Neurophysiological Mechanisms Supporting Mindfulness Meditation–Based Pain Relief: an Updated Review


Purpose of Review

This review examines recent (2016 onwards) neuroscientific findings on the mechanisms supporting mindfulness-associated pain relief. To date, its clear that mindfulness lowers pain by engaging brain processes that are distinct from placebo and vary across meditative training level. Due to rapid developments in the field of contemplative neuroscience, an update review on the neuroimaging studies focused on mindfulness, and pain is merited.

Recent Findings

Mindfulness-based therapies produce reliably reductions in a spectrum of chronic pain conditions through psychological, physiological, and neural mechanisms supporting the modulation of evaluation and appraisal of innocuous and noxious sensory events.


Neuroimaging and randomized control studies confirm that mindfulness meditation reliably reduces experimentally induced and clinical pain by engaging multiple, unique, non-opioidergic mechanisms that are distinct from placebo and which vary across meditative training level. These promising findings underscore the potential of mindfulness-based approaches to produce long-lasting improvements in pain-related symptomology.

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

  1. 1.

    Simon LS. Relieving pain in America: a blueprint for transforming prevention, care, education, and research. J Pain Palliat Care Pharmacother. 2012;26:197–8.

    Google Scholar 

  2. 2.

    Global pain management market to reach US$60 Billion by 2015, according to a new report by Global Industry Analysts, Inc. [Internet]. Glob. Ind. Anal. Inc. [cited 2020 Apr 8]. Available from:

  3. 3.

    Tsang A, Von Korff M, Lee S, Alonso J, Karam E, Angermeyer MC, et al. Common chronic pain conditions in developed and developing countries: gender and age differences and comorbidity with depression-anxiety disorders. J Pain. 2008;9:883–91.

    PubMed  Google Scholar 

  4. 4.

    Zimmer Z, Zajacova A. Persistent, consistent, and extensive: the trend of increasing pain prevalence in older Americans. J Gerontol Ser B. 2020;75:436–47.

    Google Scholar 

  5. 5.

    Domenichiello AF, Ramsden CE. The silent epidemic of chronic pain in older adults. Prog Neuro-Psychopharmacol Biol Psychiatry. 2019;93:284–90.

    Google Scholar 

  6. 6.

    Porter J, Jick H. Addiction rare in patients treated with narcotics. N Engl J Med. 1980;302:123.

    CAS  PubMed  Google Scholar 

  7. 7.

    Volkow ND, Blanco C. The changing opioid crisis: development, challenges and opportunities. Mol Psychiatry. 2020:1–16.

  8. 8.

    Rothstein MA. The opioid crisis and the need for compassion in pain management. Am J Public Health. 2017;107:1253–4.

    PubMed  PubMed Central  Google Scholar 

  9. 9.

    Garland EL, Froeliger B, Zeidan F, Partin K, Howard MO. The downward spiral of chronic pain, prescription opioid misuse, and addiction: cognitive, affective, and neuropsychopharmacologic pathways. Neurosci Biobehav Rev. 2013;37:2597–607.

    PubMed  PubMed Central  Google Scholar 

  10. 10.

    Vowles KE, McEntee ML, Julnes PS, Frohe T, Ney JP, van der Goes DN. Rates of opioid misuse, abuse, and addiction in chronic pain: a systematic review and data synthesis. Pain. 2015;156:569–76.

    PubMed  Google Scholar 

  11. 11.

    Krebs EE, Gravely A, Nugent S, Jensen AC, DeRonne B, Goldsmith ES, et al. Effect of opioid vs nonopioid medications on pain-related function in patients with chronic back pain or hip or knee osteoarthritis pain: the SPACE randomized clinical trial. JAMA. 2018;319:872–82.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. 12.

    Hoffman EM, Watson JC, St Sauver J, Staff NP, Klein CJ. Association of long-term opioid therapy with functional status, adverse outcomes, and mortality among patients with polyneuropathy. JAMA Neurol. 2017;74:773–9.

    PubMed  PubMed Central  Google Scholar 

  13. 13.

    Ray WA, Chung CP, Murray KT, Hall K, Stein CM. Prescription of long-acting opioids and mortality in patients with chronic noncancer pain. JAMA. 2016;315:2415–23.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. 14.

