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Cognitive and emotional control of pain and its disruption in chronic pain

Subjects

Key Points

  • Pain experience can be profoundly influenced by emotional states and attentional direction. Multiple brain regions involved in pain processing are also crucial for emotion and attention.

  • Emotional modulation of pain seems to be controlled by a fronto–periaqueductal grey–brainstem circuit that can increase or decrease pain experience depending on the emotion being experienced: for example, empathy for another's pain can increase an individual's own pain sensation. Attention can reduce pain via distraction and is purported to depend on insula–parietal–somatosensory corticocortical pathways.

  • Both emotional and attentional modulation of pain can be harnessed by non-pharmacological interventions such as yoga, meditation and the placebo effect. Indeed, even expectation of relief activates descending endogenous opioidergic circuitry.

  • When pain becomes chronic, structural changes are seen in multiple brain regions involved in emotional and attentional aspects of pain modulation, possibly leading to a diminished ability in pain regulation.

  • There is also evidence that disruption of endogenous pain modulatory systems by chronic pain alters cognitive and emotional processing in patients with pain, leading to impairments in performance on decision-making and learning tasks.

  • The neurochemical bases for these changes are not yet well understood, although evidence suggests possible roles for excitotoxicity and neuroinflammation in impaired neuronal integrity and firing properties.

  • However, successful treatment of chronic pain — such as by hip replacement or back surgery — can reverse the pain-related reductions in grey matter. There are tantalizing hints that psychology-based treatments such as meditation may also act in a neuroprotective manner to prevent or reverse these pain-related changes in brain structure and function.

Abstract

Chronic pain is one of the most prevalent health problems in our modern world, with millions of people debilitated by conditions such as back pain, headache and arthritis. To address this growing problem, many people are turning to mind–body therapies, including meditation, yoga and cognitive behavioural therapy. This article will review the neural mechanisms underlying the modulation of pain by cognitive and emotional states — important components of mind–body therapies. It will also examine the accumulating evidence that chronic pain itself alters brain circuitry, including that involved in endogenous pain control, suggesting that controlling pain becomes increasingly difficult as pain becomes chronic.

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Figure 1: Feedback loops between pain, emotions and cognition.
Figure 2: Afferent pain pathways include multiple brain regions.
Figure 3: Attentional and emotional factors modulate pain perception via different pathways.
Figure 4: Consistently identified changes in the brains of patients with chronic pain.

References

  1. Bingel, U. et al. The effect of treatment expectation on drug efficacy: imaging the analgesic benefit of the opioid remifentanil. Sci. Transl. Med. 3, 70ra14 (2011).

    Article  PubMed  CAS  Google Scholar 

  2. Benedetti, F., Mayberg, H. S., Wager, T. D., Stohler, C. S. & Zubieta, J. K. Neurobiological mechanisms of the placebo effect. J. Neurosci. 25, 10390–10402 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Villemure, C. & Bushnell, M. C. Cognitive modulation of pain: how do attention and emotion influence pain processing? Pain 95, 195–199 (2002).

    Article  PubMed  Google Scholar 

  4. Villemure, C. & Bushnell, M. C. Mood influences supraspinal pain processing separately from attention. J. Neurosci. 29, 705–715 (2009). This is the first study to dissociate the circuitry involved in emotional and attentional modulation of pain.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Loggia, M. L., Mogil, J. S. & Bushnell, M. C. Empathy hurts: compassion for another increases both sensory and affective components of pain perception. Pain 136, 168–176 (2008).

    Article  PubMed  Google Scholar 

  6. Schweinhardt, P. & Bushnell, M. C. Pain imaging in health and disease — how far have we come? J. Clin. Invest. 120, 3788–3797 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Hölzel, B. K. et al. Mindfulness practice leads to increases in regional brain gray matter density. Psychiatry Res. 191, 36–43 (2011).

    Article  PubMed  Google Scholar 

  8. Grant, J. A., Courtemanche, J., Duerden, E. G., Duncan, G. H. & Rainville, P. Cortical thickness and pain sensitivity in zen meditators. Emotion 10, 43–53 (2010).

    Article  PubMed  Google Scholar 

  9. Pagnoni, G. & Cekic, M. Age effects on gray matter volume and attentional performance in Zen meditation. Neurobiol. Aging 28, 1623–1627 (2007).

    Article  PubMed  Google Scholar 

  10. Mackey, A. P., Whitaker, K. J. & Bunge, S. A. Experience-dependent plasticity in white matter microstructure: reasoning training alters structural connectivity. Front. Neuroanat. 6, 32 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  11. Luders, E. et al. Bridging the hemispheres in meditation: thicker callosal regions and enhanced fractional anisotropy (FA) in long-term practitioners. Neuroimage 61, 181–187 (2012).

    Article  PubMed  Google Scholar 

  12. Lutz, A., McFarlin, D. R., Perlman, D. M., Salomons, T. V. & Davidson, R. J. Altered anterior insula activation during anticipation and experience of painful stimuli in expert meditators. Neuroimage 64, 538–546 (2013).

    Article  PubMed  Google Scholar 

  13. Apkarian, A. V., Bushnell, M. C., Treede, R. D. & Zubieta, J. K. Human brain mechanisms of pain perception and regulation in health and disease. Eur. J. Pain 9, 463–484 (2005).

    PubMed  Google Scholar 

  14. Friedman, D. P., Murray, E. A., O'Neill, J. B. & Mishkin, M. Cortical connections of the somatosensory fields of the lateral sulcus of macaques: evidence for a corticolimbic pathway for touch. J. Comp. Neurol. 252, 323–347 (1986).

    Article  CAS  PubMed  Google Scholar 

  15. Rausell, E. & Jones, E. G. Histochemical and immunocytochemical compartments of the thalamic VPM nucleus in monkeys and their relationship to the representational map. J. Neurosci. 11, 210–225 (1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Apkarian, A. V. & Shi, T. in Pain Mechanisms and Management (eds Ayrapetyan, S. N. & Apkarian, A. V.) 212–220 (IOS Press, 1998).

