ArticleThe journal of headache and pain2024
The crucial role of locus coeruleus noradrenergic neurons in the interaction between acute sleep disturbance and headache.
Article in The journal of headache and pain, 2024. 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, 6 citations in OpenAlex.
- Potential modulation of pain perception in animal models of acute sleep deprivation: implications of different stress response mechanisms.The journal of headache and pain · 2026Article
- A brainstem-thalamocortical circuit mediates postoperative pain duration induced by sleep deprivation.Behavioral and brain functions : BBF · 2026Article
- Noradrenergic Slow Vasomotion: The Hidden Fluid Pump Linking Sleep, Brain Clearance, and Dementia Pathogenesis.International journal of molecular sciences · 2025Review
- Mechanistic intersections between migraine and major depressive disorder.The journal of headache and pain · 2025Review
- At the Intersection of Pain and Sleep: a Roadmap for Preclinical Pain Research.Frontiers in pain research (Lausanne, Switzerland) · 2025Review
- Characteristics of locus coeruleus functional connectivity network in patients with comorbid migraine and insomnia.The journal of headache and pain · 2024Article
- The Locus Coeruleus in Chronic Pain.International journal of molecular sciences · 2024Review
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
backgroundBoth epidemiological and clinical studies have indicated that headache and sleep disturbances share a complex relationship. Although headache and sleep share common neurophysiological and anatomical foundations, the mechanism underlying their interaction remains poorly understood. The structures of the diencephalon and brainstem, particularly the locus coeruleus (LC), are the primary sites where the sleep and headache pathways intersect. To better understand the intricate nature of the relationship between headache and sleep, our study focused on investigating the role and function of noradrenergic neurons in the LC during acute headache and acute sleep disturbance.
methodTo explore the relationship between acute headache and acute sleep disturbance, we primarily employed nitroglycerin (NTG)-induced migraine-like headache and acute sleep deprivation (ASD) models. Initially, we conducted experiments to confirm that ASD enhances headache and that acute headache can lead to acute sleep disturbance. Subsequently, we examined the separate roles of the LC in sleep and headache. We observed the effects of drug-induced activation and inhibition and chemogenetic manipulation of LC noradrenergic neurons on ASD-induced headache facilitation and acute headache-related sleep disturbance. This approach enabled us to demonstrate the bidirectional function of LC noradrenergic neurons.
resultsOur findings indicate that ASD facilitated the development of NTG-induced migraine-like headache, while acute headache affected sleep quality. Furthermore, activating the LC reduced the headache threshold and increased sleep latency, whereas inhibiting the LC had the opposite effect. Additional investigations demonstrated that activating LC noradrenergic neurons further intensified pain facilitation from ASD, while inhibiting these neurons reduced this pain facilitation. Moreover, activating LC noradrenergic neurons exacerbated the impact of acute headache on sleep quality, while inhibiting them alleviated this influence.
conclusionThe LC serves as a significant anatomical and functional region in the interaction between acute sleep disturbance and acute headache. The involvement of LC noradrenergic neurons is pivotal in facilitating headache triggered by ASD and influencing the effects of headache on sleep quality.
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