    Abdel Shaheed C, Maher CG, Williams KA, Day R, McLachlan AJ. Efficacy, tolerability, and dose-dependent effects of opioid analgesics for low back pain: a systematic review and meta-analysis. JAMA Intern Med. 2016;176:958–68.

    Google Scholar 

  15. 15.

    Chou R, Deyo R, Friedly J, Skelly A, Weimer M, Fu R, et al. Systemic pharmacologic therapies for low back pain: a systematic review for an American College of Physicians Clinical Practice Guideline. Ann Intern Med. 2017;166:480–92.

    PubMed  Google Scholar 

  16. 16.

    Megale RZ, Deveza LA, Blyth FM, Naganathan V, Ferreira PH, McLachlan AJ, et al. Efficacy and safety of oral and transdermal opioid analgesics for musculoskeletal pain in older adults: a systematic review of randomized, placebo-controlled trials. J Pain. 2018;19:475.e1–475.e24.

    Google Scholar 

  17. 17.

    Duarte RV, Nevitt S, McNicol E, Taylor RS, Buchser E, North RB, et al. Systematic review and meta-analysis of placebo/sham controlled randomised trials of spinal cord stimulation for neuropathic pain. PAIN. 2020;161:24–35.

    PubMed  Google Scholar 

  18. 18.

    Deer TR, Pope JE, Hanes MC, McDowell GC. Intrathecal therapy for chronic pain: a review of morphine and ziconotide as firstline options. Pain Med Oxford Acad. 2019;20:784–98.

    Google Scholar 

  19. 19.

    Daniels J, Gray R, Hills RK, Latthe P, Buckley L, Gupta J, et al. Laparoscopic uterosacral nerve ablation for alleviating chronic pelvic pain: a randomized controlled trial. JAMA Am Med Assoc. 2009;302:955–61.

    CAS  Google Scholar 

  20. 20.

    McCormick ZL, Korn M, Reddy R, Marcolina A, Dayanim D, Mattie R, et al. Cooled radiofrequency ablation of the genicular nerves for chronic pain due to knee osteoarthritis: six-month outcomes. Pain Med Oxford Acad. 2017;18:1631–41.

    Google Scholar 

  21. 21.

    Price DD, Harkins SW, Baker C. Sensory-affective relationships among different types of clinical and experimental pain. Pain. 1987;28:297–307.

    CAS  PubMed  Google Scholar 

  22. 22.

    Zeidan F, Martucci KT, Kraft RA, Gordon NS, McHaffie JG, Coghill RC. Brain mechanisms supporting the modulation of pain by mindfulness meditation. J Neurosci. 2011;31:5540–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. 23.

    •• Zeidan F, Adler-Neal AL, Wells RE, Stagnaro E, May LM, Eisenach JC, et al. Mindfulness-meditation-based pain relief is not mediated by endogenous opioids. J Neurosci Soc Neurosci. 2016;36:3391–7 Finds that mindfulness meditation-based pain relief operates via non-opioidergic mechanisms and is thus (a) mechanistically separate from other cognitive pain inhibitory mechanisms, and (b) a good candidate for chronic pain treatment given the lack of cross-tolerance with opioid-based medications.

    CAS  Google Scholar 

  24. 24.

    Grant JA, 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. 2011;152:150–6.

    PubMed  Google Scholar 

  25. 25.

    Gard T, Hölzel BK, Sack AT, Hempel H, Lazar SW, Vaitl D, et al. Pain attenuation through mindfulness is associated with decreased cognitive control and increased sensory processing in the brain. Cereb Cortex N Y N 1991. 2012;22:2692–702.

    Google Scholar 

  26. 26.

    Brown CA, Jones AKP. Meditation experience predicts less negative appraisal of pain: electrophysiological evidence for the involvement of anticipatory neural responses. Pain. 2010;150:428–38.

    PubMed  Google Scholar 

  27. 27.

    Lutz A, McFarlin DR, Perlman DM, Salomons TV, Davidson RJ. Altered anterior insula activation during anticipation and experience of painful stimuli in expert meditators. NeuroImage. 2013;64:538–46.

    PubMed  Google Scholar 

  28. 28.

    Adler-Neal AL, Zeidan F. Mindfulness meditation for fibromyalgia: mechanistic and clinical considerations. Curr Rheumatol Rep. 2017;19:59.

    PubMed  PubMed Central  Google Scholar 

  29. 29.

