Neuromodulatory treatments for chronic pain: efficacy and mechanisms

Key Points

  • Chronic pain is common and has substantial negative consequences for individuals and society

  • As the brain is ultimately the organ that processes pain information, treatments that target brain activity have the potential to provide pain relief

  • Solid evidence indicates that hypnosis has short-term and long-term benefits for a variety of pain problems, and should be considered as a first-line treatment given its demonstrated efficacy and positive side-effect profile

  • Training in meditation shows promise for reducing chronic pain, although more research is needed to confirm the initial findings

  • Noninvasive brain stimulation is potentially effective for reducing chronic pain in the short term, but preliminary evidence suggests that brain stimulation alone might not have long-term benefits

  • Neurofeedback has some potential for reducing chronic pain, although the research findings suggest weak effects when this technique is used alone


Chronic pain is common, and the available treatments do not provide adequate relief for most patients. Neuromodulatory interventions that modify brain processes underlying the experience of pain have the potential to provide substantial relief for some of these patients. The purpose of this Review is to summarize the state of knowledge regarding the efficacy and mechanisms of noninvasive neuromodulatory treatments for chronic pain. The findings provide support for the efficacy and positive side-effect profile of hypnosis, and limited evidence for the potential efficacy of meditation training, noninvasive electrical stimulation procedures, and neurofeedback procedures. Mechanisms research indicates that hypnosis influences multiple neurophysiological processes involved in the experience of pain. Evidence also indicates that mindfulness meditation has both immediate and long-term effects on cortical structures and activity involved in attention, emotional responding and pain. Less is known about the mechanisms of other neuromodulatory treatments. On the basis of the data discussed in this Review, training in the use of self-hypnosis might be considered a viable 'first-line' approach to treat chronic pain. More-definitive research regarding the benefits and costs of meditation training, noninvasive brain stimulation and neurofeedback is needed before these treatments can be recommended for the treatment of chronic pain.

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Figure 1: Noninvasive brain stimulation and neurofeedback techniques for the treatment of chronic pain.


  1. 1

    Breivik, H., Collett, B., Ventafridda, V., Cohen, R. & Gallacher, D. Survey of chronic pain in Europe: prevalence, impact on daily life, and treatment. Eur. J. Pain 10, 287–333 (2006).

    Article  Google Scholar 

  2. 2

    Smith, B. H. & Torrance, N. Epidemiology of neuropathic pain and its impact on quality of life. Curr. Pain Headache Rep. 16, 191–198 (2012).

    Article  Google Scholar 

  3. 3

    Toth, C., Lander, J. & Wiebe, S. The prevalence and impact of chronic pain with neuropathic pain symptoms in the general population. Pain Med. 10, 918–929 (2009).

    Article  Google Scholar 

  4. 4

    Institute of Medicine. Relieving Pain in America: A Blueprint for Transforming Prevention, Care, Education, and Research (The National Academics Press, 2011).

  5. 5

    Huguet, A. & Miró, J. The severity of chronic pediatric pain: an epidemiological study. J. Pain 9, 226–236 (2008).

    Article  Google Scholar 

  6. 6

    Tsang, A. et al. Common chronic pain conditions in developed and developing countries: gender and age differences and comorbidity with depression–anxiety disorders. J. Pain 9, 883–891 (2008).

    Article  Google Scholar 

  7. 7

    Langley, P. C., Van Litsenburg, C., Cappelleri, J. C. & Carroll, D. The burden associated with neuropathic pain in Western Europe. J. Med. Econ. 16, 85–95 (2013).

    Article  Google Scholar 

  8. 8

    Vranken, J. H. Elucidation of pathophysiology and treatment of neuropathic pain. Cent. Nerv. Syst. Agents Med. Chem. 12, 304–314 (2012).

    Article  CAS  Google Scholar 

  9. 9

    Jefferies, K. Treatment of neuropathic pain. Semin. Neurol. 30, 425–432 (2010).

