Resting-state functional connectivity predicts longitudinal pain symptom change in urologic chronic pelvic pain syndrome: a MAPP network study

Kutch, Jason J.; Labus, Jennifer S.; Harris, Richard E.; Martucci, Katherine T.; Farmer, Melissa A.; Fenske, Sonja J.; Fling, Connor; Ichesco, Eric; Peltier, Scott; Petre, Bogdan; Guo, Wensheng; Hou, Xiaoling; Stephens, Alisa; Mullins, Chris; Clauw, Daniel J.; Mackey, Sean; Apkarian, A. Vania; Landis, J. Richard; Mayer, Emeran A.

doi:10.1097/j.pain.0000000000000886

Cited by 56 publications

(52 citation statements)

References 47 publications

(79 reference statements)

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“…In a multi-site study of UCPPS patients, the severity of ELS was correlated with greater widespread pain and negative mood, and was inversely associated with likelihood of symptomatic improvement (3). Neuroimaging studies in the same cohort of UCPPS patients revealed significant changes in gray matter volume, neurochemical concentration, and functional connectivity that are correlated with widespreadness of pain and comorbid mood disorder (4)(5)(6)(7)(8)(9). Further analysis showed both sex-and ELS-dependent effects in discreet pain-processing regions (10), suggesting that ELS may specifically predispose patients to greater symptom burden and comorbidity.…”

Section: Introductionmentioning

confidence: 99%

Voluntary wheel running improves outcomes in an early life stress-induced model of urologic chronic pelvic pain syndrome in male mice

Fuentes

Jones

Brake

et al. 2020

Preprint

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Patients with a history of early life stress (ELS) exposure have an increased risk of developing chronic pain and mood disorders later in life. The severity of ELS in patients with urologic chronic pelvic pain syndrome (UCPPS) is directly correlated with symptom severity and increased comorbidity, and is inversely related to likelihood of improvement. Voluntary exercise improves chronic pain symptoms and our group and others have shown that voluntary wheel running can improve outcomes in stress-induced UCPPS models, suggesting that exercise may negate some of the outcomes associated with ELS. Here we provide further evidence that voluntary wheel running can attenuate increased perigenital mechanical sensitivity, bladder output, and mast cell degranulation in the bladder and prostate in male mice that underwent neonatal maternal separation (NMS). Sedentary male NMS mice had reduced serum corticosterone, which was not impacted by voluntary wheel running, although stress-related regulatory gene expression in the hypothalamus and hippocampus was significantly increased following exercise. Neurogenesis in the dentate gyrus of the hippocampus was diminished in sedentary NMS mice and significantly increased in both exercised naïve and NMS mice. Sucrose consumption increased in exercised naïve but not NMS mice, and anxiety behaviors measured on an elevated plus maze were increased following exercise. Together these data suggest that voluntary wheel running is sufficient to normalize many of the UCPPS-related outcomes resulting from NMS. Exercise also increased hippocampal neurogenesis and stress-related gene expression within the hypothalamic-pituitary-adrenal axis, further supporting exercise as a non-pharmacological intervention for attenuating outcomes related to ELS exposure.

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Section: Introductionmentioning

confidence: 99%

Voluntary wheel running improves outcomes in an early life stress-induced model of urologic chronic pelvic pain syndrome in male mice

Fuentes

Jones

Brake

et al. 2020

Preprint

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“…Altered brain activity in chronic pain occurs in response to various innocuous and noxious stimuli (for example, refs. 6 and 7), as well as during resting-state functional magnetic resonance imaging (rs-fMRI) measured in terms of functional connectivity (8,9), functional networks (10,11), and low-frequency oscillatory power (12)(13)(14). However, the complex underlying CNS processes that contribute to the initiation and maintenance of chronic pain conditions such as fibromyalgia remain unclear.…”