    Zeidan F, Grant JA, Brown CA, McHaffie JG, Coghill RC. Mindfulness meditation-related pain relief: evidence for unique brain mechanisms in the regulation of pain. Neurosci Lett. 2012;520:165–73.

    CAS  PubMed  PubMed Central  Google Scholar 

  30. 30.

    Zeidan F, Baumgartner JN, Coghill RC. The neural mechanisms of mindfulness-based pain relief: a functional magnetic resonance imaging-based review and primer. PAIN Rep. 2019;4:e759.

    PubMed  PubMed Central  Google Scholar 

  31. 31.

    Zeidan F, Vago D. Mindfulness meditation–based pain relief: a mechanistic account. Ann N Y Acad Sci. 2016;1373:114–27.

    PubMed  PubMed Central  Google Scholar 

  32. 32.

    Wiech K, Ploner M, Tracey I. Neurocognitive aspects of pain perception. Trends Cogn Sci. 2008;12:306–13.

    PubMed  Google Scholar 

  33. 33.

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

    CAS  Google Scholar 

  34. 34.

    Derbyshire SW, Jones AK, Gyulai F, Clark S, Townsend D, Firestone LL. Pain processing during three levels of noxious stimulation produces differential patterns of central activity. Pain. 1997;73:431–45.

    CAS  PubMed  Google Scholar 

  35. 35.

    Basbaum AI, Fields HL. Endogenous pain control systems: brainstem spinal pathways and endorphin circuitry. Annu Rev Neurosci. 1984;7:309–38.

    CAS  PubMed  Google Scholar 

  36. 36.

    Coghill RC, Talbot JD, Evans AC, Meyer E, Gjedde A, Bushnell MC, et al. Distributed processing of pain and vibration by the human brain. J Neurosci. 1994;14:4095–108.

    CAS  PubMed  PubMed Central  Google Scholar 

  37. 37.

    Coghill RC, Sang CN, Maisog JM, Iadarola MJ. Pain intensity processing within the human brain: a bilateral, distributed mechanism. J Neurophysiol. 1999;82:1934–43.

    CAS  PubMed  Google Scholar 

  38. 38.

    Coghill RC, McHaffie JG, Yen Y-F. Neural correlates of interindividual differences in the subjective experience of pain. Proc Natl Acad Sci U S A. 2003;100:8538–42.

    CAS  PubMed  PubMed Central  Google Scholar 

  39. 39.

    Lobanov OV, Quevedo AS, Hadsel MS, Kraft RA, Coghill RC. Frontoparietal mechanisms supporting attention to location and intensity of painful stimuli. Pain. 2013;154:1758–68.

    PubMed  PubMed Central  Google Scholar 

  40. 40.

    Lobanov OV, Zeidan F, McHaffie JG, Kraft RA, Coghill RC. From cue to meaning: brain mechanisms supporting the construction of expectations of pain. Pain. 2014;155:129–36.

    PubMed  Google Scholar 

  41. 41.

    Oshiro Y, Quevedo AS, McHaffie JG, Kraft RA, Coghill RC. Brain mechanisms supporting spatial discrimination of pain. J Neurosci. 2007;27:3388–94.

    CAS  PubMed  PubMed Central  Google Scholar 

  42. 42.

    Oshiro Y, Quevedo AS, McHaffie JG, Kraft RA, Coghill RC. Brain mechanisms supporting discrimination of sensory features of pain: a new model. J Neurosci. 2009;29:14924–31.

    CAS  PubMed  PubMed Central  Google Scholar 

  43. 43.

    Villemure C, Bushnell MC. Cognitive modulation of pain: how do attention and emotion influence pain processing? Pain. 2002;95:195–9.

    PubMed  Google Scholar 

  44. 44.

    Koyama T, McHaffie JG, Laurienti PJ, Coghill RC. The subjective experience of pain: where expectations become reality. Proc Natl Acad Sci U S A. 2005;102:12950–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  45. 45.

    Seminowicz DA, Mikulis DJ, Davis KD. Cognitive modulation of pain-related brain responses depends on behavioral strategy. Pain. 2004;112:48–58.

    CAS  PubMed  Google Scholar 

  46. 46.

    Amanzio M, Benedetti F. Neuropharmacological dissection of placebo analgesia: expectation-activated opioid systems versus conditioning-activated specific subsystems. J Neurosci. 1999;19:484–94.

