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12 Articles in Volume 11, Issue #1
Simultaneous Use of Stimulants 
and Opioids
Therapy for Management of Childbirth Perineal Tears and Post-Partum Pain
Measuring Clinical Outcomes of Chronic Pain Patients
Real-Time Functional Magnetic Resonance Imaging in Pain Management
A Non-Surgical Treatment for Carpal Tunnel Syndrome
Fibromyalgia, Chronic Widespread Pain, and the Fallacy of Pain from Nowhere
Sonoanatomy and Injection Technique of the Iliolumbar Ligament
Back Surgery That Does Not Relieve Pain
The Immune System and Headache
Diversity in Pharmacologic Treatment of Pain
Memantine for Migraine and Tension-Type Headache Prophylaxis
Pain Management in Inflammatory Arthritis

Real-Time Functional Magnetic Resonance Imaging in Pain Management

Severe chronic pain patients are able to use real-time fMRI to observe the functioning of their own brain’s pain system and, using this neurofeedback, control activation of specific brain regions involved in pain perception/regulation to reduce pain.

Chronic pain is debilitating to the patient and puts an enormous strain on the healthcare delivery system. It is the primary complaint resulting in physician visits and the use of healthcare resources. 1 Chronic pain costs the United States about $150 billion a year. 2 The purpose of this study is to review the current literature on the use of functional Magnetic Resonance Imaging (fMRI) in pain management and to suggest a range of potential future applications. These include alternative therapy for chronic pain sufferers, pharmacological research in the development and testing of new analgesics, real-time feedback for osteopathic manipulative techniques to ease pain, the creation of new objective pain scales, and brain mapping of specific pain types. These potential applications could have a major impact on improving the quality of life and functional ability of chronic pain patients, who often have great difficulty controlling pain that is often unresponsive to traditional treatment. They also could help to reduce the enormous burden that chronic pain puts on the healthcare delivery system.


Functional Magnetic Resonance Imaging

Magnetic resonance imaging—traditionally used for anatomical imaging—is now widely used to observe brain structures and functions. Recent advances in computing power and software make it possible for the patient and doctor to view the subject’s brain as it functions in nearly real time. By observing the functioning of their own brain’s pain system, patients have been trained to reduce the level of severe, chronic pain significantly. 3 This could offer relief for the estimated 50 million to 80 million Americans living with chronic pain. 


Functional magnetic resonance imaging, or fMRI, could be the most suitable candidate for routine clinical use in the evaluation of pain. 4 Long-term changes in brain structures have been linked to the exaggeraged brain activity of chronic pain patients. Researchers have found that individuals with chronic back pain sustained alterations in the functional connectivity of the cortical regions. 5 These areas of the brain are related to emotions. The non-stop firing of neurons in the frontal part of the cortex changes the neurons’ connections and can lead to depression, anxiety, sleep disturbances and cognitive dysfunction.


Functional MRI shows the amount of blood flow to specific brain regions and so provides an indirect indication of brain activity. Chronic pain disrupts the natural resting state of the brain, known as the default mode network (DMN). Patients with chronic back pain show less neocortical gray matter volume than control patients, but this gray matter atrophy can be reversed. 6 The brain matter decrease is the consequence and not the cause of pain.


According to researchers at University College London, functional MRI can be used as a new paradigm in cognitive neuroscience to study brain plasticity and the functional relevance of brain areas. 7 Online analysis of single-subject data provides immediate quality assurance. It also provides functional localizers guiding experiments or surgical interventions. Functional MRI allows for brain-computer interfaces (BCI), with a high spatial and temporal resolution and whole brain coverage. 


Honda Research Institute Japan and the Advanced Telecommunications Research Institute International have created the first brain-machine interface that enables control of a robot by thought alone. The technology uses a functional MRI scanner and achieved the first success in the world to control a robot hand by decoding brain activities without electrode array implants or special training of the user. The technology is described in a corporate news release issued by Honda in 2009. 8

Researchers at University Hospital Basel in Switzerland found that real-time functional MRI feedback training may improve chronic tinnitis, a more or less constant ringing in the ears. 9 The excess auditory activation significantly decreased after fMRI neurofeedback. 


According to Columbia University’s Program for Imaging and Cognitive Sciences (PICS), the number of medical research centers with functional MRI capabilities continues to grow. The technology provides the ability to observe the brain structures and also to discern which structures participate in specific functions. PICS’ website 10 states that fMRI provides high-resolution images without the need to inject radioactive isotopes. It can be used to noninvasively map changes in brain hemodynamics that correspond to mental operations. Columbia University says its pilot studies of patients with chronic sympathetically-maintained pain affecting one extremity suggest a wide range of other approaches using fMRI to investigate cortical representations of specific pain types and, therefore, new specific therapy options. 


