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Imaging Pain in Arthritis: Advances in Structural and Functional Neuroimaging

  • Pain Aspects of Arthritis (DA Walsh and S Kelly, Section Editors)
  • Published:
Current Pain and Headache Reports Aims and scope Submit manuscript

An Erratum to this article was published on 17 October 2012

Abstract

Arthritis is a heterogeneous disease characterized by joint stiffness, swelling, and pain. Although primarily considered a peripheral joint disease, the severity of pain reported by arthritis patients does not always reflect the extent of joint pathology detectable by conventional means. Using structural and functional brain imaging techniques, a growing number of evolving neuroimaging methods are providing insight into these observed discrepancies at different time-scales. Of these methods, functional magnetic resonance imaging is exploited for short-term evoked pain examination and treatment evaluation; ‘resting-state’ approaches provide insight into fluctuations in pain; perfusion imaging captures elements of on-going clinical pain; and morphological brain assessment provides evidence for long-term structural changes in the brain associated with chronic pain. Further insight into arthritic pain processing at the brain-systems level could in the future be provided by combined neuroimaging approaches, specifically investigating the interactions between functional and structural alterations.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Kellgren JH, Lawrence JS. Rheumatism in miners. II. X-ray study. Br J Ind Med. 1952;9:197–207.

    PubMed  CAS  Google Scholar 

  2. Kean WF, Kean R, Buchanan WW. Osteoarthritis: symptoms, signs and source of pain. Inflammopharmacology. 2004;12:3–31.

    Article  PubMed  CAS  Google Scholar 

  3. Gwilym SE, Pollard TC, Carr AJ. Understanding pain in osteoarthritis. J Bone Joint Surg Br. 2008;90:280–7.

    Article  PubMed  CAS  Google Scholar 

  4. Wylde V, Hewlett S, Learmonth ID, et al. Persistent pain after joint replacement: prevalence, sensory qualities, and postoperative determinants. Pain. 2011;152:566–72.

    Article  PubMed  Google Scholar 

  5. Moseley JB, O’Malley K, Petersen NJ, et al. A controlled trial of arthroscopic surgery for osteoarthritis of the knee. N Engl J Med. 2002;347:81–8.

    Article  PubMed  Google Scholar 

  6. Arendt-Nielsen L, Nie H, Laursen MB, et al. Sensitization in patients with painful knee osteoarthritis. Pain. 2010;149:573–81.

    Article  PubMed  Google Scholar 

  7. Lee MC, Zambreanu L, Menon DK, et al. Identifying brain activity specifically related to the maintenance and perceptual consequence of central sensitization in humans. J Neurosci. 2008;28:11642–9.

    Article  PubMed  CAS  Google Scholar 

  8. Tracey I, Mantyh PW. The cerebral signature for pain perception and its modulation. Neuron. 2007;55:377–91.

    Article  PubMed  CAS  Google Scholar 

  9. Schweinhardt P, Kalk N, Wartolowska K, et al. Investigation into the neural correlates of emotional augmentation of clinical pain. Neuroimage. 2008;40:759–66.

    Article  PubMed  Google Scholar 

  10. • Gwilym SE, Keltner JR, Warnaby CE, et al. Psychophysical and functional imaging evidence supporting the presence of central sensitization in a cohort of osteoarthritis patients. Arthritis Rheum. 2009;61:1226–34. Brainstem revealed as potential mediator of central sensitisation in OA.

    Article  PubMed  Google Scholar 

  11. Parks EL, Geha PY, Baliki MN, et al. Brain activity for chronic knee osteoarthritis: Dissociating evoked pain from spontaneous pain. Eur J Pain 2011. Identified the targets of anti-inflammatory therapy in OA patients as the prefrontal-limbic brain areas.

  12. Wartolowska K, Schweinhardt P, Wordsworth P, et al. Pain processing in rheumatoid arthritis patients successfully treated with anti-TNF. The British Society for Rheumatology. Birmingham, 2007

  13. • Hess A, Axmann R, Rech J, et al. Blockade of TNF-alpha rapidly inhibits pain responses in the central nervous system. Proc Natl Acad Sci U S A. 2011;108:3731–6. TNF-alpha neutralization occurs at level of brain before it acts at the joint.