    CAS  PubMed  PubMed Central  Google Scholar 

  47. 47.

    Eippert F, Bingel U, Schoell ED, Yacubian J, Klinger R, Lorenz J, et al. Activation of the opioidergic descending pain control system underlies placebo analgesia. Neuron. 2009;63:533–43.

    CAS  Google Scholar 

  48. 48.

    Grevert P, Albert LH, Goldstein A. Partial antagonism of placebo analgesia by naloxone. Pain. 1983;16:129–43.

    CAS  PubMed  Google Scholar 

  49. 49.

    Levine JD, Gordon NC, Fields HL. The mechanism of placebo analgesia. Lancet Lond Engl. 1978;2:654–7.

    CAS  Google Scholar 

  50. 50.

    Wager TD, Scott DJ, Zubieta J-K. Placebo effects on human mu-opioid activity during pain. Proc Natl Acad Sci U S A. 2007;104:11056–61.

    CAS  PubMed  PubMed Central  Google Scholar 

  51. 51.

    Zubieta J-K, Bueller JA, Jackson LR, Scott DJ, Xu Y, Koeppe RA, et al. Placebo effects mediated by endogenous opioid activity on mu-opioid receptors. J Neurosci. 2005;25:7754–62.

    CAS  PubMed  PubMed Central  Google Scholar 

  52. 52.

    King CD, Goodin B, Kindler LL, Caudle RM, Edwards RR, Gravenstein N, et al. Reduction of conditioned pain modulation in humans by naltrexone: an exploratory study of the effects of pain catastrophizing. J Behav Med. 2013;36:315–27.

    PubMed  Google Scholar 

  53. 53.

    Harris RE, Zubieta J-K, Scott DJ, Napadow V, Gracely RH, Clauw DJ. Traditional Chinese acupuncture and placebo (sham) acupuncture are differentiated by their effects on mu-opioid receptors (MORs). NeuroImage. 2009;47:1077–85.

    CAS  PubMed  PubMed Central  Google Scholar 

  54. 54.

    Stephenson JB. Reversal of hypnosis-induced analgesia by naloxone. Lancet Lond Engl. 1978;2:991–2.

    CAS  Google Scholar 

  55. 55.

    Sprenger C, Eippert F, Finsterbusch J, Bingel U, Rose M, Büchel C. Attention modulates spinal cord responses to pain. Curr Biol CB. 2012;22:1019–22.

    CAS  PubMed  Google Scholar 

  56. 56.

    Beitz AJ. The organization of afferent projections to the midbrain periaqueductal gray of the rat. Neuroscience. 1982;7:133–59.

    CAS  PubMed  Google Scholar 

  57. 57.

    Mantyh PW. Connections of midbrain periaqueductal gray in the monkey. I. Ascending efferent projections. J Neurophysiol. 1983;49:567–81.

    CAS  PubMed  Google Scholar 

  58. 58.

    Mantyh PW. Connections of midbrain periaqueductal gray in the monkey. II. Descending efferent projections. J Neurophysiol. 1983;49:582–94.

    CAS  PubMed  Google Scholar 

  59. 59.

    Liebeskind JC, Guilbaud G, Besson JM, Oliveras JL. Analgesia from electrical stimulation of the periaqueductal gray matter in the cat: behavioral observations and inhibitory effects on spinal cord interneurons. Brain Res. 1973;50:441–6.

    CAS  PubMed  Google Scholar 

  60. 60.

    Kabat-Zinn J, Hanh TN. Full catastrophe living: using the wisdom of your body and mind to face stress, pain, and illness: Random House Publishing Group; 2009.

  61. 61.

    Lutz A, Slagter HA, Dunne JD, Davidson RJ. Attention regulation and monitoring in meditation. Trends Cogn Sci. 2008;12:163–9.

    PubMed  PubMed Central  Google Scholar 

  62. 62.

    Garrison KA, Zeffiro TA, Scheinost D, Constable RT, Brewer JA. Meditation leads to reduced default mode network activity beyond an active task. Cogn Affect Behav Neurosci. 2015;15:712–20.

    PubMed  PubMed Central  Google Scholar 

  63. 63.

    Josipovic Z. Neural correlates of nondual awareness in meditation. Ann N Y Acad Sci. 2014;1307:9–18.

