| T O P I C R E V I E W |
| davebhoy |
Posted - 12/13/2005 : 12:15:53
did anyone else pick up on this - i only heard about it today on bbc radio 5 live an hour ago.
The Strain in Pain Lies Mainly in the Brain
Sean Mackey, M.D., Ph.D.
Pain serves highly useful functions such as to help us monitor the physical and emotional state of our body and to warn us to take action in the event of injury. People born without the ability to perceive pain often die at a very young age due to overwhelming infection caused by injuries they never felt. While this ability to perceive pain is beneficial to us in an acute setting, in chronic pain it serves no beneficial purpose. In the chronic pain setting, the site of original injury has often healed, however the patient is left with an unremitting pain condition that is often associated with depression, anxiety, decreased libido, altered appetite, and sleep disturbances. These chronic pain conditions have a huge impact on the individual, their family, and society as a whole. The impact on society in particular is only recently being appreciated.
We know that pain affects hundreds of millions of people worldwide and is a primary complaint resulting in physician visits and health care resource utilization [1]. The importance of pain as a major worldwide health care problem has been recognized by the World Health Organization [1], and the need for further research into pain mechanisms and control was recognized by the U.S. Congress in its declaration of the years 2001-2010 as the Decade of Pain Control and Research [2]. Pain contributes to the overall economic burden of disease through increased direct medical costs caused by additional health care resource utilization and high indirect costs through absenteeism and on-the-job loss of productivity [3]. Overall costs are projected at over $100 billion annually [4].
Research has demonstrated that our experience of pain is perceived within the human brain. The brain takes the electrochemical impulses generated from our body during injury and modulates or changes these impulses to ultimately become the conscious experience of pain. Some of the factors that modulate the pain experience include: attention/distraction, anxiety, fear, depression, and placebo. As we all know from our own experience, our perception of pain is not directly proportional to the extent of the injury or the intensity of the painful stimuli being applied. Each of these factors has a beneficial role in the setting of acute pain but can become maladaptive or harmful to the patient with chronic pain. For example, overwhelming fear of pain in a patient with chronic low-back pain with a stable spine and no neurological injury can lead to guarding and protective behaviors that result in deconditioning, back muscle shortening and spasm, and therefore more pain. This leads to a spiraling course of ever more increasing pain and disability.
Recently, through the use of neuroimaging tools such as functional magnetic resonance imaging (fMRI) and positron emission tomography (PET), researches have demonstrated within specific brain regions where pain is processed and perceived [5]. Each of these regions communicates with the others in a form of distributed parallel network. This results in multiple pathways within the brain that contribute to the pain experience. In the acute setting, this is beneficial in that if any one pathway is disrupted or injured, there are others to take over and contribute to the pain experience. However, in a chronic pain condition, particularly one that involves injury to nervous system, the patient is left feeling pain when there is no longer a direct stimulus. Take, for example, the patient who feels burning pain from a light breeze over their arm as a result of an injury many years ago. This patient’s injury is well healed, but the nervous system continues to misinterpret signals that should not be painful at all as being excruciating. We now understand that this patient’s pain is a result, in large part, through abnormal rewiring (i.e., central sensitization/neural plasticity) of the central nervous system (CNS) that perpetuate the pain despite the absence of a painful stimulus.
Our group is focused on utilizing state of the art neuroimaging tools to investigate the emotional and cognitive factors that influence pain as well as the neural plastic changes that occur in chronic pain. Details of current studies available here. We are directing these tools at both the spinal cord and brain to better understand our patient’s experience with the goal of developing new therapies to treat their condition. Recently, this technology has been extended to allow the subjects or patients to “see” their own brain activity in real time. They then use this information to learn to control their brain activation in a specific region associated with the processing and perception of pain (details here).
We are also actively involved in investigating: 1) applications of botulinum toxin in neuropathic pain, 2) the use of intravenous lidocaine as a diagnostic and therapeutic tool for neuropathic pain, 3) the effect of opiates on central sensitization (i.e., opiate induced hyperalgesia), and 4) assessing clinical chronic pain outcomes in our outpatient and inpatient setting.
These accomplishments would not directly impact patients unless there was a close connection with the clinic. This realization has led to the establishment of a close collaboration with the clinical enterprise at the Stanford Pain Management Center – California’s premier tertiary referral center for patients with chronic pain and the only academic center with a “chronic pain unit” in the western US. The center is staffed with outstanding physicians, psychologists, nurses, physical and occupational therapists who integrate the latest knowledge and Stanford research into their clinical practice.
The last decade has seen dramatic changes in the way we understand pain. Rather than viewing pain as simply a symptom of trauma, infection, inflammation, or surgery, we now see it as a discrete disease entity - one that fundamentally alters the entire nervous system. In a major recent advance, neuroimaging tools have allowed us to peer inside the human brain in ways once only dreamed about – unlocking mysteries of where pain is perceived and processed, how it affects the brain, and how it can act to change our thoughts and emotions. For the first time, we have the tools to effectively explore the impact of pain on the brain and can use this information to create the comprehensive interdisciplinary treatment needed to prevent or reverse these changes. Our ultimate goal is to lessen or stop our patient’s pain and restore and enhance their quality of life.