    Google Scholar 

  17. Craig, A. D. & Dostrovsky, J. O. Thermoreceptive lamina I trigeminothalamic neurons project to the nucleus submedius in the cat. Exp. Brain Res. 85, 470–474 (1991).

    Article  CAS  PubMed  Google Scholar 

  18. Dum, R. P., Levinthal, D. J. & Strick, P. L. The spinothalamic system targets motor and sensory areas in the cerebral cortex of monkeys. J. Neurosci. 29, 14223–14235 (2009). This is the first paper to show all of the cortical targets of the spinothalamic system.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Saab, C. Y. & Willis, W. D. The cerebellum: organization, functions and its role in nociception. Brain Res. Brain Res. Rev. 42, 85–95 (2003).

    Article  PubMed  Google Scholar 

  20. Monconduit, L. & Villanueva, L. The lateral ventromedial thalamic nucleus spreads nociceptive signals from the whole body surface to layer I of the frontal cortex. Eur. J. Neurosci. 21, 3395–3402 (2005).

    Article  PubMed  Google Scholar 

  21. Becerra, L., Breiter, H. C., Wise, R., Gonzalez, R. G. & Borsook, D. Reward circuitry activation by noxious thermal stimuli. Neuron 32, 927–946 (2001).

    Article  CAS  PubMed  Google Scholar 

  22. Baliki, M. N., Geha, P. Y., Fields, H. L. & Apkarian, A. V. Predicting value of pain and analgesia: nucleus accumbens response to noxious stimuli changes in the presence of chronic pain. Neuron 66, 149–160 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Bernard, J. F., Bester, H. & Besson, J. M. Involvement of the spino-parabrachio -amygdaloid and -hypothalamic pathways in the autonomic and affective emotional aspects of pain. Prog. Brain Res. 107, 243–255 (1996).

    Article  CAS  PubMed  Google Scholar 

  24. Dunckley, P. et al. A comparison of visceral and somatic pain processing in the human brainstem using functional magnetic resonance imaging. J. Neurosci. 25, 7333–7341 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Basbaum, A. I. & Fields, H. L. Endogenous pain control systems: brainstem spinal pathways and endorphin circuitry. Annu. Rev. Neurosci. 7, 309–338 (1984).

    Article  CAS  PubMed  Google Scholar 

  26. Kenshalo, D. R. Jr & Isensee, O. Responses of primate SI cortical neurons to noxious stimuli. J. Neurophysiol. 50, 1479–1496 (1983).

    Article  PubMed  Google Scholar 

  27. Kenshalo, D. R. Jr, Chudler, E. H., Anton, F. & Dubner, R. SI nociceptive neurons participate in the encoding process by which monkeys perceive the intensity of noxious thermal stimulation. Brain Res. 454, 378–382 (1988).

    Article  PubMed  Google Scholar 

  28. Chudler, E. H., Anton, F., Dubner, R. & Kenshalo, D. R. Jr. Responses of nociceptive SI neurons in monkeys and pain sensation in humans elicited by noxious thermal stimulation: effect of interstimulus interval. J. Neurophysiol. 63, 559–569 (1990).

    Article  CAS  PubMed  Google Scholar 

  29. Ploner, M., Freund, H. J. & Schnitzler, A. Pain affect without pain sensation in a patient with a postcentral lesion. Pain 81, 211–214 (1999).

    Article  CAS  PubMed  Google Scholar 

  30. Greenspan, J. D., Lee, R. R. & Lenz, F. A. Pain sensitivity alterations as a function of lesion location in the parasylvian cortex. Pain 81, 273–282 (1999).

    Article  CAS  PubMed  Google Scholar 

  31. Penfield, W. & Boldrey, E. Somatic motor and sensory representation in the cerebral cortex of man as studied by electrical stimulation. Brain 60, 389–443 (1937).

    Article  Google Scholar 

  32. MacLean, P. D. Psychosomatic disease and the “visceral brain.” Recent developments bearing on the Papez theory of emotion. Psychosom. Med. 11, 338–353 (1949).

    Article  CAS  PubMed  Google Scholar 

  33. Foltz, E. L. & Lowell, E. W. Pain “relief” by frontal cingulumotomy. J. Neurosurg. 19, 89–100 (1962).

    Article  CAS  PubMed  Google Scholar 

  34. Foltz, E. L. & White, L. E. The role or rostral cingulumotomy in “pain” relief. Int. J. Neurol. 6, 353–373 (1968).

    CAS  PubMed  Google Scholar 

  35. Corkin, S. & Hebben, N. Subjective estimates of chronic pain before and after psychosurgery or treatment in a pain unit. Pain 1, S150 (1981).

    Article  Google Scholar 

  36. Berthier, M., Starkstein, S. & Leiguarda, R. Asymbolia for pain: a sensory-limbic disconnection syndrome. Ann. Neurol. 24, 41–49 (1988).

    Article  CAS  PubMed  Google Scholar 

  37. Rainville, P., Duncan, G. H., Price, D. D., Carrier, B. & Bushnell, M. C. Pain affect encoded in human anterior cingulate but not somatosensory cortex. Science 277, 968–971 (1997). This is the first study to demonstrate the separation of sensory and affective pain processing in the cerebral cortex.

    Article  CAS  PubMed  Google Scholar 

  38. Tolle, T. R. et al. Region-specific encoding of sensory and affective components of pain in the human brain: a positron emission tomography correlation analysis. Ann. Neurol. 45, 40–47 (1999).

    Article  CAS  PubMed  Google Scholar 

  39. Zubieta, J. K. et al. Regional μ opioid receptor regulation of sensory and affective dimensions of pain. Science 293, 311–315 (2001). This study provides the first demonstration of the relevance of forebrain opioid receptors to pain modulation.

    Article  CAS  PubMed  Google Scholar 

  40. Ostrowsky, K. et al. Representation of pain and somatic sensation in the human insula: a study of responses to direct electrical cortical stimulation. Cereb. Cortex 12, 376–385 (2002).