    PubMed  Google Scholar 

  64. 64.

    Kabat-Zinn J. Some reflections on the origins of MBSR, skillful means, and the trouble with maps. Contemp Buddhism Routledge. 2011;12:281–306.

    Google Scholar 

  65. 65.

    Kuyken W, Byford S, Taylor RS, Watkins E, Holden E, White K, et al. Mindfulness-based cognitive therapy to prevent relapse in recurrent depression. J Consult Clin Psychol. 2008;76:966–78.

    PubMed  Google Scholar 

  66. 66.

    Segal ZV, Williams JMG, Teasdale JD, Kabat-Zinn J. Mindfulness-based cognitive therapy for depression. New York: The Guilford Press; 2012.

    Google Scholar 

  67. 67.

    Segal ZV, Bieling P, Young T, MacQueen G, Cooke R, Martin L, et al. Antidepressant monotherapy vs sequential pharmacotherapy and mindfulness-based cognitive therapy, or placebo, for relapse prophylaxis in recurrent depression. Arch Gen Psychiatry. 2010;67:1256–64.

    PubMed  PubMed Central  Google Scholar 

  68. 68.

    Segal ZV, Dimidjian S, Beck A, Boggs JM, Vanderkruik R, Metcalf CA, et al. 2020 Outcomes of online mindfulness-based cognitive therapy for patients with residual depressive symptoms: a randomized clinical trial. JAMA Psychiatry [Internet]. [cited 2020 Apr 20]; Available from:

  69. 69.

    Garland EL, Howard MO. Mindfulness-oriented recovery enhancement reduces pain attentional bias in chronic pain patients. Psychother Psychosom. 2013;82:311–8.

    PubMed  Google Scholar 

  70. 70.

    Bowen S, Witkiewitz K, Clifasefi SL, Grow J, Chawla N, Hsu SH, et al. Relative efficacy of mindfulness-based relapse prevention, standard relapse prevention, and treatment as usual for substance use disorders: a randomized clinical trial. JAMA Psych Am Med Assoc. 2014;71:547–56.

    Google Scholar 

  71. 71.

    Morone NE, Greco CM, Moore CG, Rollman BL, Lane B, Morrow LA, et al. A mind-body program for older adults with chronic low Back pain: a randomized clinical trial. JAMA Intern Med. 2016;176:329–37.

    PubMed  PubMed Central  Google Scholar 

  72. 72.

    Cho S, Heiby EM, McCracken LM, Lee S-M, Moon D-E. Pain-related anxiety as a mediator of the effects of mindfulness on physical and psychosocial functioning in chronic pain patients in Korea. J Pain Off J Am Pain Soc. 2010;11:789–97.

    Google Scholar 

  73. 73.

    Fox SD, Flynn E, Allen RH. Mindfulness meditation for women with chronic pelvic pain: a pilot study. J Reprod Med. 2011;56:158–62.

    PubMed  Google Scholar 

  74. 74.

    Ussher M, Spatz A, Copland C, Nicolaou A, Cargill A, Amini-Tabrizi N, et al. Immediate effects of a brief mindfulness-based body scan on patients with chronic pain. J Behav Med. 2014;37:127–34.

    PubMed  Google Scholar 

  75. 75.

    Garland EL, Manusov EG, Froeliger B, Kelly A, Williams JM, Howard MO. Mindfulness-oriented recovery enhancement for chronic pain and prescription opioid misuse: results from an early-stage randomized controlled trial. J Consult Clin Psychol. 2014;82:448–59.

    PubMed  PubMed Central  Google Scholar 

  76. 76.

    de Boer MJ, Steinhagen HE, Versteegen GJ, Struys MMRF, Sanderman R. Mindfulness, acceptance and catastrophizing in chronic pain. PLoS One. 2014;9:e87445.

    PubMed  PubMed Central  Google Scholar 

  77. 77.

    Morone NE, Rollman BL, Moore CG, Li Q, Weiner DK. A mind-body program for older adults with chronic low back pain: results of a pilot study. Pain Med Malden Mass. 2009;10:1395–407.

    Google Scholar 

  78. 78.

    Morone NE, Lynch CS, Greco CM, Tindle HA, Weiner DK. “I Felt Like a New Person.” The Effects of Mindfulness Meditation on Older Adults With Chronic Pain: Qualitative Narrative Analysis of Diary Entries. J Pain Off J Am Pain Soc. 2008;9:841–8.

