Brain connectivity Patterns Dissociate action of specific Acupressure Treatments in Fatigued Breast cancer survivors

Funding This work was supported by grants R01 CA151445 and 2UL1 TR000433-06 from the National Institutes of Health. The funding source had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. We thank the expert assistance by Dr. Bradley Foerster in acquisition of 1H-MRS and fMRI data.Peer reviewedPublisher PD

Resting state connectivity correlates with drug and placebo response in fibromyalgia patients

AbstractFibromyalgia is a chronic pain syndrome characterized by widespread pain, fatigue, and memory and mood disturbances. Despite advances in our understanding of the underlying pathophysiology, treatment is often challenging. New research indicates that changes in functional connectivity between brain regions, as can be measured by magnetic resonance imaging (fcMRI) of the resting state, may underlie the pathogenesis of this and other chronic pain states. As such, this parameter may be able to be used to monitor changes in brain function associated with pharmacological treatment, and might also be able to predict treatment response.We performed a resting state fcMRI trial using a randomized, placebo-controlled, cross-over design to investigate mechanisms of action of milnacipran (MLN), a selective serotonin and norepinephrine reuptake inhibitor (SNRI), in fibromyalgia patients. Our aim was to identify functional connectivity patterns at baseline that would differentially predict treatment response to MLN as compared to placebo. Since preclinical studies of MLN suggest that this medication works by augmenting antinociceptive processes, we specifically investigated brain regions known to be involved in pain inhibition.15 fibromyalgia patients completed the study, consisting of 6 weeks of drug and placebo intake (order counterbalanced) with an interspersed 2 week wash out period. As a main finding we report that reductions in clinical pain scores during MLN were associated with decreased functional connectivity between pro-nociceptive regions and antinociceptive pain regions at baseline, specifically between the rostral part of the anterior cingulate cortex (ACC) and the insular cortex (IC), as well as between the periaqueductal gray (PAG) and the IC: patients with lower preexisting functional connectivity had the greatest reduction in clinical pain. This pattern was not observed for the placebo period. However a more robust placebo response was associated with lower baseline functional connectivity between the ACC and the dorsolateral prefrontal cortex.This study indicates that ACC–IC connectivity might play a role in the mechanism of action of MLN, and perhaps more importantly fcMRI might be a useful tool to predict pharmacological treatment response

Altered fMRI restingâ state connectivity in individuals with fibromyalgia on acute pain stimulation

BackgroundFibromyalgia is a chronic widespread pain condition, with patients commonly reporting other symptoms such as sleep difficulties, memory complaints and fatigue. The use of magnetic resonance imaging (MRI) in fibromyalgia has allowed for the detection of neural abnormalities, with alterations in brain activation elicited by experimental pain and alterations in resting state connectivity related to clinical pain.MethodsIn this study, we sought to monitor state changes in resting brain connectivity following experimental pressure pain in fibromyalgia patients and healthy controls. Twelve fibromyalgia patients and 15 healthy controls were studied by applying discrete pressure stimuli to the thumbnail bed during MRI. Restingâ state functional MRI scanning was performed before and immediately following experimental pressure pain. We investigated changes in functional connectivity to the thalamus and the insular cortex.ResultsAcute pressure pain increased insula connectivity to the anterior cingulate and the hippocampus. Additionally, we observed increased thalamic connectivity to the precuneus/posterior cingulate cortex, a known part of the default mode network, in patients but not in controls. This connectivity was correlated with changes in clinical pain.ConclusionsThese data reporting changes in restingâ state brain activity following a noxious stimulus suggest that the acute painful stimuli may contribute to the alteration of the neural signature of chronic pain.What does this study/add?In this study acute pain application shows an echo in functional connectivity and clinical pain changes in chronic pain.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/122449/1/ejp832_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/122449/2/ejp832.pd

Neurobiologic Features of Fibromyalgia Are Also Present Among Rheumatoid Arthritis Patients

Funding: The study recieved support from Pfizer. The funder had no role in study design, data collection, analysis, decision to publish or preparation of the manuscript. The content is solely the responsibility of the authors. Funding Information Pfizer Aptinyx Cerephex ACKNOWLEDGEMENTS: The authors wish to thank all of the patient volunteers. We also thank Mariella D’Allesandro for supporting recruitment and data collection.Peer reviewedPostprin

A novel paradigm to evaluate conditioned pain modulation in fibromyalgia

Application of noxious stimulation to one body area reduces pain sensitivity in a remote body area through activation of an endogenous pain-inhibitory network, a behavioral phenomenon referred to as conditioned pain modulation (CPM). The efficiency of CPM is predictive of a variety of health outcomes, while impaired CPM has been associated with various chronic pain conditions. Current methods used to assess CPM vary widely, and interest in CPM method development remains strong. Here, we evaluated a novel method for assessing CPM in healthy controls and fibromyalgia (FM) patients using thumb pressure as both a test and conditioning stimulus

Changes in Clinical Pain in Fibromyalgia Patients Correlate with Changes in Brain Activation in the Cingulate Cortex in a Response Inhibition Task

