ArticleMolecular neurobiology2023
Impaired Ventrolateral Periaqueductal Gray-Ventral Tegmental area Pathway Contributes to Chronic Pain-Induced Depression-Like Behavior in Mice.
Article in Molecular neurobiology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 21 citations in OpenAlex.
- Distinct lateral hypothalamus GABAergic projections regulate sensory and affective dimensions of pain.Zoological research · 2026Article
- Peripheral Analgesic Effect of a Novel Curcuminoid Derivative: Possible Involvement of Peripheral Opioid Receptor and ATP-Sensitive Potassium Ion Channel.Pharmaceutics · 2026Article
- Baicalin Alleviates Chronic Restraint Stress-Induced Depression-like Behavior by Suppressing ROS/HAntioxidants (Basel, Switzerland) · 2026Article
- Recent progress in chronic pain-related negative emotions and cognitive dysfunction: insights into the mechanisms underlying neural circuitry.Frontiers in cellular neuroscience · 2026Review
- Synaptic plasticity in affective comorbidities of neuropathic pain: a bibliometric analysis based on WoSCC and PubMed (2003-2025).Frontiers in neurology · 2026Article
- Distinct and Shared Brain-Wide Activation Patterns in Mouse Models of Inflammatory and Neuropathic Pain.Journal of pain research · 2026Article
- Study on the Central Neural Pathways Connecting the Brain and Peripheral Acupoints Using Neural Tracers.CNS neuroscience & therapeutics · 2025Article
- Esketamine alleviates depressive-like behavior in neuropathic pain mice through the METTL3-GluA1 pathway.Cell biology and toxicology · 2025Article
- Pain mechanism and management strategy of rheumatoid arthritis.Frontiers in pain research (Lausanne, Switzerland) · 2025Review
- Factors Associated with Depression, Anxiety, and Sleep Disturbance Among Patients with Moderate-to-Severe Chronic Pain: A Multicenter Cross-Sectional Study.Journal of pain research · 2025Article
- The contribution of periaqueductal gray in the regulation of physiological and pathological behaviors.Frontiers in neuroscience · 2024Review
- Converging circuits between pain and depression: the ventral tegmental area as a therapeutic hub.Frontiers in pharmacology · 2023Review
- Puerarin improves the comorbidity of chronic pain and depression by binding with Bax and reducing mitochondrial dysfunction.Molecular painArticle
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chronic pain conditions within clinical populations are correlated with a high incidence of depression, and researchers have reported their high rate of comorbidity. Clinically, chronic pain worsens the prevalence of depression, and depression increases the risk of chronic pain. Individuals suffering from chronic pain and depression respond poorly to available medications, and the mechanisms underlying the comorbidity of chronic pain and depression remain unknown. We used spinal nerve ligation (SNL) in a mouse model to induce comorbid pain and depression. We combined behavioral tests, electrophysiological recordings, pharmacological manipulation, and chemogenetic approaches to investigate the neurocircuitry mechanisms of comorbid pain and depression. SNL elicited tactile hypersensitivity and depression-like behavior, accompanied by increased and decreased glutamatergic transmission in dorsal horn neurons and midbrain ventrolateral periaqueductal gray (vlPAG) neurons, respectively. Intrathecal injection of lidocaine, a sodium channel blocker, and gabapentin ameliorated SNL-induced tactile hypersensitivity and neuroplastic changes in the dorsal horn but not depression-like behavior and neuroplastic alterations in the vlPAG. Pharmacological lesion of vlPAG glutamatergic neurons induced tactile hypersensitivity and depression-like behavior. Chemogenetic activation of the vlPAG-rostral ventromedial medulla (RVM) pathway ameliorated SNL-induced tactile hypersensitivity but not SNL-elicited depression-like behavior. However, chemogenetic activation of the vlPAG-ventral tegmental area (VTA) pathway alleviated SNL-produced depression-like behavior but not SNL-induced tactile hypersensitivity. Our study demonstrated that the underlying mechanisms of comorbidity in which the vlPAG acts as a gating hub for transferring pain to depression. Tactile hypersensitivity could be attributed to dysfunction of the vlPAG-RVM pathway, while impairment of the vlPAG-VTA pathway contributed to depression-like behavior.
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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.