    Google Scholar 

  79. 79.

    McCracken LM, Keogh E. Acceptance, mindfulness, and values-based action may counteract fear and avoidance of emotions in chronic pain: an analysis of anxiety sensitivity. J Pain Off J Am Pain Soc. 2009;10:408–15.

    Google Scholar 

  80. 80.

    McCracken LM, Velleman SC. Psychological flexibility in adults with chronic pain: a study of acceptance, mindfulness, and values-based action in primary care. Pain. 2010;148:141–7.

    PubMed  Google Scholar 

  81. 81.

    McCracken LM, Gauntlett-Gilbert J, Vowles KE. The role of mindfulness in a contextual cognitive-behavioral analysis of chronic pain-related suffering and disability. Pain. 2007;131:63–9.

    PubMed  Google Scholar 

  82. 82.

    Rosenzweig S, Greeson JM, Reibel DK, Green JS, Jasser SA, Beasley D. Mindfulness-based stress reduction for chronic pain conditions: variation in treatment outcomes and role of home meditation practice. J Psychosom Res. 2010;68:29–36.

    PubMed  Google Scholar 

  83. 83.

    Hilton L, Hempel S, Ewing BA, Apaydin E, Xenakis L, Newberry S, et al. Mindfulness meditation for chronic pain: systematic review and meta-analysis. Ann Behav Med Oxford Acad. 2017;51:199–213.

    Google Scholar 

  84. 84.

    DiRenzo D, Crespo-Bosque M, Gould N, Finan P, Nanavati J, Bingham CO. Systematic review and meta-analysis: mindfulness-based interventions for rheumatoid arthritis. Curr Rheumatol Rep. 2018;20:75.

    PubMed  PubMed Central  Google Scholar 

  85. 85.

    Johannsen M, O’Connor M, O’Toole MS, Jensen AB, Zachariae R. Mindfulness-based cognitive therapy and persistent pain in women treated for primary breast cancer [Internet]. Wolters Kluwer; 2018 [cited 2020 Apr 3]. Available from:

  86. 86.

    Kabat-Zinn J. An outpatient program in behavioral medicine for chronic pain patients based on the practice of mindfulness meditation: theoretical considerations and preliminary results. Gen Hosp Psychiatry. 1982;4:33–47.

    CAS  PubMed  Google Scholar 

  87. 87.

    Cherkin DC, Sherman KJ, Balderson BH, Cook AJ, Anderson ML, Hawkes RJ, et al. Effect of mindfulness-based stress reduction vs cognitive behavioral therapy or usual care on back pain and functional limitations in adults with chronic low back pain: a randomized clinical trial. JAMA. 2016;315:1240–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  88. 88.

    Kabat-Zinn J, Lipworth L, Burney R. The clinical use of mindfulness meditation for the self-regulation of chronic pain. J Behav Med. 1985;8:163–90.

    CAS  PubMed  Google Scholar 

  89. 89.

    Ruskin DA, Gagnon MM, Kohut SA, Stinson JN, Walker KS. A mindfulness program adapted for adolescents with chronic pain [Internet]. Wolters Kluwer; 2017 [cited 2020 Apr 3]. Available from:

  90. 90.

    Taren AA, Gianaros PJ, Greco CM, Lindsay EK, Fairgrieve A, Brown KW, et al. Mindfulness meditation training alters stress-related amygdala resting state functional connectivity: a randomized controlled trial. Soc Cogn Affect Neurosci. 2015;10:1758–68.

    PubMed  PubMed Central  Google Scholar 

  91. 91.

    Creswell JD, Taren AA, Lindsay EK, Greco CM, Gianaros PJ, Fairgrieve A, et al. Alterations in resting-state functional connectivity link mindfulness meditation with reduced interleukin-6: a randomized controlled trial. Biol Psychiatry. 2016;80:53–61.

    CAS  PubMed  Google Scholar 

  92. 92.

    de Jong M, Peeters F, Gard T, Ashih H, Doorley J, Walker R, et al. A randomized controlled pilot study on mindfulness-based cognitive therapy for unipolar depression in patients with chronic pain. J Clin Psychiatry [Internet]. 2018 [cited 2020 Apr 3];79. Available from:

  93. 93.