    Article  Google Scholar 

  10. 10

    Baron, R., Binder, A. & Wasner, G. Neuropathic pain: diagnosis, pathophysiological mechanisms, and treatment. Lancet Neurol. 9, 807–819 (2010).

    Article  Google Scholar 

  11. 11

    Furlan, A. D., Sandoval, J. A., Mailis-Gagnon, A. & Tunks, E. Opioids for chronic noncancer pain: a meta-analysis of effectiveness and side effects. CMAJ 174, 1589–1594 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

  12. 12

    Apkarian, A. V., Hashmi, J. A. & Baliki, M. N. Pain and the brain: specificity and plasticity of the brain in clinical chronic pain. Pain 152 (Suppl. 3), S49–S64 (2011).

    Article  Google Scholar 

  13. 13

    Jensen, M., Hakimian, S., Sherlin, L. H. & Fregni, F. New insights into neuromodulatory approaches for the treatment of pain. J. Pain 9, 193–199 (2008).

    Article  Google Scholar 

  14. 14

    Kihlstrom, J. F. Hypnosis. Annu. Rev. Psychol. 36, 385–418 (1985).

    Article  CAS  Google Scholar 

  15. 15

    Oakley, D. A. & Halligan, P. W. Hypnotic suggestion: opportunities for cognitive neuroscience. Nat. Rev. Neurosci. 14, 565–576 (2013).

    Article  CAS  Google Scholar 

  16. 16

    Derbyshire, S. W., Whalley, M. G. & Oakley, D. A. Fibromyalgia pain and its modulation by hypnotic and non-hypnotic suggestion: an fMRI analysis. Eur. J. Pain 13, 542–550 (2009).

    Article  Google Scholar 

  17. 17

    Derbyshire, S. W., Whalley, M. G., Stenger, V. A. & Oakley, D. A. Cerebral activation during hypnotically induced and imagined pain. Neuroimage 23, 392–401 (2004).

    Article  Google Scholar 

  18. 18

    Jensen, M. P. Hypnosis for Chronic Pain Management: Therapist Guide (Oxford University Press, 2011).

    Google Scholar 

  19. 19

    Jensen, M. & Patterson, D. R. Hypnotic treatment of chronic pain. J. Behav. Med. 29, 95–124 (2006).

    Article  Google Scholar 

  20. 20

    Patterson, D. R. & Jensen, M. P. Hypnosis and clinical pain. Psychol. Bull. 29, 495–521 (2003).

    Article  Google Scholar 

  21. 21

    Tome-Pires, C. & Miró, J. Hypnosis for the management of chronic and cancer procedure-related pain in children. Int. J. Clin. Exp. Hypn. 60, 432–457 (2012).

    Article  Google Scholar 

  22. 22

    Montgomery, G. H., DuHamel, K. N. & Redd, W. H. A meta-analysis of hypnotically induced analgesia: how effective is hypnosis? Int. J. Clin. Exp. Hypn. 48, 138–153 (2000).

    Article  CAS  Google Scholar 

  23. 23

    Dworkin, R. H. et al. Interpreting the clinical importance of group differences in chronic pain clinical trials: IMMPACT recommendations. Pain 146, 238–244 (2009).

    Article  Google Scholar 

  24. 24

    Jensen, M. P. et al. A comparison of self-hypnosis versus progressive muscle relaxation in patients with multiple sclerosis and chronic pain. Int. J. Clin. Exp. Hypn. 57, 198–221 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  25. 25

    Jensen, M. P. et al. Hypnotic analgesia for chronic pain in persons with disabilities: a case series. Int. J. Clin. Exp. Hypn. 53, 198–228 (2005).

    Article  Google Scholar 

  26. 26

    Jensen, M. P. et al. Effects of self-hypnosis training and EMG biofeedback relaxation training on chronic pain in persons with spinal-cord injury. Int. J. Clin. Exp. Hypn. 57, 239–268 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  27. 27

    Dworkin, R. H. et al. Interpreting the clinical importance of treatment outcomes in chronic pain clinical trials: IMMPACT recommendations. J. Pain 9, 105–121 (2008).

