ArticleThe journal of headache and pain2021
Interleukin-6 induces spatially dependent whole-body hypersensitivity in rats: implications for extracephalic hypersensitivity in migraine.
Article in The journal of headache and pain, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 24 citations in OpenAlex.
- CGRP-provoked headache is associated with a neuroimmune signature in idiopathic intracranial hypertension.The journal of headache and pain · 2026Trial
- Higher Circulating IL-6 levels as a predictor for poor outcome after migraine preventive treatment: a prospective study.The journal of headache and pain · 2025Trial
- TRPM3 activation causes CGRP release in trigeminal neurons: Implications for migraine mechanisms.Headache · 2026Article
- Macrophages and iNOS contribute to the effects of dural prolactin and repeated stress in mouse migraine models.The journal of headache and pain · 2025Article
- Antinociceptive and anti-inflammatory effects of a formulation based onJournal of oral & facial pain and headache · 2025Article
- Serum inflammatory cytokines as biomarkers for predicting chronic migraine transformation: a systematic review of randomized controlled trials.Annals of medicine and surgery (2012) · 2025Article
- Peripheral macrophages contribute to nociceptor priming in mice with chronic intermittent hypoxia.Science signaling · 2024Article
- Valproate attenuates somatic hyperalgesia induced by orofacial inflammation combined with stress through inhibiting spinal IL-6 and STAT1 phosphorylation.Brain research bulletin · 2024Article
- Independent causal effect of migraines on Alzheimer's disease risk: a multivariate Mendelian randomization study.Frontiers in neurology · 2024Article
- Experimental and Clinical Investigation of Cytokines in Migraine: A Narrative Review.International journal of molecular sciences · 2023Review
- Olfactory training reduces pain sensitivity in children and adolescents with primary headaches.Frontiers in pain research (Lausanne, Switzerland) · 2023Article
- Associations between Fatty Acid Intake and Tension-Type Headache: A Cross-Sectional Study.Journal of clinical medicine · 2022Article
- Review
- Dural Immune Cells, CGRP, and Migraine.Frontiers in neurology · 2022Review
- Unpredictable Sound Stress Model Causes Migraine-Like Behaviors in Mice With Sexual Dimorphism.Frontiers in pharmacology · 2022Article
- Sexual dimorphism in functional pain syndromes.Science translational medicine · 2021Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
backgroundMigraine is a complex neurological disorder that is characterized by throbbing head pain, increased sensitivity to light, sound, and touch, as well as nausea and fatigue. It is one of the most common and most disabling disorders globally but mechanisms causing migraine are poorly understood. While head pain is a typical feature of attacks, they also often present with cutaneous hypersensitivity in the rest of the body. In contrast, primary pain conditions in the lower parts of the body are less commonly associated with cephalic hypersensitivity. Previous studies indicate that application of stimuli to the meninges of rodents causes cutaneous facial as well as hindpaw hypersensitivity. In the present study, we asked whether widespread hypersensitivity is a unique feature of dural stimulation or whether body-wide responses occur similarly when the same stimulus is given in other locations.
methodsRats were given the same dose of IL-6 either via dural, intraplantar, subcutaneous, intramuscular, intracisternal, or intrathecal injection. Cutaneous facial and hindpaw allodynia was assessed using Von Frey following injection into each location.
resultsHindpaw allodynia was observed following dural and intraplantar injection of IL-6 in both males and females. Hindpaw allodynia was only observed in females following intracisternal and intrathecal IL-6 injections. In contrast, facial allodynia was only observed in either sex following dural and intracisternal injections, which would activate meningeal afferents and the trigeminal nucleus caudalis (TNC), respectively.
conclusionsHere we show that while stimulation of upper body regions with IL-6 including the meninges and brainstem can cause widespread hypersensitivity spreading to the paws, similar stimulation of the lower body does not cause the spread of hypersensitivity into the head. These data are consistent with the observations that whole body hypersensitivity is specific to conditions such as migraine where pain is present in the head and they may provide insight into co-morbid pain states associated with migraine.
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