Highlights
- •Chronic pelvic pain is a symptom in some, but not all, women with endometriosis.
- •The mechanism by which only some women with endometriosis experience pain is not understood.
- •Endometriosis-associated pelvic pain was associated with altered brain chemistry and function.
- •These differences were not identified in a pain-free endometriosis subgroup.
- •Central nervous system changes likely contribute to the mechanism of endometriosis pain.
Abstract
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.
Key words
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Article info
Publication history
Published online: October 05, 2015
Accepted:
September 23,
2015
Received in revised form:
September 9,
2015
Received:
April 29,
2015
Footnotes
This study was funded by NIH K12HD001438, NIH UL1RR024986, NIH 1S10OD012240-01A1, and the Bayer Droegemueller Award in Clinical Research. T.S.-W. was supported by a grant from the DFG (Deutsche Forschungsgemeinschaft, GZ: SchM 2665/1). V.N. was supported by NCCAM, NIH: P01-AT006663, R01-AT007550; NIAMS, NIH: R01-AR064367. R.E.H. was supported by the Dana Foundation, the Department of Defense (Army grant: DAMD-W81XWH-07-2-0050), GCRC M01-RR-01066, and NIH: 1R01 AT007550. J.K. was supported by a grant of the Korea Institute of Oriental Medicine (K15050). R.E.H. has previously consulted for Pfizer, Inc. D.J.C. has received grants/research support from Pfizer, Inc and Forest Laboratories. He has been a consultant for and served on advisory boards for Pfizer, Inc, Eli Lilly and Company, Forest Laboratories, Inc, Cypress Bioscience, Inc, Pierre Fabre Pharmaceuticals, UCB, and AstraZeneca. All other authors have no conflicts of interest to disclose.
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© 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.