    Article  Google Scholar 

  28. 28

    Hilgard, E. & Hilgard, J. Hypnosis in the Relief of Pain 2nd edn (William Kaufmam, 1975).

    Google Scholar 

  29. 29

    Crawford, H. J., Kitner-Triolo, M., Clarke, S. W. & Olesko, B. Transient positive and negative experiences accompanying stage hypnosis. J. Abnorm. Psychol. 101, 663–667 (1992).

    Article  CAS  Google Scholar 

  30. 30

    Hammond, D. C. Review of the efficacy of clinical hypnosis with headaches and migraines. Int. J. Clin. Exp. Hypn. 55, 207–219 (2007).

    Article  Google Scholar 

  31. 31

    Crasilneck, H. B. Hypnosis in the control of chronic low back pain. Am. J. Clin. Hypn. 22, 71–78 (1979).

    Article  CAS  Google Scholar 

  32. 32

    Crawford, H. J. et al. Hypnotic analgesia: 1. Somatosensory event-related potential changes to noxious stimuli and 2. Transfer learning to reduce chronic low back pain. Int. J. Clin. Exp. Hypn. 46, 93–132 (1998).

    Article  Google Scholar 

  33. 33

    Jack, M. A. The use of hypnosis for a patient with chronic pain. Contemp. Hypn. 16, 231–237 (1999).

    Article  Google Scholar 

  34. 34

    Melzack, R. & Perry, C. Self-regulation of pain: the use of alpha-feedback and hypnotic training for the control of chronic pain. Exp. Neurol. 46, 452–469 (1975).

    Article  CAS  Google Scholar 

  35. 35

    Sachs, L. B., Feuerstein, M. & Vitale, J. H. Hypnotic self-regulation of chronic pain. Am. J. Clin. Hypn. 20, 106–113 (1977).

    Article  CAS  Google Scholar 

  36. 36

    Mott, T. Jr. Untoward effects associated with hypnosis. Psychiatr. Med. 10, 119–128 (1992).

    PubMed  Google Scholar 

  37. 37

    Stewart, J. H. Hypnosis in contemporary medicine. Mayo Clin. Proc. 80, 511–524 (2005).

    Article  Google Scholar 

  38. 38

    Jensen, M. P. et al. Satisfaction with, and the beneficial side effects of, hypnotic analgesia. Int. J. Clin. Exp. Hypn. 54, 432–447 (2006).

    Article  Google Scholar 

  39. 39

    De Benedittis, G. Understanding the multidimensional mechanisms of hypnotic analgesia. Contemp. Hypn. 20, 59–80 (2003).

    Article  Google Scholar 

  40. 40

    Jensen, M. P. The neurophysiology of pain perception and hypnotic analgesia: implications for clinical practice. Am. J. Clin. Hypn. 51, 123–148 (2008).

    Article  Google Scholar 

  41. 41

    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).

    Article  CAS  Google Scholar 

  42. 42

    Hofbauer, R. K., Rainville, P., Duncan, G. H. & Bushnell, M. C. Cortical representation of the sensory dimension of pain. J. Neurophysiol. 86, 402–411 (2001).

    Article  CAS  Google Scholar 

  43. 43

    Oakley, D. A., Deeley, Q. & Halligan, P. W. Hypnotic depth and response to suggestion under standardized conditions and during fMRI scanning. Int. J. Clin. Exp. Hypn. 55, 32–58 (2007).

    Article  Google Scholar 

  44. 44

    Gruzelier, J. H. Frontal functions, connectivity and neural efficiency underpinning hypnosis and hypnotic susceptibility. Contemp. Hypn. 23, 15–32 (2006).

    Article  Google Scholar 

  45. 45

    Chapman, L. F., Goodell, H. & Wolff, H. G. Changes in tissue vulnerability induced during hypnotic suggestion. J. Psychosom. Res. 4, 99–105 (1959).