    Article  PubMed  Google Scholar 

  41. Craig, A. D. Significance of the insula for the evolution of human awareness of feelings from the body. Ann. NY Acad. Sci. 1225, 72–82 (2011).

    Article  PubMed  Google Scholar 

  42. Baliki, M. N., Geha, P. Y. & Apkarian, A. V. Parsing pain perception between nociceptive representation and magnitude estimation. J. Neurophysiol. 101, 875–887 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Lamm, C., Decety, J. & Singer, T. Meta-analytic evidence for common and distinct neural networks associated with directly experienced pain and empathy for pain. Neuroimage 54, 2492–2502 (2011).

    Article  PubMed  Google Scholar 

  44. Cheng, Y., Chen, C., Lin, C. P., Chou, K. H. & Decety, J. Love hurts: an fMRI study. Neuroimage 51, 923–929 (2010).

    Article  PubMed  Google Scholar 

  45. Langford, D. J. et al. Social modulation of pain as evidence for empathy in mice. Science 312, 1967–1970 (2006).

    Article  CAS  PubMed  Google Scholar 

  46. Rosen, G., Willoch, F., Bartenstein, P., Berner, N. & Rosjo, S. Neurophysiological processes underlying the phantom limb pain experience and the use of hypnosis in its clinical management: an intensive examination of two patients. Int. J. Clin. Exp. Hypn. 49, 38–55 (2001).

    Article  CAS  PubMed  Google Scholar 

  47. Porro, C. A. et al. Does anticipation of pain affect cortical nociceptive systems? J. Neurosci. 22, 3206–3214 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Jensen, J. et al. Direct activation of the ventral striatum in anticipation of aversive stimuli. Neuron 40, 1251–1257 (2003).

    Article  CAS  PubMed  Google Scholar 

  49. Hsieh, J. C., Stone-Elander, S. & Ingvar, M. Anticipatory coping of pain expressed in the human anterior cingulate cortex: a positron emission tomography study. Neurosci. Lett. 262, 61–64 (1999).

    Article  CAS  PubMed  Google Scholar 

  50. Ploghaus, A. et al. Dissociating pain from its anticipation in the human brain. Science 284, 1979–1981 (1999). This is the first study to examine the effect of pain anticipation on pain processing.

    Article  CAS  PubMed  Google Scholar 

  51. Sawamoto, N. et al. Expectation of pain enhances responses to nonpainful somatosensory stimulation in the anterior cingulate cortex and parietal operculum/posterior insula: an event-related functional magnetic resonance imaging study. J. Neurosci. 20, 7438–7445 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Lopez-Sola, M. et al. Dynamic assessment of the right lateral frontal cortex response to painful stimulation. Neuroimage 50, 1177–1187 (2010).

    Article  PubMed  Google Scholar 

  53. Fairhurst, M., Wiech, K., Dunckley, P. & Tracey, I. Anticipatory brainstem activity predicts neural processing of pain in humans. Pain 128, 101–110 (2007).

    Article  PubMed  Google Scholar 

  54. Beecher, H. K. Pain in men wounded in battle. Ann. Surg. 123, 96–105 (1946).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Morley, S. Efficacy and effectiveness of cognitive behaviour therapy for chronic pain: progress and some challenges. Pain 152, S99–S106 (2011).

    Article  PubMed  Google Scholar 

  56. Zeidan, F., Grant, J. A., Brown, C. A., McHaffie, J. G. & Coghill, R. C. Mindfulness meditation-related pain relief: evidence for unique brain mechanisms in the regulation of pain. Neurosci. Lett. 520, 165–173 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Jensen, K. B. et al. The use of functional neuroimaging to evaluate psychological and other non-pharmacological treatments for clinical pain. Neurosci. Lett. 520, 156–164 (2012).

    Article  CAS  PubMed  Google Scholar 

  58. Beydoun, A., Morrow, T. J., Shen, J. F. & Casey, K. L. Variability of laser-evoked potentials: attention, arousal and lateralized differences. Electroencephalogr. Clin. Neurophysiol. 88, 173–181 (1993).

    Article  CAS  PubMed  Google Scholar 

  59. Roy, M., Peretz, I. & Rainville, P. Emotional valence contributes to music-induced analgesia. Pain 134, 140–147 (2008).

    Article  PubMed  Google Scholar 

  60. Villemure, C., Slotnick, B. M. & Bushnell, M. C. Effects of odors on pain perception: deciphering the roles of emotion and attention. Pain 106, 101–108 (2003).

    Article  PubMed  Google Scholar 

  61. Loggia, M. L., Mogil, J. S. & Bushnell, M. C. Experimentally induced mood changes preferentially affect pain unpleasantness. J. Pain 9, 784–791 (2008).

    Article  PubMed  Google Scholar 

  62. Roy, M., Lebuis, A., Peretz, I. & Rainville, P. The modulation of pain by attention and emotion: a dissociation of perceptual and spinal nociceptive processes. Eur. J. Pain 15, 641–610 (2011).

    PubMed  Google Scholar 

  63. Bushnell, M. C. et al. Pain perception: is there a role for primary somatosensory cortex? Proc. Natl Acad. Sci. USA 96, 7705–7709 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Longe, S. E. et al. Counter-stimulatory effects on pain perception and processing are significantly altered by attention: an fMRI study. Neuroreport 12, 2021–2025 (2001).

    Article  CAS  PubMed  Google Scholar 

  65. Bantick, S. J. et al. Imaging how attention modulates pain in humans using functional MRI. Brain 125, 310–319 (2002).

    Article  PubMed  Google Scholar 

  66. Brooks, J. C., Nurmikko, T. J., Bimson, W. E., Singh, K. D. & Roberts, N. fMRI of thermal pain: effects of stimulus laterality and attention. Neuroimage 15, 293–301 (2002).

