ArticleeNeuro
The Role of Glutamatergic and Dopaminergic Neurons in the Periaqueductal Gray/Dorsal Raphe: Separating Analgesia and Anxiety.
Article in eNeuro. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 94 citations in OpenAlex.
- VlPAG/DRN Microglia Drive Neuropathic Pain-Induced Depression via a Defined Neuroimmune Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Article
- Cannabinoid CB1 receptor and mu-opioid receptor interaction: new insights from conditional knockout mice.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Dopaminergic neurons in the dorsal raphe nucleus may modulate social dominance in mice.Zoological research · 2025Article
- Role of astrocytic mu-opioid receptors of the ventrolateral periaqueductal gray in modulating anxiety-like responses.Behavioral and brain functions : BBF · 2025Article
- Chronic inflammatory pain and chronic THC vapor inhalation alter midbrain neuronal activity.Journal of neurophysiology · 2025Article
- Article
- Role of the Dorsal Raphe Nucleus in Pain Processing.Brain sciences · 2024Review
- Gamma-aminobutyric acid and glutamate/glutamine levels in the dentate nucleus and periaqueductal gray in new daily persistent headache: a magnetic resonance spectroscopy study.The journal of headache and pain · 2024Article
- Multiple Posterior Insula Projections to the Brainstem Descending Pain Modulatory System.International journal of molecular sciences · 2024Article
- Article
- Modulating Neural Circuits of Pain in Preclinical Models: Recent Insights for Future Therapeutics.Cells · 2024Review
- Dopamine Pharmacodynamics: New Insights.International journal of molecular sciences · 2024Review
- Control of defensive behavior by the nucleus of Darkschewitsch GABAergic neurons.National science review · 2024Article
- Low-Frequency Stimulation of Trpv1-Lineage Peripheral Afferents Potentiates the Excitability of Spino-Periaqueductal Gray Projection Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Role of 5-hydroxytryptamine type 3 receptors in the regulation of anxiety reactions.Journal of Zhejiang University. Science. B · 2024Article
- The contribution of periaqueductal gray in the regulation of physiological and pathological behaviors.Frontiers in neuroscience · 2024Review
- Article
- Brainstem Modulation of Nociception by Periaqueductal Gray Neurons Expressing the μ-Opioid Receptor in Mice.Anesthesiology · 2023Article
- Divergent modulation of pain and anxiety by GABAergic neurons in the ventrolateral periaqueductal gray and dorsal raphe.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
Abstract
The periaqueductal gray (PAG) is a significant modulator of both analgesic and fear behaviors in both humans and rodents, but the underlying circuitry responsible for these two phenotypes is incompletely understood. Importantly, it is not known if there is a way to produce analgesia without anxiety by targeting the PAG, as modulation of glutamate or GABA neurons in this area initiates both antinociceptive and anxiogenic behavior. While dopamine (DA) neurons in the ventrolateral PAG (vlPAG)/dorsal raphe display a supraspinal antinociceptive effect, their influence on anxiety and fear are unknown. Using DAT-cre and Vglut2-cre male mice, we introduced designer receptors exclusively activated by designer drugs (DREADD) to DA and glutamate neurons within the vlPAG using viral-mediated delivery and found that levels of analgesia were significant and quantitatively similar when DA and glutamate neurons were selectively stimulated. Activation of glutamatergic neurons, however, reliably produced higher indices of anxiety, with increased freezing time and more time spent in the safety of a dark enclosure. In contrast, animals in which PAG/dorsal raphe DA neurons were stimulated failed to show fear behaviors. DA-mediated antinociception was inhibitable by haloperidol and was sufficient to prevent persistent inflammatory pain induced by carrageenan. In summary, only activation of DA neurons in the PAG/dorsal raphe produced profound analgesia without signs of anxiety, indicating that PAG/dorsal raphe DA neurons are an important target involved in analgesia that may lead to new treatments for 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.