ArticleAnnals of neurology2021
Optogenetic Spreading Depression Elicits Trigeminal Pain and Anxiety Behavior.
Article in Annals of neurology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.
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Who cites it
52 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Mechanosensitive receptors in migraine: a systematic review.The journal of headache and pain · 2024Pooled it
- Behavioral Deficits and Cortical Network Dysfunction Following Repeated Mild Traumatic Brain Injuries.Journal of neurotrauma · 2026Article
- PN6047 Demonstrates Broad Preclinical Efficacy in Headache Models as a Novel Delta-Opioid Receptor Agonist.bioRxiv : the preprint server for biology · 2026Article
- Intranasal hybrid nanoparticles encapsulating rizatriptan enhance antimigraine efficacy in an optogenetic spreading depression model.International journal of pharmaceutics · 2026Article
- Tsunamis hiding in plain sight: spreading depression in clinical neurology.Nature reviews. Neurology · 2026Review
- Sex-dependent cognitive and behavioral outcomes induced by repetitive cortical spreading depression in mice.The journal of headache and pain · 2026Article
- Meningeal neuropeptide and neuroimmune interactions in the context of migraine.The journal of headache and pain · 2026Review
- Spreading depolarization activates the cGAS-STING pathway and drives cranial nociception: therapeutic potential of STING modulation.The journal of headache and pain · 2026Article
- Is canonical SD a clinically relevant model of migraine? Argument pro.The journal of headache and pain · 2025Review
- Article
- Mechanisms underlying the increased susceptibility to initiation of cortical spreading depression in a genetic mouse model of migraine.The journal of headache and pain · 2025Article
- Spreading depolarization as a therapeutic target in migraine.Nature reviews. Neurology · 2025Review
- Brain-Wide Spatiotemporally Distinct Traveling Waves Drive Anxiety-Like Behaviors in Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Oral atogepant mitigates spreading depolarization-induced pain and anxiety behavior in mice.The journal of headache and pain · 2025Article
- Susceptibility Weighted Imaging in Migraines with and Without Aura: A Case-Control Study.Neurology international · 2025Article
- The mysterious link between migraine aura and migraine headache.PLoS biology · 2025Article
- Exploring vestibulocerebellum-vestibular nuclei-spinal trigeminal nucleus causals communication and TRPV2 ion channel in a mouse model of vestibular migraine.The journal of headache and pain · 2025Article
- Progesterone receptors regulate susceptibility to spreading depression.Experimental neurology · 2025Article
- Optogenetic cortical spreading depression originating from the primary visual cortex induces migraine-like pain and anxiety behaviors in freely moving C57BL/6 J mice.The journal of headache and pain · 2025Article
- Mechanisms underlying CSD initiation implicated by genetic mouse models of migraine.The journal of headache and pain · 2025Review
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
objectiveCortical spreading depression (SD) is an intense depolarization underlying migraine aura. Despite the weight of evidence linking SD to the pain phase of migraine, controversy remains over a causal role of SD in cephalgia because of the invasive nature of previous SD induction methods. To overcome this problem, we used a novel minimally invasive optogenetic SD induction method and examined the effect of SD on behavior.
methodsOptogenetic SD was induced as a single event or repeatedly every other day for 2 weeks. End points, including periorbital and hindpaw mechanical allodynia, mouse grimace, anxiety, and working memory, were examined in male and female mice.
resultsA single SD produced bilateral periorbital mechanical allodynia that developed within 1 hour and resolved within 2 days. Sumatriptan prevented periorbital allodynia when administered immediately after SD. Repeated SDs also produced bilateral periorbital allodynia that lasted 4 days and resolved within 2 weeks after the last SD. In contrast, the hindpaw withdrawal thresholds did not change after repeated SDs suggesting that SD-induced allodynia was limited to the trigeminal region. Moreover, repeated SDs increased mouse grimace scores 2 days after the last SD, whereas a single SD did not. Repeated SDs also increased thigmotaxis scores as a measure of anxiety. In contrast, neither single nor repeated SDs affected visuospatial working memory. We did not detect sexual dimorphism in any end point.
interpretationAltogether, these data show a clinically congruent causal relationship among SD, trigeminal pain, and anxiety behavior, possibly reflecting SD modulation of hypothalamic, thalamic, and limbic mechanisms. ANN NEUROL 2021;89:99-110.
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