    Article  PubMed  Google Scholar 

  67. Valet, M. et al. Distraction modulates connectivity of the cingulo–frontal cortex and the midbrain during pain — an fMRI analysis. Pain 109, 399–408 (2004).

    Article  PubMed  Google Scholar 

  68. Wiech, K. et al. Modulation of pain processing in hyperalgesia by cognitive demand. Neuroimage 27, 59–69 (2005).

    Article  PubMed  Google Scholar 

  69. Ploner, M., Lee, M. C., Wiech, K., Bingel, U. & Tracey, I. Flexible cerebral connectivity patterns subserve contextual modulations of pain. Cereb. Cortex 21, 719–726 (2011).

    Article  PubMed  Google Scholar 

  70. Dunckley, P. et al. Attentional modulation of visceral and somatic pain. Neurogastroenterol. Motil. 19, 569–577 (2007).

    Article  CAS  PubMed  Google Scholar 

  71. Phillips, M. L. et al. The effect of negative emotional context on neural and behavioural responses to oesophageal stimulation. Brain 126, 669–684 (2003).

    Article  PubMed  Google Scholar 

  72. Roy, M., Piche, M., Chen, J. I., Peretz, I. & Rainville, P. Cerebral and spinal modulation of pain by emotions. Proc. Natl Acad. Sci. USA 106, 20900–20905 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Berna, C. et al. Induction of depressed mood disrupts emotion regulation neurocircuitry and enhances pain unpleasantness. Biol. Psychiatry 1083–1090 (2010).

    Article  PubMed  Google Scholar 

  74. Basbaum, A. I. & Fields, H. L. Endogenous pain control mechanisms: review and hypothesis. Ann. Neurol. 4, 451–462 (1978). This article provides the first complete analysis of descending pain modulatory circuits.

    Article  CAS  PubMed  Google Scholar 

  75. Ossipov, M. H., Dussor, G. O. & Porreca, F. Central modulation of pain. J. Clin. Invest. 120, 3779–3787 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Petrovic, P., Petersson, K. M., Ghatan, P. H., Stone-Elander, S. & Ingvar, M. Pain-related cerebral activation is altered by a distracting cognitive task. Pain 85, 19–30 (2000).

    Article  CAS  PubMed  Google Scholar 

  77. Frankenstein, U. N., Richter, W., McIntyre, M. C. & Remy, F. Distraction modulates anterior cingulate gyrus activations during the cold pressor test. Neuroimage 14, 827–836 (2001).

    Article  CAS  PubMed  Google Scholar 

  78. Tracey, I. et al. Imaging attentional modulation of pain in the periaqueductal gray in humans. J. Neurosci. 22, 2748–2752 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Corbetta, M. & Shulman, G. L. Control of goal-directed and stimulus-driven attention in the brain. Nature Rev. Neurosci. 3, 201–215 (2002).

    Article  CAS  Google Scholar 

  80. Cavada, C. & Goldman-Rakic, P. S. Posterior parietal cortex in rhesus monkey: I. Parcellation of areas based on distinctive limbic and sensory corticocortical connections. J. Comp. Neurol. 287, 393–421 (1989).

    Article  CAS  PubMed  Google Scholar 

  81. Cavada, C. & Goldman-Rakic, P. S. Posterior parietal cortex in rhesus monkey: II. Evidence for segregated corticocortical networks linking sensory and limbic areas with the frontal lobe. J. Comp. Neurol. 287, 422–445 (1989).

    Article  CAS  PubMed  Google Scholar 

  82. Prevosto, V., Graf, W. & Ugolini, G. Proprioceptive pathways to posterior parietal areas MIP and LIPv from the dorsal column nuclei and the postcentral somatosensory cortex. Eur. J. Neurosci. 33, 444–460 (2011).

    Article  PubMed  Google Scholar 

  83. Eippert, F. et al. Activation of the opioidergic descending pain control system underlies placebo analgesia. Neuron 63, 533–543 (2009).

    Article  CAS  PubMed  Google Scholar 

  84. Wager, T. D. et al. Placebo-induced changes in fMRI in the anticipation and experience of pain. Science 303, 1162–1167 (2004). This study identifies the neural circuitry underlying placebo analgesia.

    Article  CAS  PubMed  Google Scholar 

  85. Wager, T. D., Scott, D. J. & Zubieta, J. K. Placebo effects on human μ-opioid activity during pain. Proc. Natl Acad. Sci. USA 104, 11056–11061 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Amanzio, M. & Benedetti, F. Neuropharmacological dissection of placebo analgesia: expectation-activated opioid systems versus conditioning-activated specific subsystems. J. Neurosci. 19, 484–494 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Zhang, R.-R., Zhang, W.-C., Wang, J.-Y. & Guo, J.-Y. The opioid placebo analgesia is mediated exclusively through μ-opioid receptor in rat. Int. J. Neuropsychopharmacol. 16, 849–856 (2013).

    Article  CAS  PubMed  Google Scholar 

  88. Guo, J. Y., Wang, J. Y. & Luo, F. Dissection of placebo analgesia in mice: the conditions for activation of opioid and non-opioid systems. J. Psychopharmacol. 24, 1561–1567 (2010).

    Article  CAS  PubMed  Google Scholar 

  89. Buhle, J. T., Stevens, B. L., Friedman, J. J. & Wager, T. D. Distraction and placebo: two separate routes to pain control. Psychol. Sci. 23, 246–253 (2012).

    Article  PubMed  Google Scholar 

  90. Derbyshire, S. W. et al. Cerebral responses to noxious thermal stimulation in chronic low back pain patients and normal controls. Neuroimage 16, 158–168 (2002).

    Article  CAS  PubMed  Google Scholar 

  91. Gracely, R. H., Petzke, F., Wolf, J. M. & Clauw, D. J. Functional magnetic resonance imaging evidence of augmented pain processing in fibromyalgia. Arthritis Rheum. 46, 1333–1343 (2002). This paper demonstrates enhanced pain processing in patients with chronic pain.