    Eisendrath S, Chartier M, McLane M. Adapting mindfulness-based cognitive therapy for treatment-resistant depression: a clinical case study. Cogn Behav Pract. 2011;18:362–70.

    PubMed  PubMed Central  Google Scholar 

  94. 94.

    Eisendrath SJ, Gillung EP, Delucchi KL, Chartier M, Mathalon DH, Sullivan JC, et al. Mindfulness-based cognitive therapy (MBCT) versus the health-enhancement program (HEP) for adults with treatment-resistant depression: a randomized control trial study protocol. BMC Complement Altern Med. 2014;14:95.

    PubMed  PubMed Central  Google Scholar 

  95. 95.

    Williams JMG, Crane C, Barnhofer T, Brennan K, Duggan DS, Fennell MJV, et al. Mindfulness-based cognitive therapy for preventing relapse in recurrent depression: a randomized dismantling trial. J Consult Clin Psychol. 2014;82:275–86.

    PubMed  Google Scholar 

  96. 96.

    Turner JA, Anderson ML, Balderson BH, Cook AJ, Sherman KJ, Cherkin DC. Mindfulness-based stress reduction and cognitive-behavioral therapy for chronic low back pain: similar effects on mindfulness, catastrophizing, self-efficacy, and acceptance in a randomized controlled trial. Pain. 2016;157:2434–44.

    PubMed  PubMed Central  Google Scholar 

  97. 97.

    Tang Y-Y, Hölzel BK, Posner MI. The neuroscience of mindfulness meditation. Nat Rev Neurosci Nature Publish Group. 2015;16:213–25.

    CAS  Google Scholar 

  98. 98.

    Zeidan F, Emerson NM, Farris SR, Ray JN, Jung Y, McHaffie JG, et al. Mindfulness meditation-based pain relief employs different neural mechanisms than placebo and sham mindfulness meditation-induced analgesia. J Neurosci. 2015;35:15307–25.

    CAS  PubMed  PubMed Central  Google Scholar 

  99. 99.

    Perlman DM, Salomons TV, Davidson RJ, Lutz A. Differential effects on pain intensity and unpleasantness of two meditation practices. Emot Wash DC. 2010;10:65–71.

    Google Scholar 

  100. 100.

    May LM, Kosek P, Zeidan F, Berkman ET. Enhancement of meditation analgesia by opioid antagonist in experienced meditators. Psychosom Med. 2018;80:807–13.

    CAS  PubMed  PubMed Central  Google Scholar 

  101. 101.

    Wells RE, Collier J, Posey G, Morgan F, Auman T, Strittameter B, et al. Attention to breath sensations does not engage endogenous opioids to reduce pain. PAIN [Internet]. 2020 [cited 2020 Apr 4];Articles in Press. Available from:

  102. 102.

    Smith KE, Norman GJ. Brief relaxation training is not sufficient to alter tolerance to experimental pain in novices. PLoS ONE [Internet]. 2017 [cited 2020 Apr 9];12. Available from:

  103. 103.

    Adler-Neal AL, Waugh CE, Garland EL, Shaltout HA, Diz DI, Zeidan F. The role of heart rate variability in mindfulness-based pain relief. J Pain [Internet]. 2019 [cited 2020 Apr 4]; Available from:

  104. 104.

    Kober H, Buhle J, Weber J, Ochsner KN, Wager TD. Let it be: mindful acceptance down-regulates pain and negative emotion. Soc Cogn Affect Neurosci Oxford Acad. 2019;14:1147–58.

    Google Scholar 

  105. 105.

    Wager TD, Atlas LY, Lindquist MA, Roy M, Woo C-W, Kross E. An fMRI-based neurologic signature of physical pain. N Engl J Med. 2013;368:1388–97.

    CAS  PubMed  PubMed Central  Google Scholar 

  106. 106.

    Laneri D, Krach S, Paulus FM, Kanske P, Schuster V, Sommer J, et al. Mindfulness meditation regulates anterior insula activity during empathy for social pain. Hum Brain Mapp. 2017;38:4034–46.

    PubMed  PubMed Central  Google Scholar 

  107. 107.

    Paulus FM, Müller-Pinzler L, Jansen A, Gazzola V, Krach S. Mentalizing and the role of the posterior superior temporal sulcus in sharing others’ embarrassment. Cereb Cortex N Y N 1991. 2015;25:2065–75.

