Pain in the United States is common and costly, with over 1 in 3 individuals being afflicted causing an economic burden approaching $600 billion annually. This problem results from our lack of understanding the underlying mechanisms of most forms of chronic pain which in turn has hampered our ability to develop new effective treatments. Fibromyalgia (FM) is a common chronic pain condition whose pathology is largely unknown. Existing research suggests that the brain may play a significant role in pain expression in these individuals. Although untested, an imbalance in excitatory and inhibitory brain activity may lead to an unstable neural network sensitized to external stimuli and this may lead to pain in FM. Hypersensitive and unstable networks have been observed in various physical and biological systems, and in such networks, small perturbations can give rise to explosive and global propagation of activity over the system. One underlying mechanism of hypersensitive systems, called explosive synchronization (ES), has been introduced and actively studied over the past decade. ES is a phenomenon wherein small increases in stimulation strength applied to a network, can lead to an abrupt state transition through global network synchronization. Here we hypothesize that ES may be an underlying mechanism of the hypersensitivity of the FM brain, and a targeted approach with non-invasive brain stimulation may reduce conditions or ES and subsequent pain in some of these patients. Our pilot electroencephalogram (EEG) data showed that the FM brain displays network configurations primed for ES. Individuals with more clinical pain had increased ES conditions within their brain networks. Furthermore, when these same patients experienced an increase in pain following an experimental pressure pain stimulus applied to the thumb, they exhibited a concomitant increase in ES. Understanding how the development of hypersensitivity within the brain can lead to chronic pain is an unknown in the medical field and is the major theme of this proposal. We posit that finding the underlying mechanism of hypersensitivity in the FM brain could lead to a more fundamental understanding of the central nervous system sensitization seen in this pain state (and potentially others), and targeting this phenomenon might be an effective new treatment strategy. To achieve this goal, we propose three aims based on interdisciplinary approaches of neuroscience, physics, medicine, and mathematics:
Aim 1. Demonstrate that individuals with FM, as compared to pain free controls, display brain characteristics of ES as assessed with EEG.
Aim 2. Computationally model the underlying mechanism(s) of the hypersensitive FM brain and identify key target regions that might reduce brain hypersensitivity.
Aim 3. Test the ability of high definition transcranial direct current stimulation (HD-tDCS) at discrete network regions to reduce conditions of ES within the brain.
In the US, chronic pain and opioid over-use are reaching epidemic proportions where one in three citizens experiences some degree of pain and over 33,000 opioid related deaths occur annually. High definition transcranial direct current stimulation (HD-tDCS) is a novel, safe, non-invasive, non-opioid, brain treatment that reduces the severity of some types of chronic pain. In this study we will investigate the ability of HD-tDCS to reduce unstable brain network behavior that may drive pain in fibromyalgia, and likely other chronic pain conditions, thus leading to much needed novel treatment strategies for pain.
