ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2021
The role of medial prefrontal cortex projections to locus ceruleus in mediating the sex differences in behavior in mice with inflammatory pain.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 30 citations in OpenAlex.
- The Intraplantar CFA Inflammatory Pain Model Incompletely Captures Pain Comorbidities Across Sexes.Journal of neuroscience research · 2026Article
- Doxazosin Alleviates Chronic Orofacial Pain.International journal of molecular sciences · 2026Article
- A Glutamatergic Medial Prefrontal Cortex-Locus Coeruleus Circuit Drives Intestinal Dysmotility in Diarrhea-Predominant Irritable Bowel Syndrome.International journal of molecular sciences · 2026Article
- Obesity suppresses hippocampal neurogenesis and impairs memory and executive function in a weight and sex-specific manner.Physiology & behavior · 2026Article
- Neural Circuit Connections and Functions of Locus Coeruleus-Norepinephrine System.International journal of molecular sciences · 2025Review
- Bidirectional emotional regulation through prefrontal innervation of the locus coeruleus.Molecular psychiatry · 2025Article
- A systematic review of the pain-related emotional and cognitive impairments in chronic inflammatory pain induced by CFA injection and its mechanism.IBRO neuroscience reports · 2025Review
- Green Light Exposure Reduces Primary Hyperalgesia and Proinflammatory Cytokines in a Rodent Model of Knee Osteoarthritis: Shedding Light on Sex Differences.Biomedicines · 2024Article
- Large-scale coupling of prefrontal activity patterns as a mechanism for cognitive control in health and disease: evidence from rodent models.Frontiers in neural circuits · 2024Review
- Norepinephrine depletion in the brain sex-dependently modulates aspects of spatial learning and memory in female and male rats.Psychopharmacology · 2023Article
- Sex-specific biobehavioral regulation of persistent inflammatory pain by alcohol.Alcohol, clinical & experimental research · 2023Article
- Anti-inflammatory effects of β-FNA are sex-dependent in a pre-clinical model of LPS-induced inflammation.Journal of inflammation (London, England) · 2023Article
- Characterization of pain-, anxiety-, and cognition-related behaviors in the complete Freund's adjuvant model of chronic inflammatory pain in Wistar-Kyoto rats.Frontiers in pain research (Lausanne, Switzerland) · 2023Article
- Skin-resident dendritic cells mediate postoperative pain via CCR4 on sensory neurons.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
We tested the hypothesis that the cognitive impairment associated with inflammatory pain may result from dysregulation of the top-down control of locus ceruleus's (LC) activity by the medial prefrontal cortex (mPFC). Injection of complete Freund's adjuvant (CFA) served as a model for inflammatory pain. The CFA injection decreased the thermal thresholds in both sexes but only the male mice showed increased anxiety-like behavior and diminished cognition, while the females were not affected. Increased calcium fluorescence, a marker for neuronal activity, was detected by photometry in the mPFC of males but not in females with CFA. Next, while chemogenetic inhibition of the projections from the mPFC to the LC improved the object recognition memory of males with pain, the inhibition of the mPFC to LC pathway in female mice produced anxiolysis and spatial memory deficits. The behavior results prompted us to compare the reciprocal innervation of mPFC and LC between the sexes. We used an anterograde transsynaptic tagging technique, which relies on postsynaptic cre transfer, to assess the innervation of LC by mPFC efferents. The males showed a higher rate of postsynaptic cre transfer into LC neurons from mPFC efferents than the females. And vice versa, a retrograde tracing experiment demonstrated that LC to mPFC projection neurons were more numerous in females when compared to males. In conclusion, we provide evidence that subtle differences in the reciprocal neuronal circuit between the LC and mPFC may contribute to sex differences associated with the adverse cognitive effects of inflammatory pain.
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