ArticleThe Journal of clinical investigation2020
dmPFC-vlPAG projection neurons contribute to pain threshold maintenance and antianxiety behaviors.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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Who cites it
79 citing papers in PubMed, 126 citations in OpenAlex.
- Hierarchically and Temporally Distinct CaCNS neuroscience & therapeutics · 2026Article
- Glutamatergic Projection from the Ventrolateral Periaqueductal Gray to the Parafascicular Nucleus of the Thalamus Contributes to the Modulation of Neuropathic Pain in Mice.Neurochemical research · 2026Article
- VlPAG/DRN Microglia Drive Neuropathic Pain-Induced Depression via a Defined Neuroimmune Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Medium-intensity aerobic exercise can relieve mice anxiety by activating cannabinoid type 1 receptors on medial prefrontal cortex GABAergic neurons.Translational psychiatry · 2026Article
- Prelimbic cortex layer 5 GABAergic neurons mediate chronic pain and memory impairment by regulating excitatory/inhibitory imbalance.The journal of headache and pain · 2026Article
- A dual-pathway dysregulation in prefrontal-habenular circuits mediates stress susceptibility.Nature communications · 2026Article
- Distinct lateral hypothalamus GABAergic projections regulate sensory and affective dimensions of pain.Zoological research · 2026Article
- Article
- Microglial CR3-mediated synaptic pruning in the dmPFC promotes the generation and maintenance of chronic muscle pain via glutamatergic dysfunction.Experimental & molecular medicine · 2026Article
- Distinct and Shared Brain-Wide Activation Patterns in Mouse Models of Inflammatory and Neuropathic Pain.Journal of pain research · 2026Article
- CRH neurons in the AM-ACC circuit drive chronic pain and anxiety comorbidity.Frontiers in neuroscience · 2026Article
- LC-IL but Not LC-PL Circuit Regulates Comorbid Mechanical Hyperalgesia and Anxiety in Male Rats with Chronic Post-Surgical Pain.Journal of pain research · 2026Article
- Recent progress in chronic pain-related negative emotions and cognitive dysfunction: insights into the mechanisms underlying neural circuitry.Frontiers in cellular neuroscience · 2026Review
- Targeting the Medial Prefrontal Cortex with Transcranial Focused Ultrasound Alleviates Adolescent Sleep-Deprivation-Induced Persistent Postsurgical Pain in Adulthood.Research (Washington, D.C.) · 2026Article
- CDK5-Induced HCN2 Channel Dysfunction in the Prelimbic Cortex Drives Allodynia and Anxiety-Like Behaviors in Neuropathic Pain.Neuroscience bulletin · 2025Article
- Medial prefrontal cortex circuit dynamics involved in stage-specific addiction.Brain structure & function · 2025Review
- Chronic unpredictable stress produces hyperalgesia and promotes inhibitory drive in medial prefrontal cortex.The journal of pain · 2025Article
- Distinct nucleus accumbens neural pathways underlie separate behavioral features of chronic pain and comorbid depression.The Journal of clinical investigation · 2025Article
- Descending projection neurons in the primary sensorimotor cortex regulate neuropathic pain and locomotion in mice.Nature communications · 2025Article
- Accurate Chemogenetics Determines Electroacupuncture Analgesia Through Increased CB1 to Suppress the TRPV1 Pathway in a Mouse Model of Fibromyalgia.Life (Basel, Switzerland) · 2025Article
19 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
24 authors at 8 institutions in 2 countries.
Funding
Abstract
The dorsal medial prefrontal cortex (dmPFC) has been recognized as a key cortical area for nociceptive modulation. However, the underlying neural pathway and the function of specific cell types remain largely unclear. Here, we show that lesions in the dmPFC induced an algesic and anxious state. Using multiple tracing methods including a rabies-based transsynaptic tracing method, we outlined an excitatory descending neural pathway from the dmPFC to the ventrolateral periaqueductal gray (vlPAG). Specific activation of the dmPFC/vlPAG neural pathway by optogenetic manipulation produced analgesic and antianxiety effects in a mouse model of chronic pain. Inhibitory neurons in the dmPFC were specifically activated using a chemogenetic approach, which logically produced an algesic and anxious state under both normal and chronic pain conditions. Antagonists of the GABAA receptor (GABAAR) or mGluR1 were applied to the dmPFC, which produced analgesic and antianxiety effects. In summary, the results of our study suggest that the dmPFC/vlPAG neural pathway might participate in the maintenance of pain thresholds and antianxiety behaviors under normal conditions, while silencing or suppressing the dmPFC/vlPAG pathway might be involved in the initial stages and maintenance of chronic pain and the emergence of anxiety-like behaviors.
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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.