ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025
The Locus Coeruleus-Periaqueductal Gray GABAergic Projection Regulates Comorbid Pain and Depression.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Whole-Brain Monosynaptic Inputs to and Axonal Projections From Posterior Insular Cortex GABAergic Neurons in Mice.CNS neuroscience & therapeutics · 2026Article
- LCN2/SLC22A17 mediates the phagocytosis of GABAergic synapses by oligodendrocyte progenitor cells and contributes to cancer-induced pain and comorbid anxiety-like behaviors in mice.Acta neuropathologica communications · 2026Article
- A brainstem-thalamocortical circuit mediates postoperative pain duration induced by sleep deprivation.Behavioral and brain functions : BBF · 2026Article
- Prenatal Alcohol Exposure: Impact on Neuroimmune Function in the Stress Response and Pain.Advances in experimental medicine and biology · 2026Review
- Distinct nucleus accumbens neural pathways underlie separate behavioral features of chronic pain and comorbid depression.The Journal of clinical investigation · 2025Article
- The Locus Coeruleus-Periaqueductal Gray GABAergic Projection Regulates Comorbid Pain and Depression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Clinical characteristics and risk factors of depression in prodromal Parkinson's disease.Frontiers in neuroscience · 2025Article
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Authors and funding
8 authors.
Funding
Abstract
The locus coeruleus (LC) noradrenergic (NA) neurons regulate pain and depression through their projections to various downstream nuclei. Although GABAergic (GABA) neurons in and near the LC (LC-GABA neurons) provide inhibitory synaptic inputs to LC-NA neurons, it remains unknown whether they are implicated in neuropathic pain and comorbid depression through LC-NA neurons. This study demonstrates that LC-GABA neurons respond to noxious stimuli with enhanced activity, and stimulation of these neurons elevates pain thresholds and exerts an anti-depressant-like effect in naive and neuropathic pain mice. Conversely, inhibition of LC-GABA neurons leads to hyperalgesia and depression-like behaviors in naive mice and exacerbates existing pain- and depression-like behaviors in neuropathic pain mice. Although LC-GABA neurons inhibit pain responses in LC-NA neurons, they modulate pain thresholds and depression-like behaviors in a manner independent of LC-NA neurons. In contrast, the projection from LC-GABA neurons to the ventrolateral periaqueductal gray (vlPAG) is enhanced, and stimulation of this projection mimics that of LC-GABA neurons conferring analgesic- and antidepressant-like effects. This study reveals the enhancement of the LC
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