    Article  PubMed  Google Scholar 

  92. Lawal, A., Kern, M., Sidhu, H., Hofmann, C. & Shaker, R. Novel evidence for hypersensitivity of visceral sensory neural circuitry in irritable bowel syndrome patients. Gastroenterology 130, 26–33 (2006).

    Article  PubMed  Google Scholar 

  93. Naliboff, B. D. et al. Cerebral activation in patients with irritable bowel syndrome and control subjects during rectosigmoid stimulation. Psychosom. Med. 63, 365–375 (2001).

    Article  CAS  PubMed  Google Scholar 

  94. Pukall, C. F. et al. Neural correlates of painful genital touch in women with vulvar vestibulitis syndrome. Pain 115, 118–127 (2005).

    Article  PubMed  Google Scholar 

  95. Gwilym, S. E. et al. Psychophysical and functional imaging evidence supporting the presence of central sensitization in a cohort of osteoarthritis patients. Arthritis Rheum. 61, 1226–1234 (2009).

    Article  PubMed  Google Scholar 

  96. Porreca, F., Ossipov, M. H. & Gebhart, G. F. Chronic pain and medullary descending facilitation. Trends Neurosci. 25, 319–325 (2002).

    Article  CAS  PubMed  Google Scholar 

  97. Le Bars, D. The whole body receptive field of dorsal horn multireceptive neurones. Brain Res. Brain Res. Rev. 40, 29–44 (2002).

    Article  PubMed  Google Scholar 

  98. Sprenger, C., Bingel, U. & Buchel, C. Treating pain with pain: supraspinal mechanisms of endogenous analgesia elicited by heterotopic noxious conditioning stimulation. Pain 152, 428–439 (2011).

    Article  PubMed  Google Scholar 

  99. Lewis, G. N., Rice, D. A. & McNair, P. J. Conditioned pain modulation in populations with chronic pain: a systematic review and meta-analysis. J. Pain 13, 936–944 (2012).

    Article  PubMed  Google Scholar 

  100. Jensen, K. B. et al. Evidence of dysfunctional pain inhibition in Fibromyalgia reflected in rACC during provoked pain. Pain 144, 95–100 (2009).

    Article  PubMed  Google Scholar 

  101. Burgmer, M. et al. Fibromyalgia unique temporal brain activation during experimental pain: a controlled fMRI study. J. Neural Transm. 117, 123–131 (2010).

    Article  PubMed  Google Scholar 

  102. Berman, S. M. et al. Reduced brainstem inhibition during anticipated pelvic visceral pain correlates with enhanced brain response to the visceral stimulus in women with irritable bowel syndrome. J. Neurosci. 28, 349–359 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Baliki, M. N. et al. Chronic pain and the emotional brain: specific brain activity associated with spontaneous fluctuations of intensity of chronic back pain. J. Neurosci. 26, 12165–12173 (2006). This study shows that chronic pain activates unique patterns of cortical activity.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Seminowicz, D. A. et al. Effective treatment of chronic low back pain in humans reverses abnormal brain anatomy and function. J. Neurosci. 31, 7540–7550 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Schmidt-Wilcke, T. et al. Affective components and intensity of pain correlate with structural differences in gray matter in chronic back pain patients. Pain 125, 89–97 (2006).

    Article  CAS  PubMed  Google Scholar 

  106. Apkarian, A. V. et al. Chronic back pain is associated with decreased prefrontal and thalamic gray matter density. J. Neurosci. 24, 10410–10415 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Davis, K. D. & Moayedi, M. Central mechanisms of pain revealed through functional and structural MRI. J. Neuroimmune Pharmacol. 24 Jul 2012 (doi:10.1007/s11481-012-9386-8).

    Article  PubMed  Google Scholar 

  108. Geha, P. Y. et al. The brain in chronic CRPS pain: abnormal gray–white matter interactions in emotional and autonomic regions. Neuron 60, 570–581 (2008). This study links chronic pain with both grey and white matter changes.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Lutz, J. et al. White and gray matter abnormalities in the brain of patients with fibromyalgia: a diffusion-tensor and volumetric imaging study. Arthritis Rheum. 58, 3960–3969 (2008).

    Article  PubMed  Google Scholar 

  110. Sundgren, P. C. et al. Diffusion-weighted and diffusion tensor imaging in fibromyalgia patients: a prospective study of whole brain diffusivity, apparent diffusion coefficient, and fraction anisotropy in different regions of the brain and correlation with symptom severity. Acad. Radiol. 14, 839–846 (2007).

    Article  PubMed  Google Scholar 

  111. Gerstner, G., Ichesco, E., Quintero, A. & Schmidt-Wilcke, T. Changes in regional gray and white matter volume in patients with myofascial-type temporomandibular disorders: a voxel-based morphometry study. J. Orofac. Pain 25, 99–106 (2011).

    PubMed  Google Scholar 

  112. Granziera, C., DaSilva, A. F., Snyder, J., Tuch, D. S. & Hadjikhani, N. Anatomical alterations of the visual motion processing network in migraine with and without aura. PLoS. Med. 3, e402 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

  113. Szabo, N. et al. White matter microstructural alterations in migraine: a diffusion-weighted MRI study. Pain 153, 651–656 (2012).

    Article  PubMed  Google Scholar 

  114. Moayedi, M. et al. White matter brain and trigeminal nerve abnormalities in temporomandibular disorder. Pain 153, 1467–1477 (2012).

    Article  PubMed  Google Scholar 

  115. McEwen, B. S. The neurobiology of stress: from serendipity to clinical relevance. Brain Res. 886, 172–189 (2000).

    Article  CAS  PubMed  Google Scholar 

  116. Apkarian, A. V. et al. Expression of IL-1β in supraspinal brain regions in rats with neuropathic pain. Neurosci. Lett. 407, 176–181 (2006).

    Article  PubMed  CAS  Google Scholar 

  117. Norman, G. J. et al. Stress and IL-1β contribute to the development of depressive-like behavior following peripheral nerve injury. Mol. Psychiatry 15, 404–414 (2010).