1. Gureje, O., et al., Persistent pain and well-being: a World Health Organization Study in Primary Care. Jama, 1998. 280(2): p. 147-51.
2. Public Law 106-386-OCT. 28, Victims of Trafficking and Violence Protection Act of 2000. Title VI, Section 1603, "Decade of pain control and research." 2000. Available at: http://209.190.246.239/tvpa.text.pdf.
3. Korzan, J.R., et al., In vivo magnetic resonance imaging of the human cervical spinal cord at 3 Tesla. J Magn Reson Imaging, 2002. 16(1): p. 21-7.
4. NIH Guide: New Directions in Pain Research: I. 1998., in Available at: http://grants2.nih.gov/grants/guide/pa-files/PA-98-102.html
5. Mackey S, Maeda F, Functional Imaging and the Neural Systems of Chronic Pain in Neurosurgery North American Clinics Neurosurgery Clinics of North America, July 2004, Vol. 15, No. 3; 269-288
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| 7 L A T E S T R E P L I E S (Newest First) |
| ralphyde |
Posted - 12/13/2005 : 19:46:38
quote:
For example, overwhelming fear of pain in a patient with chronic low-back pain with a stable spine and no neurological injury can lead to guarding and protective behaviors that result in deconditioning, back muscle shortening and spasm, and therefore more pain. This leads to a spiraling course of ever more increasing pain and disability.
And isn't this what Dr. Sarno says as well. "One has to confront TMS, fight it, or the symptoms will continue. Losing one's fear and resuming normal physical activity is possibly the most important part of the therapeutic process." HBP page 81.
Ralph |
| ralphyde |
Posted - 12/13/2005 : 19:40:14
quote:
To help jumpstart the process, we gave them suggestions as to how they could change their brain activity in the rACC. This included changing the focus of their attention on the pain, changing emotional value of the pain, as well as other similar strategies.
Doesn't this equate to Dr. Sarno's instruction to "Think psychological, not physical."? Basically, reprogramming your brain to change the focus.
Ralph |
| davebhoy |
Posted - 12/13/2005 : 16:28:09
sorry - i didnt know you could on this forum
there's two:
http://paincenter.stanford.edu/research/
http://paincenter.stanford.edu/research/rtfmristudy.html |
| n/a |
Posted - 12/13/2005 : 14:17:10
davebhoy
You did not provide the url for the article. Please post it. Sources are always important. Usually I can find this using google, but not this one. Thanks! |
| davebhoy |
Posted - 12/13/2005 : 13:17:37
for me its exciting because it suggests that my pain and fatigue can be controlled and also that if i address the reasons my brain is generating these then i can stop the impulses to create the pain completely |
| Becca |
Posted - 12/13/2005 : 13:07:54
Hi
That is ineresting research. I have come across other studies that hypothesize the same thing. The research makes me breathe a sigh of relief that the pain is not structural, but thinking that I could have an abnormal region in the brain makes me anxious as well. My TMS fear begins to obsess over my pain processing abnormality in my brain and I start to feel scared and helpless. So it really doesn't matter that my disc is herniated-waht really matters is my brain is weird! For now I think I am just going to concentrate on the things about the pain I can do something about-like my emotions and my reactions to the pain-R |
| davebhoy |
Posted - 12/13/2005 : 12:34:21
there's more. this is really interesting to me.
Learned Volitional Control Over Brain fMRI Activation and Pain
Control over brain activation and pain learned by using real-time functional MRI.
Proc Natl Acad Sci USA (2005) Download
deCharms, R. C., Maeda, F., Glover, G. H., Ludlow, D., Pauly, J. M., Soneji, D., Gabrieli, J. D., and Mackey, S. C.
We all consciously and unconsciously control our brain for every activity we initiate, every thought we have, and every emotion or sensation we experience. Until recently, it has been unclear as to what extent we can learn to control brain activity—more specifically, the activity of specific brain regions--and what impact that control would have on us. Well-defined regions of the brain are responsible for the perception of pain, and, in our pilot study, we sought to answer two questions:
Can people learn to control a specific region in the brain involved in pain perception known as the rostral anterior cingulate cortex (rACC)?
Does learned control of the rACC lead to changes in pain in both healthy subjects and in patients with chronic pain?
Functional magnetic resonance imaging (fMRI) is a tool that allows researchers to open windows into the brain and “see” brain activity. Until recently, fMRI data needed to be analyzed off-line with the results being unavailable until many hours after the subject was scanned. Through software developed by Dr. Christopher deCharms in collaboration with Stanford University, we are now able to analyze the imaging data in near real time and show a subject being scanned their own brain activity on a moment by moment basis.