    Article  CAS  Google Scholar 

  46. 46

    Hammond, D. C., Keye, W. R. & Grant, C. W. Jr. Hypnotic analgesia with burns: an initial study. Am. J. Clin. Hypn. 26, 56–59 (1983).

    Article  CAS  Google Scholar 

  47. 47

    Kiernan, B. D., Dane, J. R., Phillips, L. H. & Price, D. D. Hypnotic analgesia reduces R-III nociceptive reflex: further evidence concerning the multifactorial nature of hypnotic analgesia. Pain 60, 39–47 (1995).

    Article  CAS  Google Scholar 

  48. 48

    Danziger, N. et al. Different strategies of modulation can be operative during hypnotic analgesia: a neurophysiological study. Pain 75, 85–92 (1998).

    Article  CAS  Google Scholar 

  49. 49

    Crawford, H. J., Knebel, T. & Vendemia, J. The nature of hypnotic analgesia: neurophysiological foundation and evidence. Contemp. Hypn. 15, 22–33 (1998).

    Article  Google Scholar 

  50. 50

    Fingelkurts, A. A., Kallio, S. & Revonsuo, A. Cortex functional connectivity as a neurophysiological correlate of hypnosis: an EEG case study. Neuropsychologia 45, 1452–1462 (2007).

    Article  Google Scholar 

  51. 51

    Faymonville, M. E. et al. Increased cerebral functional connectivity underlying the antinociceptive effects of hypnosis. Brain Res. Cogn. Brain Res. 17, 255–262 (2003).

    Article  Google Scholar 

  52. 52

    Wagstaff, G. F., David, D., Kirsch, I. & Lynn, S. J. in Handbook of Clinical Hypnosis (eds Lynn, S. J. et al.) 179–208 (American Psychological Association, 2010).

    Google Scholar 

  53. 53

    Sadler, P. & Woody, E. in Handbook of Clinical Hypnosis (eds Lynn, S. J. et al.) 151–178 (American Psychological Association, 2010).

    Google Scholar 

  54. 54

    Crawford, H. J. & Gruzelier, J. H. in Contemporary Hypnosis Research (eds Fromm, E. & Nash, M. R.) 227–266 (Guilford Press, 1992).

    Google Scholar 

  55. 55

    Gruzelier, J. A theory of alpha/theta neurofeedback, creative performance enhancement, long distance functional connectivity and psychological integration. Cogn. Process. 10 (Suppl. 1), S101–S109 (2009).

    Article  Google Scholar 

  56. 56

    Lutz, A., Slagter, H. A., Dunne, J. D. & Davidson, R. J. Attention regulation and monitoring in meditation. Trends Cogn. Sci. 12, 163–169 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  57. 57

    Grant, J. A. Meditative analgesia: the current state of the field. Ann. N. Y. Acad. Sci.

  58. 58

    Kabat-Zinn, J. Mindfulness-based interventions in context: past, present, and future. Clin. Psychol. (New York) 10, 144–156 (2003).

    Google Scholar 

  59. 59

    Shapiro, S. L. & Carlson, L. E. The Art and Science of Mindfulness: Integrating Mindfulness into Psychology and the Helping Professions (American Psychological Association, 2009).

    Google Scholar 

  60. 60

    Fjorback, L. O., Arendt, M., Ornbøl, E., Fink, P. & Walach, H. Mindfulness-based stress reduction and mindfulness-based cognitive therapy: a systematic review of randomized controlled trials. Acta Psychiatr. Scand. 124, 102–119 (2011).

    Article  CAS  Google Scholar 

  61. 61

    Grossman, P., Niemann, L., Schmidt, S. & Walach, H. Mindfulness-based stress reduction and health benefits. A meta-analysis. J. Psychosom. Res. 57, 35–43 (2004).

