ArticleNeuropharmacology2016
Stress induces analgesia via orexin 1 receptor-initiated endocannabinoid/CB1 signaling in the mouse periaqueductal gray.
Article in Neuropharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.
- Cannabinoid Receptors, Mental Pain and Suicidal Behavior: a Systematic Review.Current psychiatry reports · 2018Pooled it
- Acute and chronic stress differentially regulate pain via distinct ensembles in the paraventricular nucleus of hypothalamus.Molecular psychiatry · 2026Article
- Orexinergic projections to substantia innominata mediate arousal and analgesia.British journal of anaesthesia · 2025Article
- Corticosterone stimulates synthesis of 2-arachidonoylglycerol via putative membrane-bound glucocorticoid receptors and inhibits GABA release via CB1 cannabinoid receptors in the ventrolateral periaqueductal gray.Molecular pharmacology · 2025Article
- Hypocretin: a promising target for the regulation of homeostasis.Frontiers in neuroscience · 2025Review
- Effects of Stress Exposure to Pain Perception in Pre-Clinical Studies: Focus on the Nociceptin/Orphanin FQ-NOP Receptor System.Brain sciences · 2024Review
- Orexinergic neurons modulate stress coping responses in mice.Frontiers in molecular neuroscience · 2023Article
- Hypothalamic orexinergic neurons modulate pain and itch in an opposite way: pain relief and itch exacerbation.The journal of physiological sciences : JPS · 2022Article
- Electroacupuncture reduces chronic itchFrontiers in pharmacology · 2022Article
- Median Nerve Stimulation as a Nonpharmacological Approach to Bypass Analgesic Tolerance to Morphine: A Proof-of-Concept Study in Mice.The journal of pain · 2021Article
- Research progress on the mechanism of orexin in pain regulation in different brain regions.Open life sciences · 2021Review
- Medial prefrontal cortex diclofenac-induced antinociception is mediated through GPR55, cannabinoid CB1, and mu-opioid receptors of this area and periaqueductal gray.Naunyn-Schmiedeberg's archives of pharmacology · 2020Article
- Neuropeptide S-initiated sequential cascade mediated by OXJournal of biomedical science · 2020Article
- The Lateral Hypothalamus: An Uncharted Territory for Processing Peripheral Neurogenic Inflammation.Frontiers in neuroscience · 2020Review
- Involvement of brain-derived neurotrophic factor (BDNF) in chronic intermittent stress-induced enhanced mechanical allodynia in a rat model of burn pain.BMC neuroscience · 2019Article
- Median nerve stimulation induces analgesia via orexin-initiated endocannabinoid disinhibition in the periaqueductal gray.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Orexins and stress.Frontiers in neuroendocrinology · 2018Review
- The peripheral corticotropin-releasing factor (CRF)-induced analgesic effect on somatic pain sensitivity in conscious rats: involving CRF, opioid and glucocorticoid receptors.Inflammopharmacology · 2018Review
- Periaqueductal Gray Glutamatergic Transmission Governs Chronic Stress-Induced Depression.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2018Article
- Electroacupuncture Potentiates Cannabinoid Receptor-Mediated Descending Inhibitory Control in a Mouse Model of Knee Osteoarthritis.Frontiers in molecular neuroscience · 2018Article
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
The orexin system consists of orexin A/hypocretin 1 and orexin B/hypocretin 2, and OX1 and OX2 receptors. Our previous electrophysiological study showed that orexin A in the rat ventrolateral periaqueductal gray (vlPAG) induced antinociception via an OX1 receptor-initiated and endocannabinoid-mediated disinhibition mechanism. Here, we further characterized antinociceptive effects of orexins in the mouse vlPAG and investigated whether this mechanism in the vlPAG can contribute to stress-induced analgesia (SIA) in mice. Intra-vlPAG (i.pag.) microinjection of orexin A in the mouse vlPAG increased the hot-plate latency. This effect was mimicked by i.pag. injection of WIN 55,212-2, a CB1 agonist, and antagonized by i.pag. injection of the antagonist of OX1 (SB 334867) or CB1 (AM 251), but not OX2 (TCS-OX2-29) or opioid (naloxone), receptors. [Ala(11), D-Leu(15)]-orexin B (i.pag.), an OX2 selective agonist, also induced antinociception in a manner blocked by i.pag. injection of TCS-OX2-29, but not SB 334867 or AM 251. Mice receiving restraint stress for 30 min showed significantly longer hot-plate latency, more c-Fos-expressing orexin neurons in the lateral hypothalamus and higher orexin levels in the vlPAG than unrestrained mice. Restraint SIA in mice was prevented by i.pag. or intraperitoneal injection of SB 334867 or AM 251, but not TCS-OX2-29 or naloxone. These results suggest that during stress, hypothalamic orexin neurons are activated, releasing orexins into the vlPAG to induce analgesia, possibly via the OX1 receptor-initiated, endocannabinoid-mediated disinhibition mechanism previously reported. Although activating either OX1 or OX2 receptors in the vlPAG can lead to antinociception, only OX1 receptor-initiated antinociception is endocannabinoid-dependent.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.