Due to the magnitude and complexity of this study, we put together an interdisciplinary team of researchers to tackle the two questions above. This team included: Dr. Christopher deCharms (principle investigator for Omneuron, a San Francisco bay area startup), Dr. Fumiko Maeda (research associate), Dr. John Gabrieli (formerly professor of the Stanford Department of Psychology ; he is now at MIT), Dr. John Pauly (associate professor of electrical engineering), Dr. Gary Glover (professor of radiology and director, radiological sciences laboratory), Deepak Soneji and David Ludlow (research assistants in Dr. Mackey’s lab), and Dr. Sean Mackey (principle investigator who led the Stanford team).
We initially took 8 healthy subjects and used the real time fMRI information to help them learn to control their brain activations.
The initial part of the study involved exposing healthy subjects to a heat stimulus. First, outside of the scanner, we heated a small area of their skin using a computer-controlled Peltier device. We determined which temperature resulted in their experiencing a pain score of 7 out of 10 – where 0=no pain and 10=the worst pain imaginable. We then scanned their brain, while their skin was heated, to locate the regions of the brain responsible for their perception of pain. We found that an area of the brain – the rostral anterior cingulate cortex (rACC) – was reliably and strongly activated in these subjects. Resultantly, we focused on this area. We then placed subjects in the scanner and, while intermittently heating their skin, asked them to change their brain activity while watching a visual representation of this activity. The visuals used were both a moving line graph as well as a virtual flame that got brighter or dimmer as their brain activity increased or decreased, respectively.
Visual images subjects and patients visualized while changing their brain activity. PNAS, December 2005
To help jumpstart the process, we gave them suggestions as to how they could change their brain activity in the rACC. This included changing the focus of their attention on the pain, changing emotional value of the pain, as well as other similar strategies. Over several sessions, we monitored how well they learned to control the rACC and also had them rank their pain perception. We found a significant increase in the subject’s ability to control brain activation throughout training.
These results provided a positive answer to our first question as to whether subjects could learn to voluntarily control brain activity in a specific brain region.
As an answer to our second question, we found a significant increase in the ability of healthy subjects to control their pain with repeated training.
This was not a placebo response. Multiple control groups were run to insure that the rACC was truly modulating pain and that the immediate visual information of the rtfMRI information did indeed assist the subject in modulating their pain. We found that none of the control groups had an effect from training and no significant difference in pain. Overall, the healthy subjects using the real time information demonstrated an average of 23% enhancement in control over pain intensity and 38% enhancement in control over pain unpleasantness as compared with subjects in the control groups who did not receive the real time fMRI training.
Finally, we enrolled 8 patients with chronic intractable pain to test our original two questions. The study was conducted much like the healthy controls, except the patients used their own spontaneous/endogenous pain rather than an externally applied stimulus. In the small group of pain patients, they too demonstrated an ability to control their brain activity and subsequently their pain level. Overall, the pain patients noticed a 64% decrease in pain ratings on the McGill Pain Questionnaire (a survey form that measures both the sensory and emotional aspect of pain) and an average of 44% decrease on a visual analogue scale.
Taken together, these results suggest that, using real time fMRI, people can learn to strengthen the function of a specific region of the brain and, through that change, the regions associated with the perception of pain. It is similar to exercising muscles, but, in this case, the “muscle” is an area in the brain. We are currently conducting experiments to determine if other regions of the brain involved in pain processing can also be controlled.
A Message for Patients Suffering From Chronic Pain
We recognize that chronic pain hugely impacts not only patients but their families and friends as well. Often people seek out the newest research and treatments in the hopes of reducing their pain and suffering. While we are excited about the results of this study, we believe some cautions are in order in interpreting our results.
First, this was a small pilot study. Furthermore, while we studied 8 patients with chronic pain, they only made up a small part of our overall study design. The majority of the study involved healthy subjects experiencing an experimentally induced noxious stimulus (i.e., a non-injuring heat/pain stimulus). Consequently, although the results were statistically significant and the magnitude of the effects were clinically significant, these results must be replicated on a much larger scale.
Secondly, we did not actively monitor the duration of effect for the patients with chronic pain. Therefore, we have not shown that the results have any long-term effectiveness. We are currently studying that question.
Consequently, this study should not be interpreted to suggest that real time fMRI is in any way to be thought of as a current treatment for chronic pain. There is much science and work to be done to demonstrate real clinical benefit. Although optimistic about the future, the authors advise that patients not get their hopes up that this method would cure their chronic pain. Our results do not give any indication to support that.
We are currently enrolling subjects in a long term study and are looking for qualified candidates. To determine if you are an appropriate candidate and for detailed information about the study, please click here (.doc / .rtf). If you are interested, please contact our research assistant, Axel Lucca, at 650-724-8783. |
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