    Article  PubMed  CAS  Google Scholar 

  14. Drewes AM, Svendsen L, Taagholt SJ, et al. Sleep in rheumatoid arthritis: a comparison with healthy subjects and studies of sleep/wake interactions. Br J Rheumatol. 1998;37:71–81.

    Article  PubMed  CAS  Google Scholar 

  15. Hummel T, Schiessl C, Wendler J, et al. Peripheral and central nervous changes in patients with rheumatoid arthritis in response to repetitive painful stimulation. Int J Psychophysiol. 2000;37:177–83.

    Article  PubMed  CAS  Google Scholar 

  16. Baliki MN, Geha PY, Apkarian AV, et al. Beyond feeling: chronic pain hurts the brain, disrupting the default-mode network dynamics. J Neurosci. 2008;28:1398–403.

    Article  PubMed  CAS  Google Scholar 

  17. • Baliki MN, Baria AT, Apkarian AV. The cortical rhythms of chronic back pain. J Neurosci. 2011;31:13981–90. Evidence for aberrant functional connectivity in chronic back pain patients.

    Article  PubMed  CAS  Google Scholar 

  18. Jones AK, Derbyshire SW. Reduced cortical responses to noxious heat in patients with rheumatoid arthritis. Ann Rheum Dis. 1997;56:601–7.

    Article  PubMed  CAS  Google Scholar 

  19. Kulkarni B, Bentley DE, Elliott R, et al. Arthritic pain is processed in brain areas concerned with emotions and fear. Arthritis Rheum. 2007;56:1345–54.

    Article  PubMed  CAS  Google Scholar 

  20. • Howard MA, Krause K, Khawaja N, et al. Beyond patient reported pain: perfusion magnetic resonance imaging demonstrates reproducible cerebral representation of ongoing post-surgical pain. PLoS One. 2011;6:e17096. First application of arterial spin labelling MRI to identify rCBF increases in a clinical condition.

    Article  PubMed  CAS  Google Scholar 

  21. • Wasan AD, Loggia ML, Chen LQ, et al. Neural correlates of chronic low back pain measured by arterial spin labeling. Anesthesiology. 2011;115:364–74. Arterial spin labelling MRI identified rCBF increases in chronic back pain patients.

    Article  PubMed  Google Scholar 

  22. • Howard MA, Sanders D, Krause K, et al. Alterations in Resting Cerebral Blood Flow Demonstrate Ongoing Pain in Osteoarthritis: An Arterial Spin Labelled Magnetic Resonance Imaging Study. Arthritis Rheum 2012; In press. The only study of arterial spin labelling in arthritis patients finds increased rCBF responses associated with on-going pain in thumb OA.

  23. • Rodriguez-Raecke R, Niemeier A, Ihle K, et al. Brain gray matter decrease in chronic pain is the consequence and not the cause of pain. J Neurosci. 2009;29:13746–50. Reversible brain atrophy identified 4 months after hip repalcement.

    Article  PubMed  CAS  Google Scholar 

  24. • Gwilym SE, Filippini N, Douaud G, et al. Thalamic atrophy associated with painful osteoarthritis of the hip is reversible after arthroplasty: a longitudinal voxel-based morphometric study. Arthritis Rheum. 2010;62:2930–40. Reversible brain atrophy identified 9 months after hip replacement.

    Article  PubMed  Google Scholar 

  25. Ingvar M. Pain and functional imaging. Philos Trans R Soc Lond B Biol Sci. 1999;354:1347–58.

    Article  PubMed  CAS  Google Scholar 

  26. Apkarian AV, Bushnell MC, Treede RD, et al. Human brain mechanisms of pain perception and regulation in health and disease. Eur J Pain. 2005;9:463–84.

