ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2015
Therapeutic potential of inhibitors of endocannabinoid degradation for the treatment of stress-related hyperalgesia in an animal model of chronic pain.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 1 of them a synthesis that pooled it.
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Who cites it
61 citing papers in PubMed, 1 synthesis or guideline pooled it, 137 citations in OpenAlex.
- The antidepressant and anxiolytic effects of cannabinoids in chronic unpredictable stress: a preclinical systematic review and meta-analysis.Translational psychiatry · 2022Pooled it
- Cannabinoids and Extracellular Vesicles as Potential Biomarkers and Therapeutic Targets in Neuropsychiatric Disorders: A Hypothesis-Driven Review.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Circuit mechanisms governing endocannabinoid modulation of affective behaviour and stress adaptation.Nature reviews. Neuroscience · 2025Review
- Visceral Pain in Preterm Infants with Necrotizing Enterocolitis: Underlying Mechanisms and Implications for Treatment.Paediatric drugs · 2025Review
- Endocannabinoid Hydrolase Inhibitors: Potential Novel Anxiolytic Drugs.Drug design, development and therapy · 2024Review
- A monoacylglycerol lipase inhibitor showing therapeutic efficacy in mice without central side effects or dependence.Nature communications · 2023Article
- Extraction and Simultaneous Quantification of Endocannabinoids and Endocannabinoid-Like Lipids in Biological Tissues.Methods in molecular biology (Clifton, N.J.) · 2023Article
- 2-Arachidonoylglycerol-mediated endocannabinoid signaling modulates mechanical hypersensitivity associated with alcohol withdrawal in mice.Alcoholism, clinical and experimental research · 2022Article
- Persistent muscle hyperalgesia after adolescent stress is exacerbated by a mild-nociceptive input in adulthood and is associated with microglia activation.Scientific reports · 2022Article
- Stress-induced changes in nociceptive responding post-surgery in preclinical rodent models.Frontiers in pain research (Lausanne, Switzerland) · 2022Review
- mGluR5-Mediated eCB Signaling in the Nucleus Accumbens Controls Vulnerability to Depressive-Like Behaviors and Pain After Chronic Social Defeat Stress.Molecular neurobiology · 2021Article
- Targeting Monoacylglycerol Lipase in Pursuit of Therapies for Neurological and Neurodegenerative Diseases.Molecules (Basel, Switzerland) · 2021Review
- Sphingolipid and Endocannabinoid Profiles in Adult Attention Deficit Hyperactivity Disorder.Biomedicines · 2021Article
- Therapeutic Attributes of Endocannabinoid System against Neuro-Inflammatory Autoimmune Disorders.Molecules (Basel, Switzerland) · 2021Review
- Selective inhibition of monoacylglycerol lipase is associated with passive coping behavior and attenuation of stress-induced dopamine release in the medial prefrontal cortex.Neurobiology of stress · 2021Article
- From an Alternative Medicine to a New Treatment for Refractory Epilepsies: Can Cannabidiol Follow the Same Path to Treat Neuropsychiatric Disorders?Frontiers in psychiatry · 2021Review
- Article
- Meet Your Stress Management Professionals: The Endocannabinoids.Trends in molecular medicine · 2020Review
- Activation of tyrosine phosphatase PTP1B in pyramidal neurons impairs endocannabinoid signaling by tyrosine receptor kinase trkB and causes schizophrenia-like behaviors in mice.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2020Article
- Protective effects of elevated anandamide on stress and fear-related behaviors: translational evidence from humans and mice.Molecular psychiatry · 2020Article
1 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The occurrence of chronic stress, depression, and anxiety can increase nociception in humans and may facilitate the transition from localized to chronic widespread pain. The mechanisms underlying chronic widespread pain are still unknown, hindering the development of effective pharmacological therapies. Here, we exposed C57BL/6J mice to chronic unpredictable stress (CUS) to investigate how persistent stress affects nociception. Next, mice were treated with multiple intramuscular nerve growth factor (NGF) injections, which induced chronic widespread nociception. Thus, combination of CUS and NGF served as a model where psychophysiological impairment coexists with long-lasting hyperalgesia. We found that CUS increased anxiety- and depression-like behavior and enhanced basal nociception in mice. When co-applied with repeated NGF injections, CUS elicited a sustained long-lasting widespread hyperalgesia. In order to evaluate a potential therapeutic strategy for the treatment of chronic pain associated with stress, we hypothesized that the endocannabinoid system (ECS) may represent a target signaling system. We found that URB597, an inhibitor of the anandamide-degrading enzyme fatty acid amide hydrolase (FAAH), and JZL184, an inhibitor of the 2-arachidonoyl glycerol-degrading enzyme monoacylglycerol lipase (MAGL), increased eCB levels in the brain and periphery and were both effective in reducing CUS-induced anxiety measured by the light-dark test and CUS-induced thermal hyperalgesia. Remarkably, the long-lasting widespread hyperalgesia induced by combining CUS and NGF was effectively reduced by URB597, but not by JZL184. Simultaneous inhibition of FAAH and MAGL did not improve the overall therapeutic response. Therefore, our findings indicate that enhancement of anandamide signaling with URB597 is a promising pharmacological approach for the alleviation of chronic widespread nociception in stress-exposed mice, and thus, it could represent a potential treatment strategy for chronic pain associated with neuropsychiatric disorders in humans.
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