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Central Neuroimaging of Pain

  • Sean C. Mackey
    Affiliations
    Redlich Professor of Pain Medicine, Departments of Anesthesiology, Pain and Perioperative Medicine/Neurosciences/Neurology (by courtesy), Stanford University School of Medicine, Standford, CA
    Chief, Division of Pain Medicine, Stanford University School of Medicine, Standford, CA
    Director, Stanford Systems Neuroscience and Pain Lab, Stanford University School of Medicine, Standford, CA
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      Central neuroimaging of pain has emerged as an effective way to assess central nervous system correlates and potentially also to characterize mechanisms of human pain perception, modulation, and plasticity. Central neuroimaging has allowed us to open windows into the brain to observe the roles of attention,
      • Petrovic P.
      • Petersson K.M.
      • Ghatan P.H.
      • Stone-Elander S.
      • Ingvar M.
      Pain-related cerebral activation is altered by a distracting cognitive task.
      anticipation,
      • Koyama T.
      • McHaffie J.G.
      • Laurienti P.J.
      • Coghill R.C.
      The subjective experience of pain: Where expectations become reality.
      fear/anxiety,
      • Ochsner K.N.
      • Ludlow D.H.
      • Knierim K.
      • Hanelin J.
      • Ramachandran T.
      • Glover G.C.
      • Mackey S.C.
      Neural correlates of individual differences in pain-related fear and anxiety.
      placebo,
      • Benedetti F.
      • Maybert H.S.
      • Wager T.D.
      • Stohler C.S.
      • Zubieta J.K.
      Neurobiological mechanisms of the placebo effect.
      direct control,
      • deCharms R.C.
      • Maeda F.
      • Glover G.H.
      • Ludlow D.
      • Pauly S.M.
      • Soneji D.
      • Gabrieli J.D.
      • Mackey S.C.
      Control over brain activation and pain learned by using real-time functional MRI.
      and other factors. We now better understand the changes in the brain associated with chronicity of pain,
      • Apkarian A.V.
      • Sosa Y.
      • Sonty S.
      • Levy R.M.
      • Harden R.N.
      • Parrish T.B.
      • Gitelman D.R.
      Chronic back pain is associated with decreased prefrontal and thalamic gray matter density.
      • Younger J.W.
      • Shen Y.F.
      • Goddard G.
      • Mackey S.C.
      Chronic myofascial temporomandibular pain is associated with neural abnormalities in the trigeminal and limbic systems.
      the effects of opioids,
      • Upadhyay J.
      • Maleki N.
      • Potter J.
      • Elman I.
      • Rudrauf D.
      • Knudsen J.
      • Wallin D.
      • Pendse G.
      • McDonald L.
      • Griffin M.
      • Anderson J.
      • Nutile L.
      • Renshaw P.
      • Weiss R.
      • Becerra L.
      • Borsook D.
      Alterations in brain structure and functional connectivity in prescription opioid-dependent patients.
      • Younger J.W.
      • Chu L.F.
      • D'Arcy N.T.
      • Trott K.E.
      • Jastrzab L.E.
      • Mackey S.C.
      Prescription opioid analgesics rapidly change the human brain.
      and effects of nonopioid therapies.
      • Seminowicz D.A.
      • Wideman T.H.
      • Naso L.
      • Hatami-Khoroushahi Z.
      • Fallatah S.
      • Ware M.A.
      • Jarzem P.
      • Bushnell M.C.
      • Shir Y.
      • Ouellet J.A.
      • Stone L.S.
      Effective treatment of chronic low back pain in humans reverses abnormal brain anatomy and function.
      The benefits we have gained from using central neuroimaging clearly advance our scientific knowledge of pain. However, the authors of 2 articles in this issue of the Journal of Pain suggest that perhaps our use of neuroimaging overreaches in our attempt to address 2 important questions: 1) Does brain neuroimaging replace self-reporting of pain or will it do so in the future? and 2) Do central neuroimaging findings alone define pain as a disease? The authors of these articles
      • Robinson M.E.
      • Staud R.
      • Price D.D.
      Pain Measurement and brain activity: Will neuroimages replace pain ratings?.
      • Sullivan M.D.
      • Cahan A.
      • Derbyshire S.
      • Loeser J.D.
      What does it mean to call chronic pain a brain disease?.
      make compelling arguments that the answers to both these questions are an emphatic “No.” I would agree. However, it would be too easy to lose sight of neuroimaging’s potential role in augmenting self-report of pain, detecting or classifying pain and pain states, and helping define chronic pain as a disease. The story is much richer and deserves further consideration.
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      Linked Article

      • What Does It Mean to Call Chronic Pain a Brain Disease?
        The Journal of PainVol. 14Issue 4
        • Preview
          Multiple investigators have recently asked whether neuroimaging has shown that chronic pain is a brain disease. We review the clinical implications of seeing chronic pain as a brain disease. Abnormalities noted on imaging of peripheral structures have previously misled the clinical care of patients with chronic pain. We also cannot assume that the changes associated with chronic pain on neuroimaging are causal. When considering the significance of neuroimaging results, it is important to remember that “disease” is a concept that arises out of clinical medicine, not laboratory science.
        • Full-Text
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      • Pain Measurement and Brain Activity: Will Neuroimages Replace Pain Ratings?
        The Journal of PainVol. 14Issue 4
        • Preview
          Arguments made for the advantages of replacing pain ratings with brain-imaging data include assumptions that pain ratings are less reliable and objective and that brain image data would greatly benefit the measurement of treatment efficacy. None of these assumptions are supported by available evidence. Self-report of pain is predictable and does not necessarily reflect unreliability or error. Because pain is defined as an experience, magnitudes of its dimensions can be estimated by well-established methods, including those used to validate brain imaging of pain.
        • Full-Text
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      • Reply to Commentaries
        The Journal of PainVol. 14Issue 4
        • Preview
          We appreciate the thoughtful comments of Drs. Mackey and Davis.1,2 However, we would like to draw the reader’s attention to a few aspects of their responses that may help to clarify differences between us.
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      • Reply to Commentary
        The Journal of PainVol. 14Issue 4
        • Preview
          The commentary by Sean Mackey3 makes several interesting points, many of which show strong agreement with the points raised by all of the other articles. Within the early part of his article he agrees that brain neuroimaging will not replace self-reporting of pain nor will it do so in the future and that central neuroimaging findings alone do not define pain as a disease. He then raises concerns that, based on our arguments forcefully presented to readers,6 they “may lose sight of the real value of central neuroimaging—a way to augment self-report of pain and a potential, objective [italics ours] biomarker of pain and pain treatment.”3 There are several points we wish to make about Mackey’s concerns that we think help clarify our agreements and disagreements.
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