Section: Introductionmentioning

confidence: 99%

Altered Cervical Spinal Cord Resting‐State Activity in Fibromyalgia

Martucci

Weber

Mackey

2019

Arthritis & Rheumatology

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Objective Altered afferent input and central neural modulation are thought to contribute to fibromyalgia symptoms, and these processes converge within the spinal cord. We undertook this study to investigate the hypothesis that, using resting‐state functional magnetic resonance imaging (rs‐fMRI) of the cervical spinal cord, we would observe altered frequency‐dependent activity in fibromyalgia. Methods Cervical spinal cord rs‐fMRI was conducted in fibromyalgia patients (n = 16) and healthy controls (n = 17). We analyzed the amplitude of low‐frequency fluctuations (ALFF), a measure of low‐frequency oscillatory power, for frequencies of 0.01–0.198 Hz and frequency sub‐bands to determine regional and frequency‐specific alterations in fibromyalgia. Functional connectivity and graph metrics were also analyzed. Results As compared to healthy controls (n = 14), greater ventral and lesser dorsal mean ALFF of the cervical spinal cord was observed in fibromyalgia patients ( n = 15) (uncorrected P < 0.05) for frequencies of 0.01–0.198 Hz and all sub‐bands. Additionally, lesser mean ALFF within the right dorsal quadrant (corrected P < 0.05) for frequencies of 0.01–0.198 Hz and sub‐band frequencies of 0.073–0.198 Hz was observed in fibromyalgia. Regional mean ALFF was not correlated with pain; however, regional lesser mean ALFF was correlated with fatigue in patients (r = 0.763, P = 0.001). Functional connectivity and graph metrics were similar between groups. Conclusion Our results indicate unbalanced activity between the ventral and dorsal cervical spinal cord in fibromyalgia. Increased ventral neural processes and decreased dorsal neural processes may reflect the presence of central sensitization and contribute to fatigue and other bodily symptoms in fibromyalgia.

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“…A different approach is to measure the dynamic brain connectivity, which varies over time, to enable identification of connectivity patterns that vary with reported levels of ongoing pain. This approach has revealed changes in the default mode and salience brain networks in chronic pain states [107][108][109] . However, a potential confounding factor is the possibility that the judgement and reporting of ongoing pain causes a detectable change in brain processing.…”

Section: O N S E N S U S S Tat E M E N Tmentioning

confidence: 99%

Brain imaging tests for chronic pain: medical, legal and ethical issues and recommendations

et al. 2017

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624 | OCTOBER 2017 | VOLUME 13 www.nature.com/nrneurol CONSENSUS STATEMENT © 2 0 1 7 M a c m i l l a n P u b l i s h e r s L i m i t e d , p a r t o f S p r i n g e r N a t u r e . A l l r i g h t s r e s e r v e d . NeuroethicsA field that studies the implications of neuroscience for human self-understanding, ethics, and policy. Arterial spin labellingAn MRI-based brain imaging technique that detects cerebral blood flow based on magnetic tagging of blood.Nevertheless, diverse groups -including patients, researchers, clinicians, pharmaceutical and medical device companies, insurers and the legal communityseek methods for evaluating chronic pain besides selfreporting. Patients seek objective testing to demonstrate the reality of an invisible condition that is sometimes subject to doubt, researchers seek brain imaging markers that provide scientific, diagnostic and prognostic information that cannot be provided by patient self-reporting, and legal representatives and officials seek techniques to supplement self-reporting and objectively support or challenge claims related to chronic pain. Brain imaging technologies, including functional MRI (fMRI), PET, EEG and magnetoencephalography (MEG), have the potential to provide objective measurements of patterns of brain activity that underlie perceptual experiences (BOX 1). Consequently, some people are looking to brain imaging to provide a window into the experience of chronic pain, particularly because testimony based on fMRI was deemed to be admissible as evidence of pain in a 2015 state trial court in the USA 10,11 . This case was highly publicized, although the judgement was not published so no legal precedent was set, and the grounds on which the fMRI evidence was admitted were criticized by established experts in brain imaging studies of pain 10,11 . In this context, the development of a brain imaging test for chronic pain [12][13][14] has real-world consequences, so appropriate criteria for the use of such a test must be defined. Importantly, the way in which brain imaging evidence might be implemented in legal cases strongly depends on laws that vary greatly between countries. Therefore, examination of the capability of so-called 'pain-o-meter' brain imaging tests is critical, as is consideration of the use of such technology in light of societal views, neuroethics and legal issues. Thus, the aims of this Consensus Statement are to recommend criteria for the evaluation of neuroimaging measures of chronic pain, and to discuss the technical, biological, neuroethical and legal challenges related to establishing brain-based tests for chronic pain. MethodsA presidential task force of the International Association for the Study of Pain (IASP) was established in 2015 to examine the feasibility of a brain-imaging-based diagnostic test for chronic pain. The task force had three purposes: to consider the capacity of brain imaging (in particular fMRI), on the basis of its technical and physiological constraints, to detect whether an individual has chronic pain; to place th...

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Resting-state functional connectivity predicts longitudinal pain symptom change in urologic chronic pelvic pain syndrome: a MAPP network study

Cited by 56 publications

References 47 publications

Voluntary wheel running improves outcomes in an early life stress-induced model of urologic chronic pelvic pain syndrome in male mice

Voluntary wheel running improves outcomes in an early life stress-induced model of urologic chronic pelvic pain syndrome in male mice

Altered Cervical Spinal Cord Resting‐State Activity in Fibromyalgia

Brain imaging tests for chronic pain: medical, legal and ethical issues and recommendations

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