    Article  Google Scholar 

  62. 62

    Keng, S. L., Smoski, M. J. & Robins, C. J. Effects of mindfulness on psychological health: a review of empirical studies. Clin. Psychol. Rev. 31, 1041–1056 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  63. 63

    Teixeira, E. The effect of mindfulness meditation on painful diabetic peripheral neuropathy in adults older than 50 years. Holist. Nurs. Pract. 24, 277–283 (2010).

    Article  Google Scholar 

  64. 64

    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 

  65. 65

    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 

  66. 66

    Davidson, R. J. & Goleman, D. J. The role of attention in meditation and hypnosis: a psychobiological perspective on transformations of consciousness. Int. J. Clin. Exp. Hypn. 25, 291–308 (1977).

    Article  CAS  Google Scholar 

  67. 67

    Carmody, J. & Baer, R. A. Relationships between mindfulness practice and levels of mindfulness, medical and psychological symptoms and well-being in a mindfulness-based stress reduction program. J. Behav. Med. 31, 23–33 (2008).

    Article  Google Scholar 

  68. 68

    Garland, E. L. et al. Therapeutic mechanisms of a mindfulness-based treatment for IBS: effects on visceral sensitivity, catastrophizing, and affective processing of pain sensations. J. Behav. Med. 35, 591–602 (2012).

    Article  Google Scholar 

  69. 69

    Brown, C. A. & Jones, A. K. Meditation experience predicts less negative appraisal of≈pain: electrophysiological evidence for the involvement of anticipatory neural responses. Pain 150, 428–438 (2010).

    Article  Google Scholar 

  70. 70

    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  Google Scholar 

  71. 71

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

    Article  Google Scholar 

  72. 72

    Fell, J., Axmacher, N. & Haupt, S. From alpha to gamma: electrophysiological correlates of meditation-related states of consciousness. Med. Hypotheses 75, 218–224 (2010).

    Article  Google Scholar 

  73. 73

    Ives-Deliperi, V. L., Solms, M. & Meintjes, E. M. The neural substrates of mindfulness: an fMRI investigation. Soc. Neurosci. 6, 231–242 (2011).

    Article  Google Scholar 

  74. 74

    Craig, A. D. How do you feel—now? The anterior insula and human awareness. Nat. Rev. Neurosci. 10, 59–70 (2009).

    Article  CAS  Google Scholar 

  75. 75

    Critchley, H. D., Wiens, S., Rotshtein, P., Ohman, A. & Dolan, R. J. Neural systems supporting interoceptive awareness. Nat. Neurosci. 7, 189–195 (2004).

    Article  CAS  Google Scholar 

  76. 76

    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  PubMed Central  Google Scholar 

  77. 77

    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  Google Scholar 

  78. 78

    Rainville, P., Carrier, B., Hofbauer, R. K., Bushnell, M. C. & Duncan, G. H. Dissociation of sensory and affective dimensions of pain using hypnotic modulation. Pain 82, 159–171 (1999).

    Article  CAS  Google Scholar 

  79. 79

    May, A. Chronic pain may change the structure ofxthe brain. Pain 137, 7–15 (2008).

    Article  Google Scholar 

  80. 80

    Cahn, B. R. & Polich, J. Meditation states and traits: EEG, ERP, and neuroimaging studies. Psychol. Bull. 132, 180–211 (2006).

    Article  Google Scholar 

  81. 81

    Aftanas, L. I. & Golocheikine, S. A. Human anterior and frontal midline theta and lower alpha reflect emotionally positive state and internalized attention: high-resolution EEG investigation of meditation. Neurosci. Lett. 310, 57–60 (2001).

    Article  CAS  Google Scholar 

  82. 82

    Barnhofer, T. et al. Effects of meditation on frontal alpha-asymmetry in previously suicidal individuals. Neuroreport 18, 709–712 (2007).

    Article  Google Scholar 

  83. 83

    Chiesa, A. & Serretti, A. A systematic review of neurobiological and clinical features of mindfulness meditations. Psychol. Med. 40, 1239–1252 (2010).

