An Examination of Brain Network Organization and the Analgesic Mechanisms of a Non-Pharmacological Treatment in Chronic Centralized Pain

chronic pain;brain network;functional magnetic resonance imaging (fMRI);glutamate;fibromyalgia;transcranial direct current stimulation (tDCS);Neurosciences;Health Sciences;Neuroscience

Kaplan, ChelseaSeidler, Rachael D ;

University of Michigan

关键词: chronic pain;    brain network;    functional magnetic resonance imaging (fMRI);    glutamate;    fibromyalgia;    transcranial direct current stimulation (tDCS);    Neurosciences;    Health Sciences;    Neuroscience;   

Others  :  https://deepblue.lib.umich.edu/bitstream/handle/2027.42/143930/chelsmar_1.pdf?sequence=1&isAllowed=y

瑞士|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 摘 要 】

Chronic pain is a global public health challenge, affecting nearly one third of adults worldwide. Current treatments are inadequate, especially since some of the mainstay therapies (e.g. opioids, NSAIDs) are often ineffective and/or associated with significant toxicity. The solution to these problems requires an improved understanding of chronic pain pathology, particularly the role that the brain plays in causing or amplifying pain perception, and how analgesic intervention might target these brain-based mechanisms. This dissertation aims to identify brain network alterations in fibromyalgia (FM), a common and canonical chronic pain condition with presumed CNS pathology, and determine how non-invasive brain stimulation may target aberrant brain network connectivity to promote analgesia. Across a wide range of diverse neurological disorders, hubs (i.e. highly connected brain regions) appear to be disrupted and the character of this disruption can yield insights into the pathophysiology of these disorders.In Chapter 2, we describe the application of a brain network based approach to examine hub topology in FM patients compared to healthy volunteers. We identified significant disruptions in hub rank order in FM patients. In FM, but not controls, the anterior insula was a hub with significantly higher inter-modular connectivity and membership in the rich club (a functional backbone of connectivity formed by highly interconnected hubs). Among FM patients, rich club membership varied with the intensity of clinical pain: the posterior insula, primary somatosensory and motor cortices belonged to the rich club only in FM patients with the highest pain.Further, we found that the eigenvector centrality (a measure of how connected a brain region is to other highly connected regions) of the posterior insula positively correlated with clinical pain, and mediated the relationship between levels of glutamate + glutamine within this structure and the patient’s subjective clinical pain report.Together, these findings demonstrate an altered hub topology in FM and are the first to suggest that disruptions in the excitatory tone within the insula could alter the strength of the insula as a hub and subsequently lead to increased clinical pain. Transcranial direct current stimulation (tDCS) has emerged as an attractive noninvasive treatment for pain, given its ability to target specific cortical regions with relatively few side effects.Motor cortex (M1) tDCS relieves pain in FM, but the analgesic mechanism remains unknown. In Chapter 3, we measured changes in resting state functional connectivity after sham and real M1 tDCS in twelve FM patients and examined if these changes were related to subsequent analgesia.M1 tDCS (compared to sham) reduced pro-nociceptive functional connectivity, specifically between the motor and sensory nuclei of the thalamus and multiple cortical regions, including primary motor and somatosensory areas. Interestingly, decreased connectivity between the thalamus and posterior insula, M1 and somatosensory cortices correlated with reductions in clinical pain after both sham and active treatment. These results suggest that while there may be a placebo response common to both sham and real tDCS, repetitive M1 tDCS causes distinct changes in functional connectivity that last beyond the stimulation period and may produce analgesia by inhibiting pro-nociceptive thalamic connectivity.This research offers new insight into the neurobiology of chronic centralized pain conditions and contributes to the understanding of how non-invasive brain stimulation causes analgesia. This knowledge could lead to more informed stimulation sites and personalized treatment based on network connectivity in each individual patient.