David Baxter PhD
Late Founder
Next Generation of Fibromyalgia Research
Daniel J. Clauw, MD, Professor, Anesthesiology and Medicine (Rheumatology), University of Michigan
Psychiatry Weekly, Volume 3, Issue 38
December 1, 2008
This interview was conducted on October 21, 2008 by Lonnie Stoltzfoos
Fibromyalgia, once viewed with skepticism by many in the medical field, is increasingly recognized as an organic disorder characterized by a heightened sensitivity to pain and other sensory stimuli, rather than as a somatization syndrome. According to Dr. Daniel J. Clauw, this shift in thinking can be attributed directly to the spate of new data that indicate a strong genetic component in fibromyalgia, and objective differences identifiable in functional neuroimaging studies.
?More and more physicians are now seeing the scientific studies that have been performed on fibromyalgia over the past decade?brain imaging studies, genetic studies, cerebrospinal neurotransmitter studies?that show a strong biological underpinning to this entire spectrum of illness,? says Dr. Clauw. ?When physicians see those data and see that there are drugs that are easy to prescribe that actually can be of benefit to patients, then they are typically much more accepting of the fibromyalgia construct that they once were.?
According to current data, ~50% of the risk for fibromyalgia is genetic; environmental factors account for the remaining risk.
?An explosion of science in the pain field has shown us that, for example, if someone has fibromyalgia, the risk of one of their first-degree relatives having fibromyalgia is 8-fold greater,? explains Dr. Clauw. ?We have learned only over the past 5?10 years how genetic pain transmission is, and that specific polymorphisms are strongly involved in human pain sensitivity.?
Some studies show, for example, that there are high levels of neurotransmitters in the spinal fluid of fibromyalgia patients. These neurotransmitters, which are believed to increase pain transmission, can include substance P, glutamate, and nerve growth factor. Also, there is evidence to suggest that other neurotransmitters that have a tendency to inhibit pain, such as serotonin and norepinephrine, are low in fibromyalgia patients.
?The current notion is that, in this spectrum of illness, there is an increased gain, or increased volume, of pain transmission, which leads to a state of hyperalgesia or allodynia,? says Dr. Clauw. ?This is due to either high levels of neurotransmitters that are excitatory in pain transmission and/or low levels of neurotransmitters that are inhibitory and decreased pain transmission.?
In a 2008 investigation, Clauw, Harris, and colleagues discovered, using proton spectroscopy, that glutamate levels are higher in the insula of fibromyalgia patients, and that the levels of glutamate seemed to correlate with the degree of symptoms.
?This is a fascinating finding, because the insula is the region of the brain that integrates all sensory information,? explains Dr. Clauw. ?Hyperactivity of the insula has been found on all the brain imaging studies done in fibromyalgia and in most of the brain imaging studies done in irritable bowel syndrome, temporomandibular joint disorder, and other symptoms that track with fibromyalgia. And so hyperactivity of the insula that is partly due to, or related to, high levels of glutamate in the insula would cause individuals to have augmented pain sensitivity, as well as more sensitivity to a number of sensory stimuli.?
Treatment Outlook
There is now a gap between the treatment of fibromyalgia and the increasingly advanced etiological findings, leaving room for more advanced treatments to catch up. Cognitive behavioral therapy, exercise, certain antidepressants, and some anticonsulvants, are among the more common treatments. Although these treatments often work reasonably well, choosing which treatment?behavioral or pharmacologic?to apply to any given patient is still a process of trial and error.
Dr. Clauw says, however, that ?most of us in the pain field are hopeful, or almost certain, that pain is so genetic that in 3?5 years we will have gene chips with 30?40 different genes that control human pain sensitivity on it. This could help us identify patients who, for example, have hyperalgesia because of a COMT polymorphism?someone who might respond to a drug that modulates norepinephrine. In contrast, the next patient may have developed hyperalgesia/allodynia because of a lack of the enzyme that breaks down substance P, and they would be more likely to benefit from a drug that inhibits the release of substance P. For now, all we can really do in conditions like fibromyalgia to subset individuals is identify the people with or without psychological comorbidities and to use commensurate behavioral or pharmacologic therapies.?
Data from the mid to late nineties suggested that, for the average person, it took 5?7 years from when they first developed symptoms until being diagnosed with fibromyalgia, during which time they saw 6?8 different doctors. It appears that more fibromyalgia cases are being identified earlier than before, which provides a more encouraging outlook for prospective treatment outcomes.
Conclusion
?Some people worry, appropriately, whether we could be ?medicalizing? the mild aches and pains of everyday life,? says Dr. Clauw. ?That is a theoretical possibility, but the current data do not support it. There have been three different studies looking at what happens to someone after they?re given the label of fibromyalgia, and in all cases healthcare utilization actually goes down, largely because they are no longer going from sub-specialist to sub-specialist and getting unhelpful additional diagnostic tests.
?My own personal belief is that a lot of the functional disability that often accompanies fibromyalgia can be prevented with earlier diagnosis and treatment,? continues Dr. Clauw. ?If we don?t treat symptoms early enough, patients can develop a lot of functional disability, which can have severely detrimental effects on their lives for a long time, destroying many aspects of their lives and making rehabilitation very difficult. I think with earlier interventions with drug and non-drug therapies it will be far easier to prevent individuals from becoming a tertiary care pain patient than to treat them once this occurs.?
