of the projection neurons in the spinal cord that send nociceptive signals to the brain and not by inhibiting presynaptic terminals of DRG neurons in the superficial lamina.

Cited by 19 publications

References 57 publications

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

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

Ormosanine improves neuronal functions in spinal cord-injured rats by blocking peroxynitrite/calpain activity

Pain And Opioid Systems, Implications In The Opioid Epidemic

Contact Info

Product

Resources

About