Research Article: Impact of early adverse life events and sex on functional brain networks in patients with urological chronic pelvic pain syndrome (UCPPS): A MAPP Research Network study

Date Published: June 20, 2019

Publisher: Public Library of Science

Author(s): Arpana Gupta, Ravi R. Bhatt, Bruce D. Naliboff, Jason J. Kutch, Jennifer S. Labus, Priten P. Vora, Mher Alaverdyan, Andrew Schrepf, Susan Lutgendorf, Emeran A. Mayer, Jens Foell.


Pain is a highly complex and individualized experience with biopsychosocial components. Neuroimaging research has shown evidence of the involvement of the central nervous system in the development and maintenance of chronic pain conditions, including urological chronic pelvic pain syndrome (UCPPS). Furthermore, a history of early adverse life events (EALs) has been shown to adversely impact symptoms throughout childhood and into adulthood. However, to date, the role of EAL’s in the central processes of chronic pain have not been adequately investigated. We studied 85 patients (56 females) with UCPPS along with 86 healthy controls (HCs) who had resting-state magnetic resonance imaging scans (59 females), and data on EALs as a part of the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network Study. We used graph theory methods in order to investigate the impact of EALs on measures of centrality, which characterize information flow, communication, influence, and integration in a priori selected regions of interest. Patients with UCPPS exhibited lower centrality in the right anterior insula compared to HCs, a key node in the salience network. Males with UCPPS exhibited lower centrality in the right anterior insula compared the HC males. Females with UCPPS exhibited greater centrality in the right caudate nucleus and left angular gyrus compared to HC females. Males with UCPPS exhibited lower centrality in the left posterior cingulate, angular gyrus, middle temporal gyrus, and superior temporal sulcus, but greater centrality in the precuneus and anterior mid-cingulate cortex (aMCC) compared to females with UCPPS. Higher reports of EALs was associated with greater centrality in the left precuneus and left aMCC in females with UCPPS. This study provides evidence for disease and sex-related alterations in the default mode, salience, and basal ganglia networks in patients with UCPPS, which are moderated by EALs, and associated with clinical symptoms and quality of life (QoL).

Partial Text

Urologic Chronic Pelvic Pain Syndrome (UCPPS) is used to describe idiopathic chronic pelvic pain of urologic origin [1], including interstitial cystitis/bladder pain syndrome (IC/BPS), primarily diagnosed in women [2] and chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), a diagnosis exclusive to men [3]. The hallmark symptom is chronic pain in the pelvic region, urogenital floor or external genitalia, along with symptoms of urinary urgency and frequency [4,5]. UCPPS affects between 1.8% and 26.6% of the population [6,7], and it is thus a major healthcare problem with social and economic consequences [8,9]. However, despite various efforts directed towards identifying the underlying pathophysiology of UCPPS, our current understanding of the syndrome and effectiveness of available treatments remains limited [10]. One of the goals of the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network, a multi-site project funded by the National Institute of Diabetes and Digestive and Kidney Diseases [10,11], is to identify alterations in brain networks in affected patients which may play a role in symptom generation.

We identified group differences in measures of centrality in specific regions associated with UCPPS that are moderated by the presence of self-reported early life trauma. In most cases, this moderation was sex-specific. In our multi-site sample, females with UCPPS reported more EALs than female HCs, but there were no differences in EALs between males with UCPPS and male HCs, a finding consistent with previous analyses within the MAPP Research Network [29]. As previously reported, patients with UCPPS exhibited lower levels of quality of life, and greater pain symptom severity and urinary symptom severity compared to HCs. There was an overall disease-dependent association on measures of centrality with UCPPS patients having lower centrality in the anterior insula compared to HCs. EALs did have a sex-dependent association in the salience network, with greater EALs being associated with lower strength in the anterior mid-cingulate cortex in males with UCPPS, but greater in females with UCPPS. Greater EALs were mostly associated with lower centrality in the default mode network in males (except eigenvector centrality in the precuneus) but showed more nuanced results in females–differing by temporal sulci. This suggests that brain mechanisms in females, even within the default mode network, can contribute specifically to their observed symptoms.




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