    Article  CAS  Google Scholar 

  84. 84

    Davidson, R. J. et al. Alterations in brain and immune function produced by mindfulness meditation. Psychosom. Med. 65, 564–570 (2003).

    Article  Google Scholar 

  85. 85

    Davidson, R. J., Ekman, P., Saron, C. D., Senulis, J. A. & Friesen, W. V. Approach-withdrawal and cerebral asymmetry: emotional expression and brain physiology. I. J. Pers. Soc. Psychol. 58, 330–341 (1990).

    Article  CAS  Google Scholar 

  86. 86

    Plow, E. B., Pascual-Leone, A. & Machado, A. Brain stimulation in the treatment of chronic neuropathic and non-cancerous pain. J. Pain 13, 411–424 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  87. 87

    O'Connell, N. E., Wand, B. M., Marston, L., Spencer, S. & Desouza, L. H. Non-invasive brain stimulation techniques for chronic pain. A report of a Cochrane systematic review and meta-analysis. Eur. J. Phys. Rehabil. Med. 47, 309–326 (2011).

    CAS  PubMed  Google Scholar 

  88. 88

    Marlow, N. M., Bonilha, H. S. & Short, E. B. Efficacy of transcranial direct current stimulation and repetitive transcranial magnetic stimulation for treating fibromyalgia syndrome: a systematic review. Pain Pract. 13, 131–145 (2013).

    Article  Google Scholar 

  89. 89

    Medeiros, L. F. et al. Neurobiological effects of transcranial direct current stimulation: a review. Front. Psychiatry 3, 110 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  90. 90

    Moreno-Duarte, I. et al. Targeted therapies using electrical and magnetic neural stimulation for the treatment of chronic pain in spinal cord injury. Neuroimage 85, 1003–1013 (2013).

    Article  Google Scholar 

  91. 91

    Leung, A. et al. rTMS for suppressing neuropathic pain: a meta-analysis. J. Pain 10, 1205–1216 (2009).

    Article  Google Scholar 

  92. 92

    Lefaucheur, J. P. et al. Analgesic effects of repetitive transcranial magnetic stimulation of the motor cortex in neuropathic pain: influence of theta burst stimulation priming. Eur. J. Pain 16, 1403–1413 (2012).

    Article  Google Scholar 

  93. 93

    Wrigley, P. J. et al. Longstanding neuropathic pain after spinal cord injury is refractory to transcranial direct current stimulation: a randomized controlled trial. Pain 154, 2178–2184 (2013).

    Article  Google Scholar 

  94. 94

    Siebner, H. R. et al. Preconditioning of low-frequency repetitive transcranial magnetic stimulation with transcranial direct current stimulation: evidence for homeostatic plasticity in the human motor cortex. J. Neurosci. 24, 3379–3385 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. 95

    Priori, A., Hallett, M. & Rothwell, J. C. Repetitive transcranial magnetic stimulation or transcranial direct current stimulation? Brain Stimul. 2, 241–245 (2009).

    Article  Google Scholar 

  96. 96

    Jensen, M. P. et al. Effects of non-pharmacological pain treatments on brain states. Clin. Neurophysiol. 124, 2016–2024 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  97. 97

    Zaghi, S., Heine, N. & Fregni, F. Brain stimulation for the treatment of pain: a review of costs, clinical effects, and mechanisms of treatment for three different central neuromodulatory approaches. J. Pain Manag. 2, 339–352 (2009).

    PubMed  PubMed Central  Google Scholar 

  98. 98

    Jasper, H. H. The ten–twenty electrode system of the International Federation. Electroencephalogr. Clin. Neurophysiol. 10, 371–375 (1958).

    Google Scholar 

  99. 99

    Sime, A. Case study of trigeminal neuralgia using neurofeedback and peripheral biofeedback. J. Neurother. 8, 59–71 (2004).

