Psychological Factors

Relationship between Neurilogical Factors and Psychological, Cognitive, and Behavioural Factors in Fibromyalgia.

Extract from a talk to rheumatologists by Dr Daniel J Clauw, MD.

One of the most controversial questions in this illness is what is the relationship between physiologic or neurobiologic factors and psychologic and behavioral factors. If you do research in this area, you quickly realize that the old dualist notion of organic versus functional illnesses needs to be abandoned, because everything that is psychologic or behavioral likely has neurobiologic and physiologic underpinnings, and psychologic and behavioral factors play significant roles in even the most biologic of illnesses. In fact, I think that one of the big tragedies regarding this spectrum of illness is that 30 or so years ago, fibromyalgia had equally poor credibility as a real disease with mental health disorders such as bipolar disease, major depression, and schizophrenia. But now these latter conditions are more credible than fibromyalgia, in large part because scientific studies have shown that there are strong biologic underpinnings to these illnesses. The research showing strong biologic underpinnings is equally strong in this spectrum of illness, but most physicians and the lay public are not yet aware of these findings. This will likely change rapidly in the next few years as new drugs are approved specifically for fibromyalgia, and the companies marketing these drugs will do a thorough job of educating both physicians and patients about these conditions. Until then, though, these patients are shunned and inappropriately treated in our current health care systems. Everyone is averting their eyes and acting like they're not part of the problem here. But we are. Rheumatologists don't want fibromyalgia. Gastroenterologists don't want IBS. None of the subspecialties want this. So there never has been an advocacy campaign like the psychiatrists and other mental health professionals mounted to legitimize psychiatric conditions.

Having said that I'm not a dualist, it can actually be very helpful when you're sitting across the examination room from a fibromyalgia patient, to be a bit dualistic, and ask yourself how much social, cognitive, behavioral, and psychological factors are playing a role in symptom expression. Not all fibromyalgia patients are the same. Some of them respond very well to a little bit of a tricyclic drug and a little bit of education, and they never come back because they do fine. Others don't get better no matter what we do. We did a study published in Arthritis & Rheumatism a couple of years ago where we tried to develop subgroups based on 3 different domains. One domain was neurobiological; that was how tender people were using these more sophisticated measures of pressure pain threshold. One domain was whether they were depressed or anxious. And then the third domain was cognition, how they think about their pain. There are 2 particular cognitive patterns that are known to be very negative in pain. One is catastrophizing, which means that people have a very negative, pessimistic view of what their pain is and what it's doing to them. The other is an external locus of control, which basically means that people feel as though they can't do anything about their pain, so they can't control their pain. This study that I referred to earlier looked at 97 patients that we had been seeing at Georgetown, and 50 of them fell into the group we refer to as primary-care fibromyalgia patients.11 These people all met ACR criteria for fibromyalgia, but this subgroup was not depressed, they weren't anxious, they weren't very tender. They had enough tender points to meet the ACR criteria, but they weren't very tender using more sophisticated measures of pressure pain threshold. And they didn't have any negative cognitive factors, in that they didn't catastrophize, and had a moderate sense that they could control their pain. So in these people, they didn't have psychologic factors that seemed to be driving their pain to be worse, yet they had fibromyalgia. These people likely do fairly well with the kinds of treatments that we now recommend giving people with fibromyalgia.

At the beginning of this talk, I usually ask people to remember a fibromyalgia patient, and when I get to this point of the talk, I say that that fibromyalgia patient that you remembered is in the second subgroup, that we refer to as tertiary care fibromyalgia patients. You, as a rheumatologist, are not well equipped to make this person better, because what's going on in their spinal cord and brain with respect to their pain processing is the least of their problems. In addition to being tender, they're depressed, anxious, they catastrophize, they have no sense they can control their pain. These are people that have very prominent psychological factors above and beyond what might be contributing to their tenderness. These are people that even the best multidisciplinary pain programs have difficulty making better, and they certainly are not going to get better by just giving them a drug that somehow modifies pain processing in the brain or spinal cord. It is naive to think that you're going to make this kind of person better by just giving them a drug, because superimposed on a central nervous system problem with pain processing, these individuals have had significant social, cognitive, behavioral, and psychologic consequences of years or decades of untreated pain and other somatic symptoms.

