Functional Connectivity Is Associated With Altered Brain Chemistry in Women With Endometriosis-Associated Chronic Pelvic Pain
Open accessAbstract
Unlabelled In contrast to women with relatively asymptomatic endometriosis, women with endometriosis-associated chronic pelvic pain (CPP) exhibit nonpelvic hyperalgesia and decreased gray matter volume in key neural pain processing regions. Although these findings suggest central pain amplification in endometriosis-associated CPP, the underlying changes in brain chemistry and function associated with central pain amplification remain unknown. We performed proton spectroscopy and seed-based resting functional connectivity magnetic resonance imaging to determine whether women with endometriosis display differences in insula excitatory neurotransmitter concentrations or intrinsic brain connectivity to other pain-related brain regions. Relative to age-matched pain-free controls, women with endometriosis-associated CPP displayed increased levels of combined glutamine-glutamate (Glx) within the anterior insula and greater anterior insula connectivity to the medial prefrontal cortex (mPFC). Increased connectivity between these regions was positively correlated with anterior insula Glx concentrations (r = .87), as well as clinical anxiety (r = .61, P = .02), depression (r = .60, P = .03), and pain intensity (r = .55, P = .05). There were no significant differences in insula metabolite levels or resting-state connectivity in endometriosis patients without CPP versus controls. We conclude that enhanced anterior insula glutamatergic neurotransmission and connectivity with the mPFC, key regions of the salience and default mode networks, may play a role in the pathophysiology of CPP independent of the presence of endometriosis.Perspective Similar to other chronic pain conditions, endometriosis-associated pelvic pain is associated with altered brain chemistry and function in pain processing regions. These findings support central pain amplification as a mechanism of chronic pelvic pain, and clinicians should consider the use of adjunctive therapies that target central pain dysfunction in these women.
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Central changes are observed in endometriosis: alterations in behavioral and central response to noxious stimulation, changes in brain structure, altered activity of both HPA and autonomic nervous system and psychological distress, with larger volume in regions involved in pain modulation and endocrine function regulation.
“a number of central changes are observed: alterations in the behavioral and central response to noxious stimulation, changes in brain structure, altered activity of both the HPA and the autonomic nervous system and psychological distress [131], with larger volume in regions involved in pain modulation and endocrine function regulation [137–139].”
From Hormonal treatments for endometriosis: The endocrine background (2022) · cites this paper as [139]
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredIncreased concentration of glutamine and glutamate within the anterior insula and greater neuronal connectivity from the anterior insula to the medial prefrontal cortex positively correlate with pain intensity, clinical anxiety, and depression in endometriosis patients.
“Furthermore, As-Sanie et al. demonstrated that increased concentration of glutamine and glutamate within the anterior insula and greater neuronal connectivity from the anterior insula to the medial prefrontal cortex positively correlated with not only pain intensity, but also clinical anxiety and depression in patients (60).”
From Biomarkers in endometriosis: Challenges and opportunities (2017) · cites this paper as [60]
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References 69 · Cited by 199
Research works printed but not linked: 2
- [12]Brett M Anton JL Valabregue R Poline JB Region of interest analysis using an SPM toolbox [abstract] Presented at the 8th International Conference on Functional Mapping of the Human Brain June 2–6, 2002 Sendai, Japan Available on CD-ROM in NeuroImage 16 2
- [17]Cleeland C Measurement of pain by subjective report Issues in pain measurement: advances in pain research and therapy Chapman C Loeser J Raven Press New York, NY 1989 391 403
- Authors
- As-Sanie, S., Kim, J., Schmidt-Wilcke, T., Sundgren, P. C., Clauw, D. J., Napadow, V., & Harris, R. E.
- Affiliations
- Massachusetts General Hospital (US)
- University of Michigan (US)
- Venue
- The Journal of Pain
- Publisher
- Elsevier BV
- Published
- 2016-01
- Volume
- 17
- Issue
- 1
- Pages
- 1-13
- ISSN
- 1526-5900 (ISSN-L)
- PMC
- PMC4698023
- OpenAlex
- W2213680767
- Cited by
- 199
- References
- 69
- Citations by year
- 2026: 19 · 2025: 28 · 2024: 17 · 2023: 19 · 2022: 17 · 2021: 23 · 2020: 21 · 2019: 19 · 2018: 15 · 2017: 14 · 2016: 7
- FWCI
- 13.68
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Pain (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- National Institutes of Health (UL1TR000433, 1s10od012240-01a1, KL2TR000434)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR064367)
- National Center for Research Resources (KL2RR024987, M01RR001066, UL1RR024986, M01RR000042)
- National Center for Advancing Translational Sciences
- National Center for Complementary and Integrative Health (P01AT006663, R01AT007550)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (K12HD001438)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Endometriosis Research and Treatment
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Keywords
- endometriosis, chronic pelvic pain, functional connectivity, anterior insula, glutamate/glutamine, glutamatergic neurotransmission, medial prefrontal cortex, anxiety, depression, salience network, default mode network, 1H NMR, resting-state functional connectivity
- MeSH terms
- Adult, Cerebral Cortex, Endometriosis, Female, Glutamine, Humans, Image Processing, Computer-Assisted, Middle Aged, Neural Pathways, Magnetic Resonance Spectroscopy, Pelvic Pain, Glutamic Acid, Young Adult, Chronic Pain
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