    Article  CAS  PubMed  Google Scholar 

  118. Xu, H. et al. Presynaptic and postsynaptic amplifications of neuropathic pain in the anterior cingulate cortex. J. Neurosci. 28, 7445–7453 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Metz, A. E., Yau, H. J., Centeno, M. V., Apkarian, A. V. & Martina, M. Morphological and functional reorganization of rat medial prefrontal cortex in neuropathic pain. Proc. Natl Acad. Sci. USA 106, 2423–2428 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Grachev, I. D., Fredrickson, B. E. & Apkarian, A. V. Brain chemistry reflects dual states of pain and anxiety in chronic low back pain. J. Neural Transm. 109, 1309–1334 (2002).

    Article  CAS  PubMed  Google Scholar 

  121. Harris, R. E. et al. Dynamic levels of glutamate within the insula are associated with improvements in multiple pain domains in fibromyalgia. Arthritis Rheum. 58, 903–907 (2008).

    Article  CAS  PubMed  Google Scholar 

  122. Grachev, I. D., Fredrickson, B. E. & Apkarian, A. V. Abnormal brain chemistry in chronic back pain: an in vivo proton magnetic resonance spectroscopy study. Pain 89, 7–18 (2000).

    Article  CAS  PubMed  Google Scholar 

  123. Harris, R. E. et al. Elevated insular glutamate in fibromyalgia is associated with experimental pain. Arthritis Rheum. 60, 3146–3152 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Gussew, A., Rzanny, R., Gullmar, D., Scholle, H. C. & Reichenbach, J. R. 1H-MR spectroscopic detection of metabolic changes in pain processing brain regions in the presence of non-specific chronic low back pain. Neuroimage 54, 1315–1323 (2011).

    Article  PubMed  Google Scholar 

  125. Mhalla, A., de Andrade, D. C., Baudic, S., Perrot, S. & Bouhassira, D. Alteration of cortical excitability in patients with fibromyalgia. Pain 149, 495–500 (2010).

    Article  PubMed  Google Scholar 

  126. Harris, R. E. et al. Decreased central μ-opioid receptor availability in fibromyalgia. J. Neurosci. 27, 10000–10006 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Jones, A. K. P. et al. Changes in central opioid receptor binding in relation to inflammation and pain in patients with rheumatoid arthritis. Br. J. Rheumatol. 33, 909–916 (1994).

    Article  CAS  PubMed  Google Scholar 

  128. Jones, A. K., Watabe, H., Cunningham, V. J. & Jones, T. Cerebral decreases in opioid receptor binding in patients with central neuropathic pain measured by [11C]diprenorphine binding and PET. Eur. J. Pain 8, 479–485 (2004).

    Article  CAS  PubMed  Google Scholar 

  129. Maarrawi, J. et al. Differential brain opioid receptor availability in central and peripheral neuropathic pain. Pain 127, 183–194 (2007).

    Article  CAS  PubMed  Google Scholar 

  130. Wood, P. B. et al. Fibromyalgia patients show an abnormal dopamine response to pain. Eur. J. Neurosci. 25, 3576–3582 (2007).

    Article  PubMed  Google Scholar 

  131. Narita, M. et al. Chronic pain induces anxiety with concomitant changes in opioidergic function in the amygdala. Neuropsychopharmacology 31, 739–750 (2006).

    Article  CAS  PubMed  Google Scholar 

  132. Narita, M. et al. Chronic pain-induced emotional dysfunction is associated with astrogliosis due to cortical δ-opioid receptor dysfunction. J. Neurochem. 97, 1369–1378 (2006).

    Article  CAS  PubMed  Google Scholar 

  133. Moriarty, O., McGuire, B. E. & Finn, D. P. The effect of pain on cognitive function: a review of clinical and preclinical research. Prog. Neurobiol. 93, 385–404 (2011).

    Article  PubMed  Google Scholar 

  134. Leavitt, F. & Katz, R. S. Distraction as a key determinant of impaired memory in patients with fibromyalgia. J. Rheumatol. 33, 127–132 (2006).

    PubMed  Google Scholar 

  135. Dick, B. D., Verrier, M. J., Harker, K. T. & Rashiq, S. Disruption of cognitive function in Fibromyalgia Syndrome. Pain 139, 610–616 (2008).

    Article  PubMed  Google Scholar 

  136. Munguia-Izquierdo, D. & Legaz-Arrese, A. Assessment of the effects of aquatic therapy on global symptomatology in patients with fibromyalgia syndrome: a randomized controlled trial. Arch. Phys. Med. Rehabil. 89, 2250–2257 (2008).

    Article  PubMed  Google Scholar 

  137. Verdejo-Garcia, A., Lopez-Torrecillas, F., Calandre, E. P., Delgado-Rodriguez, A. & Bechara, A. Executive function and decision-making in women with fibromyalgia. Arch. Clin. Neuropsychol. 24, 113–122 (2009).

    Article  PubMed  Google Scholar 

  138. Walteros, C. et al. Altered associative learning and emotional decision making in fibromyalgia. J. Psychosom. Res. 70, 294–301 (2011).

    Article  PubMed  Google Scholar 

  139. Apkarian, A. V. et al. Chronic pain patients are impaired on an emotional decision-making task. Pain 108, 129–136 (2004).

    Article  PubMed  Google Scholar 

  140. Pais-Vieira, M., Mendes-Pinto, M. M., Lima, D. & Galhardo, V. Cognitive impairment of prefrontal-dependent decision-making in rats after the onset of chronic pain. Neuroscience 161, 671–679 (2009).

    Article  CAS  PubMed  Google Scholar 

  141. Hattori, N. et al. Differential SPECT activation patterns associated with PASAT performance may indicate frontocerebellar functional dissociation in chronic mild traumatic brain injury. J. Nucl. Med. 50, 1054–1061 (2009).

    Article  PubMed  Google Scholar 

  142. Yu, H. J. et al. Multiple white matter tract abnormalities underlie cognitive impairment in RRMS. Neuroimage 59, 3713–3722 (2012).

