The recent study by Loggia et al ([1]) has design problems that may negate the authors' conclusions. First, they chose a control group composed of healthy pain-free individuals rather than a group with chronic pain of peripheral tissue origin. As in several other studies of pain processing ([2-5]), use of a normal control group eliminates, at the design level, the possibility of determining whether brain circuitry alterations in patients labeled as having fibromyalgia differ from those in patients with pain-causing disorders known to be peripheral and nociceptive.

Second, the pain-free control group differed from the study group not only in the presence or absence of chronic pain but also (and markedly so) in indices of depression and fatigue, as shown in Table 1 ([1]). These differences may add important confounders to cerebral imaging ([6, 7]). Unless such variables are matched in the control group, they may introduce indeterminacy into the interpretation of imaging and psychophysical findings. The proper controls thus should be patients with chronic peripheral pain accompanied by depression.

Furthermore, the authors could have extracted a modicum of information, even in the absence of a relevant control group, by displaying a severity-related gradation in the results. The large standard deviations shown in Table 1 suggest that some patients had 6-fold higher scores than others for pain intensity and the number of pain sites. The decision by the Loggia group not to sort the study group results according to pain level may mask discovery of relevant findings such as whether or not there was an ascending response to increased baseline pain or a threshold below which differences were not present.

In summary, the authors' finding of differences from normal controls cannot demonstrate anything unique or aberrant about the study group's pain-processing brain circuitry, nor can the findings be seen as supportive of “augmented central processing,” the primary axiom of the fibromyalgia hypothesis. Without the discovery of distinct differences between patients and carefully matched control subjects with underlying nociceptive peripheral chronic pain, speculative claims of brain circuitry disruption that is unique to the group with fibromyalgia cannot be substantiated.

  • 1
    Loggia ML, Berna C, Kim J, Cahalan CM, Gollub RL, Wasan AD, et al.Disrupted brain circuitry for pain-related reward/punishment in fibromyalgia.Arthritis Rheumatol2014;66:20312.
  • 2
    Jensen KB, Srinivasan P, Spaeth R, Tan Y, Kosek E, Petzke F, et al.Overlapping structural and functional brain changes in patients with long-term exposure to fibromyalgia pain.Arthritis Rheum2013;65:3293303.
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    Gracely RH, Petzke F, Wolf M, Clauw D.Functional magnetic resonance imaging evidence of augmented pain processing in fibromyalgia.Arthritis Rheum2002;46:133343.
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    Napadow V, Kim J, Clauw DJ, Harris RE.Intrinsic brain connectivity in fibromyalgia is associated with chronic pain intensity.Arthritis Rheum2010;62:254555.
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    Giesecke T, Gracely RH, Grant M, Nachemson A, Petzke F, Williams DA, et al.Evidence of augmented central pain processing in idiopathic chronic low back pain.Arthritis Rheum2004;50;61323.
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    Greicius MD, Flores BH, Menon V, Glover GH, Solvason HB, Kenna H, et al.Resting-state functional connectivity in major depression: abnormally increased contributions from subgenual cingulate cortex and thalamus.Biol Psychiatry2007;62:42937.
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    De Lange FP, Kalkman JS, Bleijenberg G, Hagoort P, van der Werf SP, van der Meer JW, et al.Neural correlates of the chronic fatigue syndrome: an fMRI study.Brain2004;127:194857.