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The posterior medial cortex in urologic chronic pelvic pain syndrome: detachment from default mode network—a resting-state study from the MAPP Research Network

Martucci, Katherine T.a; Shirer, William R.b; Bagarinao, Epifanioa; Johnson, Kevin A.a; Farmer, Melissa A.c; Labus, Jennifer S.d; Apkarian, A. Vaniac; Deutsch, George; Harris, Richard E.f; Mayer, Emeran A.d; Clauw, Daniel J.f; Greicius, Michael D.b; Mackey, Sean C.a,*

doi: 10.1097/j.pain.0000000000000238
Research Paper

Altered resting-state (RS) brain activity, as a measure of functional connectivity (FC), is commonly observed in chronic pain. Identifying a reliable signature pattern of altered RS activity for chronic pain could provide strong mechanistic insights and serve as a highly beneficial neuroimaging-based diagnostic tool. We collected and analyzed RS functional magnetic resonance imaging data from female patients with urologic chronic pelvic pain syndrome (N = 45) and matched healthy participants (N = 45) as part of an NIDDK-funded multicenter project ( Using dual regression and seed-based analyses, we observed significantly decreased FC of the default mode network to 2 regions in the posterior medial cortex (PMC): the posterior cingulate cortex (PCC) and the left precuneus (threshold-free cluster enhancement, family-wise error corrected P < 0.05). Further investigation revealed that patients demonstrated increased FC between the PCC and several brain regions implicated in pain, sensory, motor, and emotion regulation processes (eg, insular cortex, dorsolateral prefrontal cortex, thalamus, globus pallidus, putamen, amygdala, hippocampus). The left precuneus demonstrated decreased FC to several regions of pain processing, reward, and higher executive functioning within the prefrontal (orbitofrontal, anterior cingulate, ventromedial prefrontal) and parietal cortices (angular gyrus, superior and inferior parietal lobules). The altered PMC connectivity was associated with several phenotype measures, including pain and urologic symptom intensity, depression, anxiety, quality of relationships, and self-esteem levels in patients. Collectively, these findings indicate that in patients with urologic chronic pelvic pain syndrome, regions of the PMC are detached from the default mode network, whereas neurological processes of self-referential thought and introspection may be joined to pain and emotion regulatory processes.

Supplemental Digital Content is Available in the Text.In chronic pelvic pain, the posterior cingulate cortex is functionally detached from the default mode network and instead joined to pain and emotion processing regions.

aDepartment of Anesthesiology, Perioperative and Pain Medicine, Division of Pain Medicine, Stanford University, Stanford, CA, USA

bDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA

cDepartment of Physiology, Northwestern University, Chicago, IL, USA

dDepartment of Medicine, David Geffen School of Medicine, Division of Digestive Diseases, University of California, Los Angeles, CA, USA

eDepartment of Radiology, University of Alabama at Birmingham, Birmingham, AL, USA

fDepartment of Anesthesiology, University of Michigan Ann Arbor, Ann Arbor, MI, USA

Corresponding author. Address: Department of Anesthesiology, Perioperative and Pain Medicine, Division of Pain Medicine, Stanford University, 1070 Arastradero Rd, Room 285, MC 5596, Palo Alto, CA 94304-1336, USA. Tel.: +650 498-6477; fax: +650 725-9642. E-mail address: (S. C. Mackey).

Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (

Received February 12, 2015

Received in revised form May 01, 2015

Accepted May 12, 2015

© 2015 International Association for the Study of Pain
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