Thalamocortical bistable switch as a theoretical model of fibromyalgia pathogenesis inferred from a literature survey
Open accessAbstract
Fibromyalgia (FM) is an unsolved central pain processing disturbance. We aim to provide a unifying model for FM pathogenesis based on a loop network involving thalamocortical regions, i.e., the ventroposterior lateral thalamus (VPL), the somatosensory cortex (SC), and the thalamic reticular nucleus (TRN). The dynamics of the loop have been described by three differential equations having neuron mean firing rates as variables and containing Hill functions to model mutual interactions among the loop elements. A computational analysis conducted with MATLAB has shown a transition from monostability to bistability of the loop behavior for a weakening of GABAergic transmission between TRN and VPL. This involves the appearance of a high-firing-rate steady state, which becomes dominant and is assumed to represent pathogenic pain processing giving rise to chronic pain. Our model is consistent with a bulk of literature evidence, such as neuroimaging and pharmacological data collected on FM patients, and with correlations between FM and immunoendocrine conditions, such as stress, perimenopause, chronic inflammation, obesity, and chronic dizziness. The model suggests that critical targets for FM treatment are to be found among immunoendocrine pathways leading to GABA/glutamate imbalance having an impact on the thalamocortical system.
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For b = 1, the thalamocortical loop system is monostable for a > 0.265, with a single basin of attraction and a low-firing-rate steady state.
“In our previous study, we have shown that for b = 1, i.e. a theoretical maximal value for the glutamatergic strength, the system is monostable for a>0.265, with a single basin of attraction and a low-firing-rate steady state (see Box 1).”
From Fibromyalgia pathogenesis explained by a neuroendocrine multistable model (2024) · cites this paper as [18]
In “Acquisition of bistability for inhibitory GABAergic weakening” (page unavailable), the paper reports a single low-firing-rate steady state and one basin of attraction before the bifurcation at a = 0.265. Our copy does not specify b = 1 or identify b as glutamatergic strength, so it does not support that condition attached to the result. (LLM, conf=0.84)
Experimental — accuracy not yet measuredThe thalamocortical loop system can globally behave as a monostable system for stronger GABAergic transmission, or as a bistable system for a weakening of GABAergic transmission.
“we have demonstrated that it can globally behave as a monostable system (see Box 1) (when the negative loop is dominant) for stronger GABAergic transmission, or as a bistable system (when the positive loop is dominant) for a weakening of GABAergic transmission [18].”
From Fibromyalgia pathogenesis explained by a neuroendocrine multistable model (2024) · cites this paper as [18]
At a = 0.265 there is a bifurcation point, so that if a goes below this value the system becomes bistable, acquiring an additional high-firing-rate steady state.
“At a = 0.265 there is a bifurcation point (see Box 1), so that if a goes below this value the system becomes bistable, acquiring an additional high-firing-rate steady state.”
From Fibromyalgia pathogenesis explained by a neuroendocrine multistable model (2024) · cites this paper as [18]
Fibromyalgia chronic pain depends on malfunctioning of a thalamocortical loop network.
“We have previously proposed that FM chronic pain depends on the malfunctioning of a thalamocortical loop network (Fig 1) [18].”
From Fibromyalgia pathogenesis explained by a neuroendocrine multistable model (2024) · cites this paper as [18]
The Hill coefficient for input-output neuron firing rate relationship of the thalamocortical model is 2.5.
“are higher than those derived for the input-output neuron firing rate relationship of our thalamocortical model, h = 2.5 [18]”
From Fibromyalgia pathogenesis explained by a neuroendocrine multistable model (2024) · cites this paper as [18]
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Fibromyalgia pathogenesis explained by a neuroendocrine multistable model
Demori, I., Losacco, S., Giordano, G., Mucci, V., Blanchini, F., & Burlando, B. (2024) · PLOS ONE · doi:10.1371/journal.pone.0303573 · Cited by 14 · see citing works
Self-citationDemori, I., Siriya, S., & Burlando, B. (2025) · Applied Sciences · doi:10.3390/app151910483 · Cited by 2 · see citing works
Self-citation
- Authors
- Demori, I., Giordano, G., Mucci, V., Losacco, S., Marinelli, L., Massobrio, P., Blanchini, F., & Burlando, B.
- Affiliations
- University of Genoa (IT)
- University of Trento (IT)
- Western Sydney University (AU)
- Ospedale Policlinico San Martino (IT)
- University of Udine (IT)
- Corresponding author
- Burlando, Bruno
- ORCID
- Venue
- Journal of Computational Neuroscience
- Published
- 2022-07-11
- Volume
- 50
- Issue
- 4
- Pages
- 471-484
- ISSN
- 0929-5313 (ISSN-L)
- 1573-6873
- PMC
- PMC9666334
- OpenAlex
- W4285012442
- Cited by
- 14
- References
- 123
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 6 · 2023: 2
- FWCI
- 1.79
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Journal of Computational Neuroscience (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Institutional Research Information System (Università degli Studi di Trento) (submittedVersion, cc-by)
- Institutional Research Information System (University of Udine) (submittedVersion, cc-by)
- CINECA IRIS Institutial Research Information System (University of Genoa) (submittedVersion, other-oa)
- Funders
- Università degli Studi di Genova (100006-2020-SA-FRA_001)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Fibromyalgia and Chronic Fatigue Syndrome Research
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Keywords
- fibromyalgia, thalamic reticular nucleus, somatosensory cortex, GABAergic neurotransmission, Hill function, chronic pain, central pain processing, stress, perimenopause, chronic inflammation, obesity, chronic dizziness
- MeSH terms
- Female, Fibromyalgia, Humans, Models, Neurological, Neural Pathways, Pain, Thalamic Nuclei, Thalamus
About these checks
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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