The third subgroup that we identified in this study was very interesting. This group was the most tender of the three, suggesting that there was something quite wrong with how they processed pain. But despite this, these people were not anxious, they weren't depressed, they weren't catastrophizing. They actually had a moderate sense they could do something about their pain. These are individuals in whom psychologic resiliency seems to be buffering them against the neurobiological effects of fibromyalgia. In spite of what's going on in their brain and their spinal cord that is increasing their volume control setting and moving them to the right side of the bell-shaped curve, somehow they're coping and they're dealing with this condition much better than the other 2 groups. Several groups are now exploring whether it is possible to instill this resiliency into chronic pain patients. This is a relatively new thing in psychology; psychologists until recently focused on psychopathology, on anxiety, on depression, on the bad things that happen in psychology.

I've noted several times that the fundamental problem with this spectrum of illness is in pain processing or sensory processing. One of the things that you should be aware of is that in fibromyalgia, as well as in IBS and most of the other conditions in this spectrum, it is not just painful stimuli to which these people are more sensitive. They are more sensitive to auditory loudness, bright lights, odours, and other sensory stimuli. In fact, accounts for the overlap between multiple chemical sensitivity (which is a misnomer) and fibromyalgia. Thus, it is appearing that this is not multiple chemical sensitivity; it is really multiple sensory sensitivity. People are just sensitive to a lot of different sensory stimuli. Back to talking about the sensation of pain, there are a number of different ways that people can theoretically move to the right end of this bell-shaped curve, and have an increased volume control in pain processing. Some of these mechanisms by which this occur involve peripheral nerves, whereas others are central mechanisms, involving the brain or spinal cord. One of the primary problems in fibromyalgia patients appears to be not that there is too much input coming from the pressure nociceptors or the thermal nociceptors, but rather that there is inadequate filtering of that activity, perhaps because of decreased activity of descending antinociceptive pathways.12,13 These pathways begin in the brain and brainstem and descend into the dorsal horn of the spinal cord and are normally responsible for inhibiting the upward transmission of pain. It appears that these pathways are not working properly in individuals with fibromyalgia. So a lot of nociceptive information that may be filtered out in normal individuals may not be filtered out in fibromyalgia patients.

In addition to these studies that have used experimental pain testing to elucidate some of the underlying mechanisms in fibromyalgia, one of the other tools that you can use to look at pain processing in conditions like fibromyalgia is functional imaging. Our group, led by Rick Gracely, has performed many functional imaging studies in fibromyalgia. One of the big advantages of using functional brain imaging is that, because of animal and then later human studies that have been going on for the past 3 decades, we now know the regions of the brain that are involved in pain processing. Thus, we can give people painful stimuli under different conditions and image the neuronal activation patterns to infer how pain processing is different in fibromyalgia patients and controls. The areas of the brain that are involved in the sensory dimension of pain, which is basically where the pain located, and how much it hurts, are the primary and secondary somatosensory cortex and thalamus. There are other regions of the brain that are more involved in the affective dimension of pain or the emotional valance of pain, or in how they think about their pain, and these include regions such as the insula, anterior cingulated, amygdale, and prefrontal cortex. In the first study that used functional MRI to study pain processing in fibromyalgia, we gave fibromyalgia patients a 2.5 kg stimulus to their thumb and asked them how much it hurt on a 0 to 20 visual analog pain scale. We knew that they would experience moderate pain at the same level of pressure that non fibromyalgia patients, healthy controls, experienced no pain. So we put the fibromyalgia patients in the scanner and gave them the low amount of pressure, which in them led to moderate pain, and then gave a group of healthy controls the same amount of pressure (which they rated as barely painful), and then the same amount of pain (by giving them twice as much pressure).

