ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2017
Compensatory Activation of Cannabinoid CB2 Receptor Inhibition of GABA Release in the Rostral Ventromedial Medulla in Inflammatory Pain.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 43 citations in OpenAlex.
- Endocannabinoid Modulation in Headache: Mechanisms, Models, and Translational Therapies.Cells · 2026Review
- Cannabinoid CBBritish journal of pharmacology · 2025Review
- Bone marrow-derived mesenchymal stem cells attenuate complete Freund's adjuvant-induced inflammatory pain by inhibiting the expression of P2X3.Cell proliferation · 2023Article
- Monoacylglycerol Lipase Protects the Presynaptic Cannabinoid 1 Receptor from Desensitization by Endocannabinoids after Persistent Inflammation.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Molecular identification of bulbospinal ON neurons by GPER, which drives pain and morphine tolerance.The Journal of clinical investigation · 2023Article
- Bulbospinal nociceptive ON and OFF cells related neural circuits and transmitters.Frontiers in pharmacology · 2023Review
- Peripheral sensory neuron CB2 cannabinoid receptors are necessary for both CB2-mediated antinociceptive efficacy and sparing of morphine tolerance in a mouse model of anti-retroviral toxic neuropathy.Pharmacological research · 2023Article
- Review
- Article
- Brain circuits for pain and its treatment.Science translational medicine · 2021Review
- Cannabinoid receptor 2 deletion influences social memory and synaptic architecture in the hippocampus.Scientific reports · 2021Article
- Cannabinoids in the descending pain modulatory circuit: Role in inflammation.Pharmacology & therapeutics · 2020Review
- Cannabinoid type 2 receptors inhibit GABAA receptor-mediated currents in cerebellar Purkinje cells of juvenile mice.PloS one · 2020Article
- Cannabinoid receptor 2‑selective agonist JWH015 attenuates bone cancer pain through the amelioration of impaired autophagy flux induced by inflammatory mediators in the spinal cord.Molecular medicine reports · 2019Article
- Electroacupuncture Stimulation Alleviates CFA-Induced Inflammatory Pain Via Suppressing P2X3 Expression.International journal of molecular sciences · 2019Article
- Novel analgesic effects of melanin-concentrating hormone on persistent neuropathic and inflammatory pain in mice.Scientific reports · 2018Article
- CB1 Agonism Alters Addiction-Related Behaviors in Mice Lacking Mu or Delta Opioid Receptors.Frontiers in psychiatry · 2018Article
- Pain Modulation: From Conditioned Pain Modulation to Placebo and Nocebo Effects in Experimental and Clinical Pain.International review of neurobiology · 2018Review
- The Endocannabinoid Reuptake Inhibitor WOBE437 Is Orally Bioavailable and Exerts Indirect Polypharmacological Effects via Different Endocannabinoid Receptors.Frontiers in molecular neuroscience · 2018Article
- Anxious behavior induces elevated hippocampal CbNeuroscience · 2017Article
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3 authors at 1 institution in 1 country.
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Abstract
The rostral ventromedial medulla (RVM) is a relay in the descending pain modulatory system and an important site of endocannabinoid modulation of pain. Endocannabinoids inhibit GABA release in the RVM, but it is not known whether this effect persists in chronic pain states. In the present studies, persistent inflammation induced by complete Freund's adjuvant (CFA) increased GABAergic miniature IPSCs (mIPSCs). Endocannabinoid activation of cannabinoid (CB1) receptors known to inhibit presynaptic GABA release was significantly reduced in the RVM of CFA-treated rats compared with naive rats. The reduction in CFA-treated rats correlated with decreased CB1 receptor protein expression and function in the RVM. Paradoxically, the nonselective CB1/CB2 receptor agonist WIN55212 inhibited GABAergic mIPSCs in both naive and CFA-treated rats. However, WIN55212 inhibition was reversed by the CB1 receptor antagonist rimonabant in naive rats but not in CFA-treated rats. WIN55212-mediated inhibition in CFA-treated rats was blocked by the CB2 receptor-selective antagonist SR144528, indicating that CB2 receptor function in the RVM is increased during persistent inflammation. Consistent with these results, CB2 receptor agonists AM1241 and GW405833 inhibited GABAergic mIPSC frequency only in CFA-treated rats, and the inhibition was reversed with SR144528. When administered alone, SR144528 and another CB2 receptor-selective antagonist AM630 increased mIPSC frequency in the RVM of CFA-treated rats, indicating that CB2 receptors are tonically activated by endocannabinoids. Our data provide evidence that CB2 receptor function emerges in the RVM in persistent inflammation and that selective CB2 receptor agonists may be useful for treatment of persistent inflammatory pain. SIGNIFICANCE STATEMENT: These studies demonstrate that endocannabinoid signaling to CB1 and CB2 receptors in adult rostral ventromedial medulla is altered in persistent inflammation. The emergence of CB2 receptor function in the rostral ventromedial medulla provides additional rationale for the development of CB2 receptor-selective agonists as useful therapeutics for chronic inflammatory pain.
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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.