    Google Scholar 

  108. 108.

    Fan Y, Duncan NW, de Greck M, Northoff G. Is there a core neural network in empathy? An fMRI based quantitative meta-analysis. Neurosci Biobehav Rev. 2011;35:903–11.

    PubMed  Google Scholar 

  109. 109.

    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. 2011;54:2492–502.

    PubMed  Google Scholar 

  110. 110.

    Haase L, Thom NJ, Shukla A, Davenport PW, Simmons AN, Stanley EA, et al. Mindfulness-based training attenuates insula response to an aversive interoceptive challenge. Soc Cogn Affect Neurosci. 2016;11:182–90.

    PubMed  Google Scholar 

  111. 111.

    Paul NA, Stanton SJ, Greeson JM, Smoski MJ, Wang L. Psychological and neural mechanisms of trait mindfulness in reducing depression vulnerability. Soc Cogn Affect Neurosci Oxford Acad. 2013;8:56–64.

    Google Scholar 

  112. 112.

    Ashar YK, Andrews-Hanna JR, Dimidjian S, Wager TD. Empathic care and distress: predictive brain markers and dissociable brain systems. Neuron. 2017;94:1263–1273.e4.

    CAS  PubMed  PubMed Central  Google Scholar 

  113. 113.

    Edwards RR, Dworkin RH, Sullivan MD, Turk DC, Wasan AD. The role of psychosocial processes in the development and maintenance of chronic pain. J Pain. 2016;17:T70–92.

    PubMed  PubMed Central  Google Scholar 

  114. 114.

    •• Seminowicz DA, Burrowes SAB, Kearson A, Zhang J, Krimmel SR, Samawi L, et al. Enhanced mindfulness-based stress reduction in episodic migraine: a randomized clinical trial with magnetic resonance imaging outcomes. PAIN. 2020;Articles in Press. Available from: Finds that Enhanced Mindfulness-Based Stress Relief reduces episodic migraine significantly more than a stress management for headache (SMH) program at a therapeutic response rate comparable to that of first-line pharmacologic treatment. fMRI data suggests increased cognitive efficiency from mindfulness-based training.

  115. 115.

    Elman I, Borsook D. Common brain mechanisms of chronic pain and addiction. Neuron. 2016;89:11–36.

    CAS  PubMed  Google Scholar 

  116. 116.

    Garland EL, Farb NA, Goldin PR, Fredrickson BL. The mindfulness-to-meaning theory: extensions, applications, and challenges at the attention–appraisal–emotion Interface. Psychol Inq Routledge. 2015;26:377–87.

    Google Scholar 

  117. 117.

    • Garland EL, Hanley AW, Riquino MR, Reese SE, Baker AK, Salas K, et al. Mindfulness-oriented recovery enhancement reduces opioid misuse risk via analgesic and positive psychological mechanisms: a randomized controlled trial. J Consult Clin Psychol Am Psycholog Assoc. 2019;87:927–40 Finds that Mindfulness-Oriented Recovery Enhancement (MORE) is effective as a prophylactic to prevent long-term opioid-treated chronic pain patients from developing opioid misuse disorder while reducing pain severity and significantly improving an array of positive psychological functions.

    Google Scholar 

  118. 118.

    Garland EL, Atchley RM, Hanley AW, Zubieta J-K, Froeliger B. Mindfulness-oriented recovery enhancement remediates hedonic dysregulation in opioid users: neural and affective evidence of target engagement. Sci Adv. 2019;5:eaax1569.

    CAS  PubMed  PubMed Central  Google Scholar 

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This work was supported by the NIH’s National Center for Complementary and Integrative Health (NCCIH) (K99/R00-AT008238; R21-AT007247; R01-AT009693; R21-AT010352, FZ).

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Correspondence to Fadel Zeidan.

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This article is part of the Topical Collection on Psychological and Behavioral Aspects of Headache with Pain

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Jinich-Diamant, A., Garland, E., Baumgartner, J. et al. Neurophysiological Mechanisms Supporting Mindfulness Meditation–Based Pain Relief: an Updated Review. Curr Pain Headache Rep 24, 56 (2020).

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  • Pain
  • Mindfulness
  • Meditation
  • Analgesia