Brain network alterations in the inflammatory soup animal model of migraine
Open accessAbstract
Advances in our understanding of the human pain experience have shifted much of the focus of pain research from the periphery to the brain. Current hypotheses suggest that the progression of migraine depends on abnormal functioning of neurons in multiple brain regions. Accordingly, we sought to capture functional brain changes induced by the application of an inflammatory cocktail known as inflammatory soup (IS), to the dura mater across multiple brain networks. Specifically, we aimed to determine whether IS alters additional neural networks indirectly related to the primary nociceptive pathways via the spinal cord to the thalamus and cortex. IS comprises an acidic combination of bradykinin, serotonin, histamine and prostaglandin PGE2 and was introduced to basic pain research as a tool to activate and sensitize peripheral nociceptors when studying pathological pain conditions associated with allodynia and hyperalgesia. Using this model of intracranial pain, we found that dural application of IS in awake, fully conscious, rats enhanced thalamic, hypothalamic, hippocampal and somatosensory cortex responses to mechanical stimulation of the face (compared to sham synthetic interstitial fluid administration). Furthermore, resting state MRI data revealed altered functional connectivity in a number of networks previously identified in clinical chronic pain populations. These included the default mode, sensorimotor, interoceptive (Salience) and autonomic networks. The findings suggest that activation and sensitization of meningeal nociceptors by IS can enhance the extent to which the brain processes nociceptive signaling, define new level of modulation of affective and cognitive responses to pain; set new tone for hypothalamic regulation of autonomic outflow to the cranium; and change cerebellar functions.
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Psychosocial processes can be pre-existing vulnerability factors or can emerge in response to ongoing pain.
“In the first category, psychosocial processes either exist within an individual as pre-existing “vulnerability” factor [e.g., distress20–22, trauma23, 24] or emerge for the first time in response to the experience of ongoing pain [e.g., fear-avoidance behavior 25, self-efficacy26, 27].”
From Evaluating psychosocial contributions to chronic pain outcomes (2018) · cites this paper as [27]
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Evaluating psychosocial contributions to chronic pain outcomes
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Self-citation
- Authors
- Becerra, L., Bishop, J., Barmettler, G., Kainz, V., Burstein, R., & Borsook, D.
- Affiliations
- Boston Children's Hospital (US)
- Beth Israel Deaconess Medical Center (US)
- Corresponding author
- Becerra, Lino
- Venue
- Brain Research
- Publisher
- Elsevier BV
- Published
- 2017-04
- Volume
- 1660
- Pages
- 36-46
- ISSN
- 0006-8993 (ISSN-L)
- PMC
- PMC5731648
- OpenAlex
- W2583306930
- Cited by
- 40
- References
- 88
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 2 · 2023: 3 · 2022: 6 · 2021: 2 · 2020: 5 · 2019: 10 · 2018: 5 · 2017: 3
- FWCI
- 5.16
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Brain Research (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Migraine Research Foundation
- Louis Herlands Fund for Pain Research (NS069847, NS079678, K24-NS064050)
- GlaxoSmithKline
- NIH
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Migraine and Headache Studies
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Treatment
- Keywords
- migraine, inflammatory soup, meningeal nociceptors, dura mater, functional connectivity, resting-state fMRI, thalamus, hypothalamus, hippocampus, somatosensory cortex, default mode network, sensorimotor network, salience network, bradykinin, serotonin, histamine, prostaglandin E2
- MeSH terms
- Animals, Brain, Brain Mapping, Disease Models, Animal, Hot Temperature, Magnetic Resonance Imaging, Male, Migraine Disorders, Neural Pathways, Physical Stimulation, Rest, Rats, Sprague-Dawley, Touch Perception, Nociceptive Pain
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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