Self-Regulation Using fMRI


Much of the early research in the use of fMRI to train patients in pain management was done at Stanford University and is being continued in conjunction with a private company, Omneuron, Inc. at Menlo Park, California. In a few brief sessions, each lasting 13 minutes, patients can learn to control activity in different parts of their brain and change their sensitivity to painful stimuli. Individuals can learn to exert deliberate, voluntary control over localized brain activation by using real-time fMRI as feedback. 3

Richard Chapman, director of the Pain Research Center at the University of Utah in Salt Lake City, says it should eventually be possible to identify patterns of brain activity involved in perpetuating chronic pain and then to introduce interventions that we know from published evidence can block or compete with those patterns. 2 Researchers at Northwestern University in Chicago found that a stimulus which healthy human subjects perceive as a reward might be processed quite differently in the brains of chronic pain sufferers. 11 The findings point to a possible dysfunctional associative learning process in chronic pain patients. 


Mindfulness meditation has been used with limited success in the treatment of chronic pain. 12 Control over the endogenous pain modulation system could enable a unique mechanism for control of pain. Interestingly, patients who learned such control using real-time functional MRI are able to do so only by observing the functioning of the brain’s pain system. 3 Conventional biofeedback using autonomic measures was not successful. Patients who learned to control activation in the rostral anterior cingulate reported decreases in the ongoing level of chronic pain in pilot studies at Stanford University. Patients watch from inside the MRI scanner using virtual reality eyeglasses. A computer translates the MRI signals into three small, animated fires, representing the activity level of the cingulate and the right and left insula, which are regions involved in processing pain. 2 Researchers at Eberhard-Karls-University of Tübingen in Germany found that participants were able to successfully regulate the signal strength in the right anterior insular cortex within three sessions of four minutes each. 13 Their work shows that self-regulation of local brain activity with fMRI is possible.


Researchers in the UK and Canada used fMRI to reveal the neural substrates of arm transport and grip formation in reach-to-grab actions in humans such as reaching out to pick up a coffee cup. 14 They identified the superior parieto-occipital cortex and the rostral superior parieto lobule as the neural substrates of the transport component. They found specialization for the grip component in the bilateral anterior intraparietal sulcus and left ventral premotor cortex. They also found an integration of the two components in the dorsal premotor cortex and supplementary motor areas.


fMRI As a Diagnostic Tool


Current methods of diagnosis of autism spectrum disorder in adults can be lengthy and expensive. Experts at Kings College London identified subtle but crucial signs of autism that are only detectable by computer. 15 The researchers detected autism using MRI with more than 90% accuracy. They suggested that the findings might result in a widely available brain scan to test for autism. 


Recent advances in brain-imaging techniques could lead to better diagnosis and perhaps better drug treatments of chronic pain. Researchers at Massachusetts General Hospital and Children’s Hospital Boston cite possible applications of brain imaging to develop a pain phenotype, or observable characteristics, that could aid in diagnosis and treatment choices of chronic pain conditions. 16 Chronic pain not only affects the somatosensory system, but it is also a condition in which emotional, cognitive and modulatory areas of the brain are affected, in addition to degenerative processes. It has a widespread impact on overall brain function.


Previous studies on the brain basis of chronic pain have concentrated on abnormal activation sites and strengths following external stimulation. Researchers in Finland focused on the resting-state fluctuations and functional connectivity of the affective pain-processing areas. 17 They found regularly occurring blood-oxygen-level-dependent (BOLD) fluctuations that were significantly faster in chronic pain patients. They said this could be explained by decreased functional connectivity of the affective-emotional pain matrix. These findings emphasize the importance of closer scrutiny of time courses of brain activity and the need for information about the influence of various drugs on the BOLD fluctuations. 


Researchers led by S. Stevens Negus of Harvard Medical School found that patterns of fMRI activation not only serve as potential physiological correlates of pain or analgesia but also describe neural circuits that may underlie these sensations and their associated patterns of behavior. 18 Activation across the whole brain associated with the delivery of analgesic drugs may thus be assessed noninvasively. 


Medical personnel rely on self-reporting for pain assessment. However, infants cannot use words to explain what they are feeling. Therefore, fMRI has potential applications in neonatal pain management—particularly for premature babies. 19 It could also be useful in adjusting the dosage of analgesics in unconscious patients.


Conclusion

This review of the literature suggests a range of potential applications of real-time fMRI including alternative therapy for chronic pain sufferers, pharmacological research in the development and testing of new analgesics, the creation of new objective pain scales, and brain mapping of specific pain types. In addition, fMRI could be used to provide real-time feedback of osteopathic manipulative techniques to alleviate pain. This could provide an objective measurement of changes in brain activity during osteopathic manipulation to discern which treatments are most effective. 


These potential applications could have a major impact on improving the quality of life and functional ability of chronic pain patients, who often have great difficulty controlling pain that is unresponsive to traditional treatment. Advances in fMRI technology that enable us to see the brain function in nearly real time suggest a wealth of new approaches to pain management.

Last updated on: March 7, 2011
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