Fibromyalgia Disability: Medical Evidence That Supports the New Neural Sensitization Paradigm

Is fibromyalgia real? What kind of “disease” is it?

When first defined by the American College of Rheumatology in 1990,¹ fibromyalgia syndrome (FMS) was viewed as a rheumatological illness– a matter of sore muscles. The ACR Criteria require: 1. a history of widespread chronic pain in 4 quadrants of the body and 2. abnormal tenderness at 11 or more of 18 designated anatomic sites, called tender points. The tender points are areas of musculotendinous insertion that are normally more sensitive to painful stimuli than are other areas. For many persons with fibromyalgia their increased sensitivity to pain affects only the muscles. However, for many others, increased sensitivity also includes a much broader range of symptoms including the following:^2-6

• Reduced physical stamina and fatigue
• Non-restorative sleep
• Irritable bowel syndrome
• Chronic headache
• Impaired memory and concentration
• Orthostatic hypotension and/or postural orthostatic tachycardia
• Vulvodynia
• Interstitial cystitis
• Anxiety disorders and/or depression.

Evidence that fibromyalgia is a neural disorder.

No one disputes that fibromyalgia patients report that mild stimuli cause severe pain; we call this hyperalgesia. They also report that stimuli which shouldn’t normally cause pain, are to them painful. We call this allodynia. But how do we know that patients are not just “making it up”. Do they actually experience the pain they report? This is a fair question since most patients “look well” and speak easily despite their reported pain.

Several lines of research now provide objective evidence of physical abnormalities in the pain signaling pathways of fibromyalgia patients. These confirm the patients’ self-reports. For example, Gracely measured regional blood flow in the brain by functional MRI. In response to low level pressure fibromyalgia patients had increased regional blood flow in multiple areas of the brain. These changes in blood flow coincided with the patient’s report of pain. The same modest pressures, when applied to controls, did not cause pain and did not cause much cerebral blood flow alteration. The authors concluded that fibromyalgia is characterized by cortical or sub-cortical augmentation of pain processing

Gibson, using cerebral evoked potentials also confirmed the increased pain sensitivity of fibromyalgia patients, as have several others.^10-14 Staud and colleagues have published many papers on the phenomenon of temporal summation or wind-up.^15-17 Temporal summation means that pain intensity increases when as you repeatedly apply the same intensity of painful stimulus. Both FMS patients and normal show temporal summation, but their patterns are different. FMS patients report pain at much lower stimulus intensity than do normals. As we repeat the initial stimulus, pain increases more rapidly than it does for controls. Once the stimulus is stopped, pain decays more slowly. If a very low level of stimulus is maintained, FMS pain continues indefinitely. Controls stop feeling pain despite continuing even if we continue such a low level stimulus.

If healthy persons are tested both before and after intensive exercise, their sensitivity to pain decreases after exercise. For persons with fibromyalgia, it’s just the opposite. Vigorous exercise increases sensitivity to pain. These are all documented differences in the pain sensitivity of fibromyalgia compared to that in controls. Cerebrospinal fluid studies also document objective changes with FMS.^18-20 These include:

• An increased level of substance P, a pro-inflammatory mediator
• An increased level of nerve growth factors
• An increased level of CFS opiate levels
• A reduced CFS levels of the neurohormone, Serotonin.

We also have animal models in which local injury can induce a diffusely increased sensitivity to pain similar to fibromyalgia. Activation of NMDA receptors plays a central role in inducing experimental fibromyalgia. In animals Ketamine, an NMDA antagonist can prevent neural sensitization. In humans, ketamine improves fibromyalgia pain in about 50% of patients.^21-23

Taken together these studies confirm that fibromyalgia patients actually feel the pain they report, and that abnormal neural sensitization plays a central role. But, if FMS is mainly physical, psychological factors can also play a role. About half of all fibromyalgia patients become anxious or depressed as the result of their chronic illness. Also, a history of depression, anxiety and/or post-traumatic stress disorder is more frequent among people who develop FMS than it is in controls. However, perhaps half of patients with fibromyalgia have no personal history of depression or anxiety and do not develop mood disorders, despite continuing illness.

While several anti-depressant medicines can improve FMS pain, most often anti-depressants improve the fibromyalgia patient’s mood, but do not markedly reduce their level of pain. Our best explanation is that fibromyalgia and disorders of mood share common risk factors. When both are present, each tends to make the other worse. This is a more complex and holistic model than it“s all in your head”.

Dr. Hudson, a leading expert concludes:

“...our data are not consistent with the hypothesis that FMS is caused simply by mood disorder; rather, they are consistent with the hypothesis that FMS and mood disorders share important common – and possibly heritable causal factors.”

The bottom line for the family physician: This is a physical not mainly a mental illness. But, when anxiety, depression, poor coping skills, etc co-occur with fibromyalgia, it is important to give each the attention it deserves. It is also important to avoid the common error of blaming the patient for the frustration and complexities of this illness.²⁴

References:

¹Wolfe, F, Smythe, H, Yunus, M et. al. The American College of Rheumatologiy 1990 criteria for the classification of fibromyalgia: Report of the Multicenter Criteria Committee Arthritis Rheum 1990;33:160–72
²Clauw, D, Crofford, L, Chronic widespread pain and fibromyalgia: what we know, and what we need to know, Best Practice & Research Clinical Rheumatology 2003; 17:685-701
³Bennett, R, Emerging Concepts in the Neurobiology of Chronic Pain: Evidence for Abnormal Sensory Processing in Fibromyalgia, Mayo Clin Proc 1999;74:385-98
⁴Russell IJ, Editor, The Fibromyalgia Syndrome: A Clinical Case Definition for Practitioners, Journal of Musculoskeletal Pain, 2003;11:1-107
⁵Clauw, D, Bursitis, Tendinitis, Myofascial Pain, and Fibromyalgia chapter in Rakel R and Bope E, Eds, Conn’s Current Therapy 2005, Elsevier Saunders, 2005
⁶Bennett, R, Disabling Fibromyalgia: Appearance versus Reality, Journal of Rheumatology 1993:20:1821-2
⁷Gracely R Petzke F Wolf J et. al. Functional magnetic resonance imaging evidence of augmented pain processing in fibromyalgia, Arthritis Rheum 2002;46:1333-43