    Article  PubMed  Google Scholar 

  27. • Iannetti GD, Mouraux A. From the neuromatrix to the pain matrix (and back). Exp Brain Res. 2010;205:1–12. Critical review of the evidence in favour and against the concept of pain specific neuromatrix.

    Article  PubMed  CAS  Google Scholar 

  28. • Legrain V, Iannetti GD, Plaghki L, et al. The pain matrix reloaded: a salience detection system for the body. Prog Neurobiol. 2011;93:111–24. Proposes a cortical network that acts as a defensive system where the emphasis is no longer on the quality of the sensation elicited by noxious stimuli but on the action prompted by the occurrence of potential threats.

    Article  PubMed  Google Scholar 

  29. • Baliki MN, Schnitzer TJ, Bauer WR, et al. Brain morphological signatures for chronic pain. PLoS One. 2011;6:e26010. Demonstrates potential for decoding condition-specific musculoskeletal pain on the basis of structural brain signatures.

    Article  PubMed  CAS  Google Scholar 

  30. Ploghaus A, Tracey I, Gati JS, et al. Dissociating pain from its anticipation in the human brain. Science. 1999;284:1979–81.

    Article  PubMed  CAS  Google Scholar 

  31. Buffington AL, Hanlon CA, McKeown MJ. Acute and persistent pain modulation of attention-related anterior cingulate fMRI activations. Pain. 2005;113:172–84.

    Article  PubMed  Google Scholar 

  32. Godha D, Shi L, Mavronicolas H. Association between tendency towards depression and severity of rheumatoid arthritis from a national representative sample: the Medical Expenditure Panel Survey. Curr Med Res Opin. 2010;26:1685–90.

    Article  PubMed  Google Scholar 

  33. Axford J, Butt A, Heron C, et al. Prevalence of anxiety and depression in osteoarthritis: use of the Hospital Anxiety and Depression Scale as a screening tool. Clin Rheumatol. 2010;29:1277–83.

    Article  PubMed  Google Scholar 

  34. Edwards RR, Cahalan C, Mensing G, et al. Pain, catastrophizing, and depression in the rheumatic diseases. Nat Rev Rheumatol. 2011;7:216–24.

    Article  PubMed  CAS  Google Scholar 

  35. Apkarian AV, Bushnell MC, Treede RD, et al. Human brain mechanisms of pain perception and regulation in health and disease. Eur J Pain. 2005;9:463–84.

    Article  PubMed  Google Scholar 

  36. • Jensen KB, Kosek E, Petzke F, et al. Evidence of dysfunctional pain inhibition in Fibromyalgia reflected in rACC during provoked pain. Pain. 2009;144:95–100. Dysfunctional pain inhibition associated with chronic musculoskeletal disease.

    Article  PubMed  Google Scholar 

  37. • Burgmer M, Pogatzki-Zahn E, Gaubitz M, et al. Fibromyalgia unique temporal brain activation during experimental pain: a controlled fMRI Study. J Neural Transm. 2010;117:123–31. The role of frontal cortex and PAG in contributing to central sensitisation in FMS.

    Article  PubMed  Google Scholar 

  38. Chen JJ, Wang JY, Chang YM, et al. Regional cerebral blood flow between primary and concomitant fibromyalgia patients: a possible way to differentiate concomitant fibromyalgia from the primary disease. Scand J Rheumatol. 2007;36:226–32.

    Article  PubMed  CAS  Google Scholar 

  39. • Marquand A, Howard M, Brammer M, et al. Quantitative prediction of subjective pain intensity from whole-brain fMRI data using Gaussian processes. Neuroimage. 2010;49:2178–89. Presents a novel algorithmic decoding strategy for fMRI data using Gaussian processes, and extends multivariate classification tools to continuous variables.

    Article  PubMed  Google Scholar 

  40. Richardson EJ, Ness TJ, Doleys DM, et al. Catastrophizing, acceptance, and interference: laboratory findings, subjective report, and pain willingness as a moderator. Health Psychol. 2010;29:299–306.

