Chronic pain: lost inhibition?

Henderson, Luke A.; Peck, Chris C.; Petersen, Esben T.; Rae, Caroline D.; Youssef, Andrew M.; Reeves, Jenna M.; Wilcox, Sophie L.; Akhter, Rahena; Murray, Greg M.; Gustin, Sylvia M.

doi:10.1523/jneurosci.0174-13.2013

Cited by 180Pain Mechanisms and TreatmentsPain Management and TreatmentPain Management and Placebo Effect

Chronic pain: lost inhibition?

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Henderson, Luke A., Peck, Chris C., Petersen, Esben T., Rae, Caroline D., Youssef, Andrew M., Reeves, Jenna M., Wilcox, Sophie L., Akhter, Rahena +2 more·2013·The Journal of Neuroscience

DOI 10.1523/jneurosci.0174-13.2013PMC PMC6619566

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Abstract

Human brain imaging has revealed that acute pain results from activation of a network of brain regions, including the somatosensory, insular, prefrontal, and cingulate cortices. In contrast, many investigations report little or no alteration in brain activity associated with chronic pain, particularly neuropathic pain. It has been hypothesized that neuropathic pain results from misinterpretation of thalamocortical activity, and recent evidence has revealed altered thalamocortical rhythm in individuals with neuropathic pain. Indeed, it was suggested nearly four decades ago that neuropathic pain may be maintained by a discrete central generator, possibly within the thalamus. In this investigation, we used multiple brain imaging techniques to explore central changes in subjects with neuropathic pain of the trigeminal nerve resulting in most cases (20 of 23) from a surgical event. Individuals with chronic neuropathic pain displayed significant somatosensory thalamus volume loss (voxel-based morphometry) which was associated with decreased thalamic reticular nucleus and primary somatosensory cortex activity (quantitative arterial spin labeling). Furthermore, thalamic inhibitory neurotransmitter content was significantly reduced (magnetic resonance spectroscopy), which was significantly correlated to the degree of functional connectivity between the somatosensory thalamus and cortical regions including the primary and secondary somatosensory cortices, anterior insula, and cerebellar cortex. These data suggest that chronic neuropathic pain is associated with altered thalamic anatomy and activity, which may result in disturbed thalamocortical circuits. This disturbed thalamocortical activity may result in the constant perception of pain.

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The model fits data about the presence of GABA-glutamate unbalance and the finding of glutamic acid decarboxylase decrease in FM patients.
“Second, it fits data about the presence of GABA-glutamate unbalance [136–138], and the finding of glutamic acid decarboxylase decrease in FM patients [139].”
From Fibromyalgia pathogenesis explained by a neuroendocrine multistable model (2024) · cites this paper as [138]
The citation is attached to the claimed decrease in glutamic acid decarboxylase in fibromyalgia patients. The Thalamic GABA levels section instead reports lower thalamic GABA in patients with painful trigeminal neuropathy; searches for glutamic acid decarboxylase and fibromyalgia found no passage reporting the cited finding. Page numbers were not available in our copy. (LLM, conf=0.78)
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The relationship between thalamic GABA content and resting cortical rhythm in neuropathic pain
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Chronic Neuropathic Pain: It's about the Rhythm
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Authors: Henderson, L. A., Peck, C. C., Petersen, E. T., Rae, C. D., Youssef, A. M., Reeves, J. M., Wilcox, S. L., Akhter, R., Murray, G. M., & Gustin, S. M.
Affiliations: The University of Sydney (AU)
University Medical Center Utrecht (NL)
Neuroscience Research Australia (AU)
ORCID: Henderson, Luke A.
Petersen, Esben T.
Rae, Caroline D.
Youssef, Andrew M.
Reeves, Jenna M.
Akhter, Rahena
Murray, Greg M.
Gustin, Sylvia M.
Venue: The Journal of Neuroscience
Publisher: Society for Neuroscience
Published: 2013-04-24
Volume: 33
Issue: 17
Pages: 7574-7582
ISSN: 0270-6474 (ISSN-L)
1529-2401
DOI: 10.1523/jneurosci.0174-13.2013
PMC: PMC6619566
OpenAlex: W2112900258
Cited by: 180
References: 56
Citations by year: 2026: 8 · 2025: 10 · 2024: 11 · 2023: 14 · 2022: 16 · 2021: 29 · 2020: 15 · 2019: 12 · 2018: 12 · 2017: 13 · 2016: 12 · 2015: 9 · 2014: 13 · 2013: 6
FWCI: 9.26
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-sa
creativecommons.org/licenses/by-nc-sa/4.0/ (vor, 183 d)
Locations: Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Charles Sturt University Research Output (CRO) (submittedVersion, other-oa)
ORBi (University of Liège) (submittedVersion)
Funders: Medical Research Council
National Health and Medical Research Council
Topics: Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Treatment
Life Sciences › Neuroscience › Cognitive Neuroscience › Pain Management and Placebo Effect
Keywords: chronic neuropathic pain, trigeminal neuralgia, somatosensory thalamus, thalamic reticular nucleus, thalamocortical circuits, thalamic inhibition, somatosensory cortex, anterior insula, cerebellum, functional connectivity, pain perception
MeSH terms: Adult, Cerebrovascular Circulation, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Neural Inhibition, Pain Measurement, Trigeminal Nerve Diseases, Chronic Pain

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Chronic pain: lost inhibition?

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