    Article  PubMed  Google Scholar 

  143. Sigurdardottir, S., Jerstad, T., Andelic, N., Roe, C. & Schanke, A. K. Olfactory dysfunction, gambling task performance and intracranial lesions after traumatic brain injury. Neuropsychology 24, 504–513 (2010).

    Article  PubMed  Google Scholar 

  144. van Noordt, S. & Good, D. Mild head injury and sympathetic arousal: investigating relationships with decision-making and neuropsychological performance in university students. Brain Inj. 25, 707–716 (2011).

    Article  PubMed  Google Scholar 

  145. Roca, M. et al. Cognitive deficits in multiple sclerosis correlate with changes in fronto-subcortical tracts. Mult. Scler. 14, 364–369 (2008).

    Article  CAS  PubMed  Google Scholar 

  146. Owen, A. M., McMillan, K. M., Laird, A. R. & Bullmore, E. N-back working memory paradigm: a meta-analysis of normative functional neuroimaging studies. Hum. Brain Mapp. 25, 46–59 (2005).

    Article  PubMed  PubMed Central  Google Scholar 

  147. Bechara, A., Damasio, H. & Damasio, A. R. Emotion, decision making and the orbitofrontal cortex. Cereb. Cortex 10, 295–307 (2000).

    Article  CAS  PubMed  Google Scholar 

  148. Elsenbruch, S. et al. Patients with irritable bowel syndrome have altered emotional modulation of neural responses to visceral stimuli. Gastroenterology 139, 1310–1319 (2010).

    Article  PubMed  Google Scholar 

  149. Tiemann, L. et al. Behavioral and neuronal investigations of hypervigilance in patients with fibromyalgia syndrome. PLoS ONE 7, e35068 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Arnold, B. S. et al. Affective pain modulation in fibromyalgia, somatoform pain disorder, back pain, and healthy controls. Eur. J. Pain 12, 329–338 (2008).

    Article  PubMed  Google Scholar 

  151. Snijders, T. J., Ramsey, N. F., Koerselman, F. & van Gijn, J. Attentional modulation fails to attenuate the subjective pain experience in chronic, unexplained pain. Eur. J. Pain 14, 282.e1–282.e10 (2010).

    Article  CAS  Google Scholar 

  152. Montoya, P., Pauli, P., Batra, A. & Wiedemann, G. Altered processing of pain-related information in patients with fibromyalgia. Eur. J. Pain 9, 293–303 (2005).

    Article  PubMed  Google Scholar 

  153. Vase, L., Robinson, M. E., Verne, G. N. & Price, D. D. Increased placebo analgesia over time in irritable bowel syndrome (IBS) patients is associated with desire and expectation but not endogenous opioid mechanisms. Pain 115, 338–347 (2005).

    Article  PubMed  Google Scholar 

  154. Obermann, M. et al. Gray matter changes related to chronic posttraumatic headache. Neurology 73, 978–983 (2009).

    Article  PubMed  Google Scholar 

  155. Rodriguez-Raecke, R., Niemeier, A., Ihle, K., Ruether, W. & May, A. Brain gray matter decrease in chronic pain is the consequence and not the cause of pain. J. Neurosci. 29, 13746–13750 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Gwilym, S. E., Filippini, N., Douaud, G., Carr, A. J. & Tracey, I. Thalamic atrophy associated with painful osteoarthritis of the hip is reversible after arthroplasty: a longitudinal voxel-based morphometric study. Arthritis Rheum. 62, 2930–2940 (2010).

    Article  PubMed  Google Scholar 

  157. Zhao, M. G., Toyoda, H., Wang, Y. K. & Zhuo, M. Enhanced synaptic long-term potentiation in the anterior cingulate cortex of adult wild mice as compared with that in laboratory mice. Mol. Brain 2, 11 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  158. Ikeda, H., Tsuda, M., Inoue, K. & Murase, K. Long-term potentiation of neuronal excitation by neuron-glia interactions in the rat spinal dorsal horn. Eur. J. Neurosci. 25, 1297–1306 (2007).

    Article  PubMed  Google Scholar 

  159. Jensen, K. B. et al. Cognitive Behavioral Therapy increases pain-evoked activation of the prefrontal cortex in patients with fibromyalgia. Pain 153, 1495–1503 (2012).

    Article  PubMed  Google Scholar 

  160. Grant, J. A., Courtemanche, J. & Rainville, P. A non-elaborative mental stance and decoupling of executive and pain-related cortices predicts low pain sensitivity in Zen meditators. Pain 152, 150–156 (2011).

    Article  PubMed  Google Scholar 

  161. Gard, T. et al. Pain attenuation through mindfulness is associated with decreased cognitive control and increased sensory processing in the brain. Cereb. Cortex 22, 2692–2702 (2012).

    Article  PubMed  Google Scholar 

  162. Zeidan, F. et al. Brain mechanisms supporting the modulation of pain by mindfulness meditation. J. Neurosci. 31, 5540–5548 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  163. Lazar, S. W. et al. Meditation experience is associated with increased cortical thickness. Neuroreport 16, 1893–1897 (2005).

    Article  PubMed  PubMed Central  Google Scholar 

  164. Holzel, B. K. et al. Investigation of mindfulness meditation practitioners with voxel-based morphometry. Soc. Cogn. Affect. Neurosci. 3, 55–61 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  165. Luders, E., Toga, A. W., Lepore, N. & Gaser, C. The underlying anatomical correlates of long-term meditation: larger hippocampal and frontal volumes of gray matter. Neuroimage 45, 672–678 (2009).

    Article  PubMed  Google Scholar 

  166. Pessoa, L. On the relationship between emotion and cognition. Nature Rev. Neurosci. 9, 148–158 (2008).

    Article  CAS  Google Scholar 

  167. Seminowicz, D. A. et al. MRI structural brain changes associated with sensory and emotional function in a rat model of long-term neuropathic pain. Neuroimage 47, 1007–1014 (2009).