    Article  PubMed  Google Scholar 

  41. Fox MD, Snyder AZ, Vincent JL, et al. The human brain is intrinsically organized into dynamic, anticorrelated functional networks. Proc Natl Acad Sci U S A. 2005;102:9673–8.

    Article  PubMed  CAS  Google Scholar 

  42. • Napadow V, LaCount L, Park K, et al. Intrinsic brain connectivity in fibromyalgia is associated with chronic pain intensity. Arthritis Rheum. 2010;62:2545–55. Resting-state brain activity within multiple networks associated with spontaneous clinical pain in patients with FM and subjective experiences such as pain may arise from a complex interplay among multiple brain networks.

    Article  PubMed  Google Scholar 

  43. • Jensen KB, Loitoile R, Kosek E, et al. Patients with fibromyalgia display less functional connectivity in the Brain’s pain inhibitory network. Mol Pain. 2012;8:32. Aberrant functional connectivity associated with chronic musculoskeletal disease.

    Article  PubMed  Google Scholar 

  44. Cauda F, Sacco K, Duca S, et al. Altered resting state in diabetic neuropathic pain. PLoS One. 2009;4:e4542.

    Article  PubMed  Google Scholar 

  45. Moldofsky H, Lue FA, Smythe HA. Alpha EEG sleep and morning symptoms in rheumatoid arthritis. J Rheumatol. 1983;10:373–9.

    PubMed  CAS  Google Scholar 

  46. Derbyshire SW, Jones AK, Devani P, et al. Cerebral responses to pain in patients with atypical facial pain measured by positron emission tomography. J Neurol Neurosurg Psychiatry. 1994;57:1166–72.

    Article  PubMed  CAS  Google Scholar 

  47. Tracey I, Johns E. The pain matrix: reloaded or reborn as we image tonic pain using arterial spin labelling. Pain. 2010;148:359–60.

    Article  PubMed  Google Scholar 

  48. • Owen DG, Clarke CF, Ganapathy S, et al. Using perfusion MRI to measure the dynamic changes in neural activation associated with tonic muscular pain. Pain. 2010;148:375–86. Preferential decreases in the affective component of the pain once initial anxiety dissipates.

    Article  PubMed  Google Scholar 

  49. • Segerdahl AR, Xie J, Paterson K, et al. Imaging the neural correlates of neuropathic pain and pleasurable relief associated with inherited erythromelalgia in a single subject with quantitative arterial spin labelling. Pain. 2012;153:1122–7. Confirmed the presence of a temperature-sensitive channelopathy of peripheral neurons and the neural correlates of tonic neuropathic pain and relief in a single subject.

    Article  PubMed  Google Scholar 

  50. Gauthier LV, Taub E, Perkins C, et al. Remodeling the brain: plastic structural brain changes produced by different motor therapies after stroke. Stroke. 2008;39:1520–5.

    Article  PubMed  Google Scholar 

  51. Apkarian AV, Sosa Y, Sonty S, et al. Chronic back pain is associated with decreased prefrontal and thalamic gray matter density. J Neurosci. 2004;24:10410–5.

    Article  PubMed  CAS  Google Scholar 

  52. Kuchinad A, Schweinhardt P, Seminowicz DA, et al. Accelerated brain gray matter loss in fibromyalgia patients: premature aging of the brain? J Neurosci. 2007;27:4004–7.

    Article  PubMed  CAS  Google Scholar 

  53. Schmidt-Wilcke T, Leinisch E, Ganssbauer S, et al. Affective components and intensity of pain correlate with structural differences in gray matter in chronic back pain patients. Pain. 2006;125:89–97.

    Article  PubMed  CAS  Google Scholar 

  54. Schmidt-Wilcke T, Luerding R, Weigand T, et al. Striatal grey matter increase in patients suffering from fibromyalgia–a voxel-based morphometry study. Pain. 2007;132 Suppl 1:S109–16.

