Background & Aims

Fluctuations in pain intensity for individuals with chronic pain conditions are a common but poorly understood phenomenon. Identifying the importance of these fluctuations as well as associated changes in brain activity that underlie these fluctuations have the potential to identify neural factors that may process and amplify pain and are critical to understanding individual variability. In this analysis, we examined data from patients with urologic chronic pelvic pain syndrome (UCPPS) in the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network Symptom Patterns Study (SPS). We aimed to identify the changes in functional connectivity underlying fluctuations in pelvic pain severity and whether this relationship would be moderated by important clinical phenotypes in UCPPS such as presence of multisite pain.

Methods

Data was collected across six sites from 492 UCPPS patients (315 female, 177 male). We collected average self-reported pain, clinical questionnaire data, and resting-state functional magnetic resonance imaging (rs-fMRI). We assessed the link between pain and functional connectivity by regressing connectivity features onto pain measures from one baseline and three follow-up visits (6, 18, 36 months) in each patient. We ran additional regressions with an interaction term between pain and each of the clinical characteristics of interest (depression, anxiety, multisite pain, pain catastrophizing, and painDETECT scores) to determine their impact on the relationship between pain and functional connectivity. Additionally, we analyzed the impact of pain on flare-status and physical/mental functioning by regressing it onto the 12-Item Short-Form Health Survey’s component scores and whether patients reported being in a flare (yes/no). p-values for key effects were FDR corrected (q<0.05).

Results

Participants experienced fluctuations in average self-reported pain across four visits (36-month timeline) with variability between subjects. Areas of connectivity most likely to vary as a person experienced more or less pelvic pain were sensorimotor regions, bilateral insula, posterior and anterior cingulate, and medial prefrontal cortex. These areas include nodes in the salience network and sensorimotor areas related to the painful body region (pelvis). Additionally, we found that of the five clinical markers of interest, only multisite pain significantly modified the relationship between pain and connectivity. Areas where the relationship between pain and brain activity was most likely to be modified by multisite pain ratings were sensorimotor regions, the precuneus, and superior frontal gyrus. Additional analyses of self-reported daily function and pain flare-up support the use of pain fluctuations for study participants.

Conclusions

Long-term symptom profiles in UCPPS are generally stable for differing symptom burdens (in this case high and low pain), but still fluctuate within individuals over time as suggested in previous work [1,3]. Our imaging findings suggest that functional connectivity changes in a common set of regions (primarily in somatosensory/motor and salience networks) underlie the fluctuations in pain that UCPPS patients experience. While these regions include medial sensorimotor clusters consistent with the painful body site (pelvis), denser lateral clusters in the sensorimotor regions may overlap with previously identified integrative hubs representing multiple body regions [2]. Additionally, we find that multisite pain may be uniquely important for modifying the relationship between brain activity and individual pain ratings. This may indicate that multisite pain is a particularly good marker of conditions where pain is centrally amplified.

References

[1] Bradley CS, Gallop R, Sutcliffe S, Kreder KJ, Lai HH, Clemens JQ, Naliboff BD, Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network. Long-Term Symptom Trajectories in Urologic Chronic Pelvic Pain Syndrome: A MAPP Research Network Study. Urology 2022;169:58–64.

[2] Gordon EM, Chauvin RJ, Van AN, Rajesh A, Nielsen A, Newbold DJ, Lynch CJ, Seider NA, Krimmel SR, Scheidter KM, Monk J, Miller RL, Metoki A, Montez DF, Zheng A, Elbau I, Madison T, Nishino T, Myers MJ, Kaplan S, Badke D’Andrea C, Demeter DV, Feigelis M, Ramirez JSB, Xu T, Barch DM, Smyser CD, Rogers CE, Zimmermann J, Botteron KN, Pruett JR, Willie JT, Brunner P, Shimony JS, Kay BP, Marek S, Norris SA, Gratton C, Sylvester CM, Power JD, Liston C, Greene DJ, Roland JL, Petersen SE, Raichle ME, Laumann TO, Fair DA, Dosenbach NUF. A somato-cognitive action network alternates with effector regions in motor cortex. Nature 2023;617:351–359.

[3] Stephens-Shields AJ, Clemens JQ, Jemielita T, Farrar J, Sutcliffe S, Hou X, Landis JR, MAPP Research Network. Symptom Variability and Early Symptom Regression in the MAPP Study: A Prospective Study of Urological Chronic Pelvic Pain Syndrome. J Urol 2016;196:1450–1455.

Presenting Author

Natalie J. McLain

Poster Authors

Natalie McLain

BSc, BA

University of Southern California

Lead Author

E-mail

Andrew Schrepf

University of Michigan

Lead Author

E-mail

Bruce Naliboff

PhD

University of California Los Angeles

Lead Author

E-mail

Steven Harte

PhD

University of Michigan Chronic Pain and Fatigue Research Center

Lead Author

E-mail

Larissa Rodriguez

MD

Cornell University

Lead Author

E-mail

Robert Moldwin

MD

Hofstra University-Northwell Health

Lead Author

E-mail

David Williams

MD

University of Michigan

Lead Author

E-mail

John Farrar

Univ of PA

Lead Author

E-mail

Richard Harris

PhD

University of Michigan

Lead Author

E-mail

Theresa Spitznagle

PT

Washington University in St. Louis

Lead Author

E-mail

Quentin Clemens

MD

University of Michigan

Lead Author

E-mail

Chris Mullins

PhD

National Institutes of Health

Lead Author

E-mail

Jason Kutch

PhD

University of Southern California

Lead Author

E-mail

Topics

  • Pain Imaging