The hypothesis was very simple. If we saw similar neuronal activation patterns in fibromyalgia patients getting the low pressure (which they felt as moderately painful), and the controls getting the same amount of pressure (which they barely felt), then that would indicate that fibromyalgia is some type of a perceptual problem, because although the fibromyalgia patients were having the same brain activation patterns, they were perceiving it differently. In contrast, we saw that the fibromyalgia patient's brain activation patterns were very similar with 2.5 kg of pressure as the controls getting 4.5 kg of pressure. This was the first objective evidence that there is augmented central pain processing in people with fibromyalgia.14 We published another functional MRI study a couple of years ago that showed that the level of depression that a fibromyalgia patient has doesn't at all influence the level of pain in the sensory areas of the brain.15 That suggests that depression and pain, when they are present simultaneously, are really somewhat independent constructs. We also have seen evidence of this in the clinical trials of drugs that are mixed reuptake inhibitors or tricyclics in that whether someone is depressed or not doesn't predict at all whether they're going to respond to one of these drugs as an analgesic.16

In contrast, how people think about their pain might actually influence the sensory processing of pain. In another fMRI study, we showed that fibromyalgia patients that catastrophize actually have augmented neuronal activation in the secondary somatosensory cortex.17 Dave Williams in our group is just finishing a NIH-funded study that does functional imaging at baseline in fibromyalgia patients who have an external locus of pain control and then gives them several brief interventions to increase their locus of control. We hypothesize that changing patient's cognitions (in this case locus of pain control) will change the processing of pain in the brain, even in brain regions thought to be involved in the sensory processing of pain. Finally, we performed another fMRI study showing that individuals with chronic idiopathic low back pain (low back pain with normal lumbar MRIs) were indistinguishable from fibromyalgia patients with respect to their pain sensitivity at their thumbnail and with respect to their functional MRI findings.18 In aggregate, these and many other studies in this spectrum of illness suggest that there is neurobiological evidence of augmented central pain processing, and that in this setting, individuals can experience pain even without appropriate peripheral nociceptive input.

From - Fibromyalgia: Update on Mechanisms and Management JCR: Journal of Clinical Rheumatology:Volume 13(2)April 2007pp 102-109 Clauw, Daniel J. MD From the *Division of Rheumatology, Chronic Pain and Fatigue Research Center, Clinical and Translational Research, University of Michigan Medical Center, Ann Arbor, Michigan. From Rheumatology Grand Rounds at Rush University Medical Center, Chicago, IL, USA. Editors: Robert S. Katz, MD, and Joel A. Block, MD. E-mail: . PMID: 17414543

REFERENCES 12. Kosek E, Hansson P. Modulatory influence on somatosensory perception from vibration and heterotopic noxious conditioning stimulation (HNCS) in fibromyalgia patients and healthy subjects. Pain 1997;70:41-51. 13. Julien N, Goffaux P, Arsenault P, et al. Widespread pain in fibromyalgia is related to a deficit of endogenous pain inhibition. Pain 2005;114:295-302. 14. Gracely RH, Petzke F, Wolf JM, et al. Functional magnetic resonance imaging evidence of augmented pain processing in fibromyalgia. Arthritis Rheum. 2002;46:1333-1343. 15. Giesecke T, Gracely RH, Williams DA, et al. The relationship between depression, clinical pain, and experimental pain in a chronic pain cohort. Arthritis Rheum. 2005;52:1577-1584. 16. Arnold LM, Lu Y, Crofford LJ, et al. A double-blind, multicenter trial comparing duloxetine with placebo in the treatment of fibromyalgia patients with or without major depressive disorder. Arthritis Rheum. 2004;50:2974-2984. 17. Gracely RH, Geisser ME, Giesecke T, et al. Pain catastrophizing and neural responses to pain among persons with fibromyalgia. Brain. 2004;127:835-843. [Fulltext Link] [Medline Link] [CrossRef] [Context Link] 18. Giesecke T, Gracely RH, Grant MA, et al. Evidence of augmented central pain processing in idiopathic chronic low back pain. Arthritis Rheum. 2004;50:613-623.


Search Website

  • Loading