    Article  PubMed  Google Scholar 

  168. Low, L. A. et al. Nerve injury causes long-term attentional deficits in rats. Neurosci. Lett. 529, 103–107 (2012).

    Article  CAS  PubMed  Google Scholar 

  169. deCharms, R. C. et al. Control over brain activation and pain learned by using real-time functional MRI. Proc. Natl Acad. Sci. USA 102, 18626–18631 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  170. Yoo, S. S. et al. Brain–computer interface using fMRI: spatial navigation by thoughts. Neuroreport 15, 1591–1595 (2004).

    Article  PubMed  Google Scholar 

  171. van Praag, H., Kempermann, G. & Gage, F. H. Neural consequences of enviromental enrichment. Nature Rev. Neurosci. 1, 191–198 (2000).

    Article  CAS  Google Scholar 

  172. Gabriel, A. F. et al. Enriched environment and the recovery from inflammatory pain: social versus physical aspects and their interaction. Behav. Brain Res. 208, 90–95 (2010).

    Article  PubMed  Google Scholar 

  173. Gabriel, A. F., Marcus, M. A. E., Honig, W. M. M. & Joosten, E. A. J. Preoperative housing in an enriched environment significantly reduces the duration of post-operative pain in a rat model of knee inflammation. Neurosci. Lett. 469, 219–223 (2010).

    Article  CAS  PubMed  Google Scholar 

  174. Gabriel, A. F., Marcus, M. A., Honig, W. M., Helgers, N. & Joosten, E. A. Environmental housing affects the duration of mechanical allodynia and the spinal astroglial activation in a rat model of chronic inflammatory pain. Brain Res. 1276, 83–90 (2009).

    Article  CAS  PubMed  Google Scholar 

  175. Abramov, U., Kurrikoff, K., Matsui, T. & Vasar, E. Environmental enrichment reduces mechanical hypersensitivity in neuropathic mice, but fails to abolish the phenotype of CCK2 receptor deficient mice. Neurosci. Lett. 467, 230–233 (2009).

    Article  CAS  PubMed  Google Scholar 

  176. Shum, F. W. et al. Alteration of cingulate long-term plasticity and behavioral sensitization to inflammation by environmental enrichment. Learn. Mem. 14, 304–312 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  177. Stagg, N. J. et al. Regular exercise reverses sensory hypersensitivity in a rat neuropathic pain model: role of endogenous opioids. Anesthesiology 114, 940–948 (2011).

    Article  CAS  PubMed  Google Scholar 

  178. Bakos, J. et al. Oxytocin levels in the posterior pituitary and in the heart are modified by voluntary wheel running. Regul. Pept. 139, 96–101 (2007).

    Article  CAS  PubMed  Google Scholar 

  179. Boyette-Davis, J. A., Thompson, C. D. & Fuchs, P. N. Alterations in attentional mechanisms in response to acute inflammatory pain and morphine administration. Neuroscience 151, 558–563 (2008).

    Article  CAS  PubMed  Google Scholar 

  180. Ford, G. K., Moriarty, O., McGuire, B. E. & Finn, D. P. Investigating the effects of distracting stimuli on nociceptive behaviour and associated alterations in brain monoamines in rats. Eur. J. Pain 12, 970–979 (2008).

    Article  PubMed  Google Scholar 

  181. Ji, G. et al. Cognitive impairment in pain through amygdala-driven prefrontal cortical deactivation. J. Neurosci. 30, 5451–5464 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  182. Leite-Almeida, H. et al. The impact of age on emotional and cognitive behaviours triggered by experimental neuropathy in rats. Pain 144, 57–65 (2009).

    Article  PubMed  Google Scholar 

  183. Hu, Y., Yang, J., Hu, Y., Wang, Y. & Li, W. Amitriptyline rather than lornoxicam ameliorates neuropathic pain-induced deficits in abilities of spatial learning and memory. Eur. J. Anaesthesiol. 27, 162–168 (2010).

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

Preparation of this manuscript was supported by the Intramural Research Program of the US National Institutes of Health, National Center for Complementary and Alternative Medicine.

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Glossary

Descending pain modulatory systems

Networks in the brain involving pathways from the cerebral cortex down to the spinal cord that can lead to inhibition or excitation of afferent pain signals at multiple levels of the brain.

Fibromyalgia

A disorder in which there is widespread pain in all four quadrants of the body for a minimum duration of 3 months. Additionally, at least 11 of 18 specified points on the neck, shoulder, chest, hip, knee and elbow regions show tenderness to pressure.

Vulvar vestibulitis

A disorder characterized by sensitivity around the vaginal orifice, with pain provoked by contact or pressure.

Ascending nociceptive pathways

Fibres travelling to the brain from receptors in body tissues that respond to tissue-damaging or potentially tissue-damaging stimuli (nociceptors). They make synapses with second-order neurons in the dorsal horn of the spinal cord, which send projections to the brainstem, thalamus or other brain regions. From there, third- and fourth-order neurons send projections to the cerebral cortex.

Complex regional pain syndrome

(CRPS). A chronic pain condition that can affect any part of the body but most frequently affects an arm or a leg. After what is often a minor injury, such as a sprained ankle, there is an intense burning pain that is much stronger than would be expected for the type of injury. The pain gets worse rather than better with time and is often accompanied by trophic changes, such as altered skin temperature and texture, faster growth of nails and hair and even loss of bone density.

Iowa gambling task

A psychological task used to investigate emotional decision-making. It involves playing with four card decks in order to win money. Playing with two of the decks leads to more wins than losses, whereas playing with the other decks leads to more losses than wins. Healthy people quickly gravitate to the 'good' decks. Patients with various types of frontal lobe lesions do not learn to preferentially use the 'good' decks.

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Bushnell, M., Čeko, M. & Low, L. Cognitive and emotional control of pain and its disruption in chronic pain. Nat Rev Neurosci 14, 502–511 (2013). https://doi.org/10.1038/nrn3516

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