Objective The primary symptom of fibromyalgia is chronic, widespread pain; however, patients report additional symptoms including decreased concentration and memory. Performance‐based deficits are seen mainly in tests of working memory and executive functioning. It has been hypothesized that pain interferes with cognitive performance; however, the neural correlates of this interference are still a matter of debate. In a previous, cross‐sectional study, we reported that fibromyalgia patients (as compared with healthy controls) showed a decreased blood oxygen level dependent (BOLD) response related to response inhibition (in a simple G o/ N o‐ G o task) in the anterior/mid cingulate cortex, supplementary motor area, and right premotor cortex. Methods Here in this longitudinal study, neural activation elicited by response inhibition was assessed again in the same cohort of fibromyalgia patients and healthy controls using the same G o/ N o‐ G o paradigm. Results A decrease in percentage of body pain distribution was associated with an increase in BOLD signal in the anterior/mid cingulate cortex and the supplementary motor area, regions that have previously been shown to be “hyporeactive” in this cohort. Conclusions Our results suggest that the clinical distribution of pain is associated with the BOLD response elicited by a cognitive task. The cingulate cortex and the supplementary motor area are critically involved in both the pain system as well as the response inhibition network. We hypothesize that increases in the spatial distribution of pain might engage greater neural resources, thereby reducing their availability for other networks. Our data also point to the potential for, at least partial, reversibility of these changes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/108346/1/pme12460.pd

Alteration of grey matter volume is associated with pain and quality of life in children with sickle cell disease

Pain is the most common symptom experienced by patients with sickle cell disease (SCD) and is associated with poor quality of life. We investigated the association between grey matter volume (GMV) and the frequency of pain crises in the preceding 12 months and SCD-specific quality of life (QOL) assessed by the PedsQLTM SCD module in 38 pediatric patients with SCD. Using voxel-based morphometry methodology, high-resolution T1 structural scans were preprocessed using SPM and further analyzed in SPSS. The whole brain multiple regression analysis identified that perigenual anterior cingulate cortex (ACC) GMV was negatively associated with the frequency of pain crises (r = -0.656, P = 0.003). A two-group t-test analysis showed that the subgroup having pain crisis/crises in the past year also showed significantly lower GMV at left supratemporal gyrus than the group without any pain crisis (p=0.024). The further 21 pain-related regions of interest (ROI) analyses identified a negative correlation between pregenual ACC (r = -0.551, P = 0.001), subgenual ACC (r = -0.540, P = 0.001) and the frequency of pain crises. Additionally, the subgroup with poorer QOL displayed significantly reduced GMV in the parahippocampus (left: P = 0.047; right: P = 0.024). The correlations between the cerebral structural alterations and the accentuated pain experience and QOL suggests a possible role of central mechanisms in SCD pain

Brain Connectivity Patterns Dissociate Action of Specific Acupressure Treatments in Fatigued Breast Cancer Survivors

Persistent fatigue is a pernicious symptom in many cancer survivors. Existing treatments are limited or ineffective and often lack any underlying biologic rationale. Acupressure is emerging as a promising new intervention for persistent cancer-related fatigue; however, the underlying mechanisms of action are unknown. Our previous investigations suggested that fatigued breast cancer survivors have alterations in brain neurochemistry within the posterior insula and disturbed functional connectivity to the default mode network (DMN), as compared to non-fatigued breast cancer survivors. Here, we investigated if insula and DMN connectivity were modulated by self-administered acupressure by randomizing breast cancer survivors (n = 19) to two distinct treatments: relaxing acupressure or stimulating acupressure. All participants underwent proton magnetic resonance spectroscopy of the posterior insula and functional connectivity magnetic resonance imaging at baseline and immediately following 6 weeks of acupressure self-treatment. As compared to baseline measures, relaxing acupressure decreased posterior insula to dorsolateral prefrontal cortex connectivity, whereas stimulating acupressure enhanced this connectivity (p < 0.05 corrected). For relaxing but not stimulating acupressure, reduced connectivity was associated with sleep improvement. In addition, connectivity of the DMN to the superior colliculus was increased with relaxing acupressure and decreased with stimulating acupressure, whereas DMN connectivity to the bilateral pulvinar was increased with stimulating and decreased with relaxing acupressure (p < 0.05 corrected). These data suggest that self-administered acupressure at different acupoints has specificity in relation to their mechanisms of action in fatigued breast cancer survivors

A multi-modal MRI study of the central response to inflammation in rheumatoid arthritis

Special thanks to the patient community who participated in this research effort. Thanks to Mariella D’Allesandro for efforts towards recruitment.Peer reviewedPublisher PD

Altered Resting State Connectivity of the Insular Cortex in Individuals With Fibromyalgia

The insular (IC) and cingulate cortices (CC) are critically involved in pain perception. Previously we demonstrated that fibromyalgia (FM) patients have greater connectivity between the insula and Default Mode Network at rest, and that changes in the degree of this connectivity were associated with changes in the intensity of ongoing clinical pain. Here we more thoroughly evaluate the degree of resting state connectivity to multiple regions of the IC in individuals with FM and healthy controls (HC). We also investigated the relationship between connectivity, experimental pain and current clinical chronic pain. Functional connectivity was assessed using resting state functional magnetic resonance imaging in 18 FM patients and 18 age- and sex-matched HC using pre-defined seed regions in the anterior, middle and posterior IC. FM patients exhibited greater connectivity between: (1) right mid IC and right mid/posterior CC and right mid IC; (2) right posterior IC and the left CC; and (3) right anterior IC and left superior temporal gyrus. HCs displayed greater connectivity between: left anterior IC and the bilateral medial frontal gyrus/ACC; and left posterior IC and the right superior frontal gyrus. Within the FM group, greater connectivity between the IC and CC was associated with decreased pressure-pain thresholds. Perspective These data provide further support for altered resting-state connectivity between the IC and other brain regions known to participate in pain perception/modulation playing a pathogenic role in conditions such as FM. We speculate that altered IC connectivity is associated with the experience of chronic pain in individuals with fibromyalgia