Elsevier

The Journal of Pain

Volume 17, Issue 1, January 2016, Pages 1-13
The Journal of Pain

Original Report
Functional Connectivity Is Associated With Altered Brain Chemistry in Women With Endometriosis-Associated Chronic Pelvic Pain

Presented in part at the International Association for the Study of Pain Annual Scientific Meeting, August 2012, Milan, Italy and the Biennial Conference on Resting State/Brain Connectivity, September 2014, Boston, Massachusetts.
https://doi.org/10.1016/j.jpain.2015.09.008Get rights and content
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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

Endometriosis
chronic pelvic pain
neuroimaging
glutamate
functional connectivity

Cited by (0)

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.

1

Permanent address: Korea Institute of Oriental Medicine, Daejeon, Korea.

2

Permanent address: Department of Neurology, BG Universitätsklinikum Bergmannsheil, Ruhr Universität Bochum, Bochum, Germany.