    Article  Google Scholar 

  100. 100

    Caro, X. J. & Winter, E. F. EEG biofeedback treatment improves certain attention and somatic symptoms in fibromyalgia: a pilot study. Appl. Psychophysiol. Biofeedback 36, 193–200 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  101. 101

    Mathew, A., Mishra, H. & Kumaraiah, V. Alpha feedback in the treatment of tension headache. J. Pers. Clin. Stud. 3, 17–22 (1987).

    Google Scholar 

  102. 102

    Cohen, M. J., McArthur, D. L. & Rickles, W. H. Comparison of four biofeedback treatments for migraine headache: physiological and headache variables. Psychosom. Med. 42, 463–480 (1980).

    Article  CAS  Google Scholar 

  103. 103

    Andreychuk, T. & Skriver, C. Hypnosis and biofeedback in the treatment of migraine headache. Int. J. Clin. Exp. Hypn. 23, 172–183 (1975).

    Article  CAS  Google Scholar 

  104. 104

    Kayiran, S., Dursun, E., Dursun, N., Ermutlu, N. & Karamursel, S. Neurofeedback intervention in fibromyalgia syndrome; a randomized, controlled, rater blind clinical trial. Appl. Psychophysiol. Biofeedback 35, 293–302 (2010).

    Article  Google Scholar 

  105. 105

    Jensen, M. P. et al. Steps toward developing an EEG biofeedback treatment for chronic pain. Appl. Psychophysiol. Biofeedback 38, 101–108 (2013).

    Article  Google Scholar 

  106. 106

    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  Google Scholar 

  107. 107

    Jensen, M. P., Sherline, L. H., Hakimian, S. & Fregni, F. Neuromodulatory approaches for chronic pain management: research findings and clinical implications. J. Neurother. 13, 196–213 (2009).

    Article  Google Scholar 

  108. 108

    Bromm, B. & Lorenz, J. Neurophysiological evaluation of pain. Electroencephalogr. Clin. Neurophysiol. 107, 227–253 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. 109

    Chen, A. C. Human brain measures of clinical pain: a review. I. Topographic mappings. Pain 54, 115–132 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. 110

    Chen, A. C. New perspectives in EEG/MEG brain mapping and PET/fMRI neuroimaging of human pain. Int. J. Psychophysiol. 42, 147–159 (2001).

    Article  CAS  Google Scholar 

  111. 111

    Sarnthein, J., Stern, J., Aufenberg, C., Rousson, V. & Jeanmonod, D. Increased EEG power and slowed dominant frequency in patients with neurogenic pain. Brain 129, 55–64 (2006).

    Article  Google Scholar 

  112. 112

    Llinas, R., Urbano, F. J., Leznik, E., Ramirez, R. R. & van Marle, H. J. Rhythmic and dysrhythmic thalamocortical dynamics: GABA systems and the edge effect. Trends Neurosci. 28, 325–333 (2005).

    Article  CAS  Google Scholar 

  113. 113

    Jensen, M. P. et al. Brain EEG activity correlates of chronic pain in persons with spinal cord injury: clinical implications. Spinal Cord 51, 55–58 (2013).

    Article  CAS  Google Scholar 

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This work was supported by grants R01 HD070973 and R21 HD058049 from the NIH, awarded to M.P.J.

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M.P.J. and M.A.D. researched data for the article. All three authors made substantial contributions to discussions of the content, writing the article, and review and/or editing of the manuscript before submission.

Corresponding author

Correspondence to Mark P. Jensen.

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Competing interests

M.P.J. has published two books on the topic of hypnosis for chronic pain management (Hypnosis for Chronic Pain Management: Therapist Guide and Hypnosis for Chronic Pain Management: Workbook, both published by Oxford University Press), and receives royalties from the sales of these books. M.A.D. and J.M. declare no competing interests.

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Jensen, M., Day, M. & Miró, J. Neuromodulatory treatments for chronic pain: efficacy and mechanisms. Nat Rev Neurol 10, 167–178 (2014).

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