Daniel J. Clauw, MD, Professor, Anesthesiology and Medicine (Rheumatology), University of Michigan
Psychiatry Weekly, Volume 3, Issue 38
December 1, 2008
This interview was conducted on October 21, 2008 by Lonnie Stoltzfoos
Fibromyalgia, once viewed with skepticism by many in the medical field, is increasingly recognized as an organic disorder characterized by a heightened sensitivity to pain and other sensory stimuli, rather than as a somatization syndrome. According to Dr. Daniel J. Clauw, this shift in thinking can be attributed directly to the spate of new data that indicate a strong genetic component in fibromyalgia, and objective differences identifiable in functional neuroimaging studies.
?More and more physicians are now seeing the scientific studies that have been performed on fibromyalgia over the past decade?brain imaging studies, genetic studies, cerebrospinal neurotransmitter studies?that show a strong biological underpinning to this entire spectrum of illness,? says Dr. Clauw. ?When physicians see those data and see that there are drugs that are easy to prescribe that actually can be of benefit to patients, then they are typically much more accepting of the fibromyalgia construct that they once were.?
According to current data, ~50% of the risk for fibromyalgia is genetic; environmental factors account for the remaining risk.
?An explosion of science in the pain field has shown us that, for example, if someone has fibromyalgia, the risk of one of their first-degree relatives having fibromyalgia is 8-fold greater,? explains Dr. Clauw. ?We have learned only over the past 5?10 years how genetic pain transmission is, and that specific polymorphisms are strongly involved in human pain sensitivity.?
Some studies show, for example, that there are high levels of neurotransmitters in the spinal fluid of fibromyalgia patients. These neurotransmitters, which are believed to increase pain transmission, can include substance P, glutamate, and nerve growth factor. Also, there is evidence to suggest that other neurotransmitters that have a tendency to inhibit pain, such as serotonin and norepinephrine, are low in fibromyalgia patients.
?The current notion is that, in this spectrum of illness, there is an increased gain, or increased volume, of pain transmission, which leads to a state of hyperalgesia or allodynia,? says Dr. Clauw. ?This is due to either high levels of neurotransmitters that are excitatory in pain transmission and/or low levels of neurotransmitters that are inhibitory and decreased pain transmission.?
In a 2008 investigation, Clauw, Harris, and colleagues discovered, using proton spectroscopy, that glutamate levels are higher in the insula of fibromyalgia patients, and that the levels of glutamate seemed to correlate with the degree of symptoms.
?This is a fascinating finding, because the insula is the region of the brain that integrates all sensory information,? explains Dr. Clauw. ?Hyperactivity of the insula has been found on all the brain imaging studies done in fibromyalgia and in most of the brain imaging studies done in irritable bowel syndrome, temporomandibular joint disorder, and other symptoms that track with fibromyalgia. And so hyperactivity of the insula that is partly due to, or related to, high levels of glutamate in the insula would cause individuals to have augmented pain sensitivity, as well as more sensitivity to a number of sensory stimuli.?
Treatment Outlook
There is now a gap between the treatment of fibromyalgia and the increasingly advanced etiological findings, leaving room for more advanced treatments to catch up. Cognitive behavioral therapy, exercise, certain antidepressants, and some anticonsulvants, are among the more common treatments. Although these treatments often work reasonably well, choosing which treatment?behavioral or pharmacologic?to apply to any given patient is still a process of trial and error.
Dr. Clauw says, however, that ?most of us in the pain field are hopeful, or almost certain, that pain is so genetic that in 3?5 years we will have gene chips with 30?40 different genes that control human pain sensitivity on it. This could help us identify patients who, for example, have hyperalgesia because of a COMT polymorphism?someone who might respond to a drug that modulates norepinephrine. In contrast, the next patient may have developed hyperalgesia/allodynia because of a lack of the enzyme that breaks down substance P, and they would be more likely to benefit from a drug that inhibits the release of substance P. For now, all we can really do in conditions like fibromyalgia to subset individuals is identify the people with or without psychological comorbidities and to use commensurate behavioral or pharmacologic therapies.?
Data from the mid to late nineties suggested that, for the average person, it took 5?7 years from when they first developed symptoms until being diagnosed with fibromyalgia, during which time they saw 6?8 different doctors. It appears that more fibromyalgia cases are being identified earlier than before, which provides a more encouraging outlook for prospective treatment outcomes.
Conclusion
?Some people worry, appropriately, whether we could be ?medicalizing? the mild aches and pains of everyday life,? says Dr. Clauw. ?That is a theoretical possibility, but the current data do not support it. There have been three different studies looking at what happens to someone after they?re given the label of fibromyalgia, and in all cases healthcare utilization actually goes down, largely because they are no longer going from sub-specialist to sub-specialist and getting unhelpful additional diagnostic tests.
?My own personal belief is that a lot of the functional disability that often accompanies fibromyalgia can be prevented with earlier diagnosis and treatment,? continues Dr. Clauw. ?If we don?t treat symptoms early enough, patients can develop a lot of functional disability, which can have severely detrimental effects on their lives for a long time, destroying many aspects of their lives and making rehabilitation very difficult. I think with earlier interventions with drug and non-drug therapies it will be far easier to prevent individuals from becoming a tertiary care pain patient than to treat them once this occurs.?
