ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2009
Substance P drives endocannabinoid-mediated disinhibition in a midbrain descending analgesic pathway.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 54 citations in OpenAlex.
- Targeting Spinal Dorsal Horn Sensitisation in Chronic Pain: Mechanisms and Translational Strategies.Neuroscience bulletin · 2026Review
- 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
- Substance P's Impact on Chronic Pain and Psychiatric Conditions-A Narrative Review.International journal of molecular sciences · 2024Review
- 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
- Changes in Dynamic Thiol/Disulfide Homeostasis, and Substance P, B-Endorphin and α-Tocopherol Concentrations in the Spinal Cord of Chronically Lame Dairy Cows.Animals : an open access journal from MDPI · 2023Article
- Article
- Cannabinoids and Opioids Differentially Target Extrinsic and Intrinsic GABAergic Inputs onto the Periaqueductal Grey Descending Pathway.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Positive Allosteric Modulators of Glycine Receptors and Their Potential Use in Pain Therapies.Pharmacological reviews · 2022Review
- TRPV1: A Common Denominator Mediating Antinociceptive and Antiemetic Effects of Cannabinoids.International journal of molecular sciences · 2022Review
- The Use of Zebrafish as a Non-traditional Model Organism in Translational Pain Research: The Knowns and the Unknowns.Current neuropharmacology · 2022Article
- Dual PI3Kδ/γ Inhibitor Duvelisib Prevents Development of Neuropathic Pain in Model of Paclitaxel-Induced Peripheral Neuropathy.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Cannabinoids Regulate Sensory Processing in Early Olfactory and Visual Neural Circuits.Frontiers in neural circuits · 2021Review
- Cannabinoids in the descending pain modulatory circuit: Role in inflammation.Pharmacology & therapeutics · 2020Review
- Opioid presynaptic disinhibition of the midbrain periaqueductal grey descending analgesic pathway.British journal of pharmacology · 2020Article
- Paracetamol is a centrally acting analgesic using mechanisms located in the periaqueductal grey.British journal of pharmacology · 2020Article
- Neuropeptide S-initiated sequential cascade mediated by OXJournal of biomedical science · 2020Article
- Inhibition of GABAergic Neurons and Excitation of Glutamatergic Neurons in the Ventrolateral Periaqueductal Gray Participate in Electroacupuncture Analgesia Mediated by Cannabinoid Receptor.Frontiers in neuroscience · 2019Article
- Substance P and pain chronicity.Cell and tissue research · 2019Review
- Cannabidiol Inhibits Endocannabinoid Signaling in Autaptic Hippocampal Neurons.Molecular pharmacology · 2018Article
- WWL70 protects against chronic constriction injury-induced neuropathic pain in mice by cannabinoid receptor-independent mechanisms.Journal of neuroinflammation · 2018Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Substance P is thought to play an essential role in several forms of supraspinally mediated analgesia. The actions of substance P on synaptic transmission within descending analgesic pathways, however, are largely unknown. Here, we used whole-cell recordings from rat midbrain slices to examine the effects of substance P on GABAergic and glutamatergic transmission within the periaqueductal gray (PAG), a key component of a descending analgesic pathway that projects via the rostral ventromedial medulla (RVM) to the spinal cord dorsal horn. We found that substance P reversibly decreased the amplitude and increased the paired-pulse ratio of evoked IPSCs recorded from identified PAG-RVM projection neurons and from unidentified PAG neurons. Substance P had no effect on miniature IPSCs, implying an indirect mode of action. The effects of substance P were abolished by metabotropic glutamate type 5 and cannabinoid CB1 receptor antagonists, but unaltered by NMDA, GABA(B), mu,delta-opioid, adenosine A(1), and 5HT(1A) receptor antagonists. Consistent with a role for endogenous glutamate in this process, substance P increased the frequency of action potential-dependent spontaneous EPSCs. Moreover, the effect of substance P on evoked IPSCs was mimicked and occluded by a glutamate transport inhibitor. Finally, these effects were dependent on postsynaptic G-protein activation and diacylglycerol lipase activity, suggesting the requirement for retrograde signaling by the endocannabinoid 2-arachidonoylglycerol. Thus, substance P may facilitate descending analgesia in part by enhancing glutamate-mediated excitation and endocannabinoid-mediated disinhibition of PAG-RVM projection neurons.
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Registered trials
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.