    Article  PubMed  Google Scholar 

  55. Lutz J, Jager L, de Quervain D, et al. White and gray matter abnormalities in the brain of patients with fibromyalgia: a diffusion-tensor and volumetric imaging study. Arthritis Rheum. 2008;58:3960–9.

    Article  PubMed  Google Scholar 

  56. May A. Chronic pain may change the structure of the brain. Pain. 2008;137:7–15.

    Article  PubMed  Google Scholar 

  57. Bekkelund SI, Pierre-Jerome C, Husby G, et al. Quantitative cerebral MR in rheumatoid arthritis. AJNR Am J Neuroradiol. 1995;16:767–72.

    PubMed  CAS  Google Scholar 

  58. • Wartolowska K, Hough MG, Jenkinson M, et al. Structural changes of the brain in rheumatoid arthritis. Arthritis Rheum. 2012;64:371–9. Structural atrophy of basal ganglia in patients with RA.

    Article  PubMed  Google Scholar 

  59. Grachev ID, Fredrickson BE, Apkarian AV. Abnormal brain chemistry in chronic back pain: an in vivo proton magnetic resonance spectroscopy study. Pain. 2000;89:7–18.

    Article  PubMed  CAS  Google Scholar 

  60. Harris RE, Clauw DJ. Imaging central neurochemical alterations in chronic pain with proton magnetic resonance spectroscopy. Neurosci Lett. 2012;520:192–6.

    Article  PubMed  CAS  Google Scholar 

  61. Luerding R, Weigand T, Bogdahn U, et al. Working memory performance is correlated with local brain morphology in the medial frontal and anterior cingulate cortex in fibromyalgia patients: structural correlates of pain-cognition interaction. Brain. 2008;131:3222–31.

    Article  PubMed  CAS  Google Scholar 

  62. Buckalew N, Haut MW, Morrow L, et al. Chronic pain is associated with brain volume loss in older adults: preliminary evidence. Pain Med. 2008;9:240–8.

    Article  PubMed  Google Scholar 

  63. Wartolowska K, Tracey I. Neuroimaging as a tool for pain diagnosis and analgesic development. Neurotherapeutics. 2009;6:755–60.

    Article  PubMed  CAS  Google Scholar 

  64. • Wise RG, Preston C. What is the value of human FMRI in CNS drug development? Drug Discov Today. 2010;15:973–80. Review of fMRI in understanding therapeutic mechanisms and providing clinically relevant markers of disease responses to drugs to aid decision-making.

    Article  PubMed  CAS  Google Scholar 

  65. Baliki M, Katz J, Chialvo DR, et al. Single subject pharmacological-MRI (phMRI) study: modulation of brain activity of psoriatic arthritis pain by cyclooxygenase-2 inhibitor. Mol Pain. 2005;1:32.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

The authors are very grateful for the support of Arthritis Research UK.

AKH is supported by the Arthritis Research UK Biomechanics and Bioengineering Centre. RGW is supported by the Higher Education Funding Council for Wales. AMT is supported by Napp Pharmaceutical through an Educational Grant.

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No potential conflicts of interest relevant to this article were reported.

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Authors and Affiliations

  1. Arthritis Research UK Biomechanics and Bioengineering Centre, Cardiff University, Cardiff, CF10 3AX, UK

    Ann K. Harvey & Richard G. Wise

  2. Institute for Infection & Immunity, School of Medicine, Cardiff University, Heath Park Campus, Cardiff, CF14 4XN, UK

    Ann K. Harvey & Ann M. Taylor

  3. CUBRIC, School of Psychology, Cardiff University, Park Place, Cardiff, CF10 3AT, UK

    Ann M. Taylor & Richard G. Wise

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  1. Ann K. Harvey
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  2. Ann M. Taylor
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Correspondence to Richard G. Wise.

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Harvey, A.K., Taylor, A.M. & Wise, R.G. Imaging Pain in Arthritis: Advances in Structural and Functional Neuroimaging. Curr Pain Headache Rep 16, 492–501 (2012). https://doi.org/10.1007/s11916-012-0297-4

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