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Elin Johansson
Elin Johansson
Pain in Motion Research Group (PAIN), Department of Physiotherapy, Human Physiology and Anatomy, Faculty of Physical Education & Physiotherapy, Vrije Universiteit Brussel, Belgium
-
Iris Coppieters
Iris Coppieters
Pain in Motion Research Group (PAIN), Department of Physiotherapy, Human Physiology and Anatomy, Faculty of Physical Education & Physiotherapy, Vrije Universiteit Brussel, Belgium
-
Jo Nijs
Jo Nijs
Pain in Motion Research Group (PAIN), Department of Physiotherapy, Human Physiology and Anatomy, Faculty of Physical Education & Physiotherapy, Vrije Universiteit Brussel, Belgium
Published Date
- Jul 4, 2023
The default mode of chronic pain: What does it mean and how should we frame it to our patients?
Abstract
The brain can be organised into defined networks based on the coherent activity fluctuations between certain regions at rest when no external task or stimuli are applied. In patients with chronic pain, alterations in the way these networks act and interact become apparent, especially within the default mode network (DMN) and in the way it functionally interacts with the salience network (SN). However, the implications of these cortical alterations remain speculative, and a clear framework for how we might explain the meaning of them to the patient with chronic pain is lacking. Therefore, here we provide an up-to-date theoretical model for the implications of the DMN alterations observed in the state of chronic pain, and to integrate the key points of this model into an explanatory framework to use in the clinical meeting with chronic pain patients (e.g., during pain neuroscience education).
Keywords:
Default mode network, Salience network, Chronic pain, Pain neuroscience education, Attention, Threat appraisal
References
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[31] Fox MD, Zhang D, Snyder AZ, Raichle ME. The global signal and observed anticorrelated resting state brain networks. J Neurophysiol 2009; 101(6): 3270–3283.
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[35] Loggia ML, Kim J, Gollub RL, Vangel MG, Kirsch I, Kong J, et al. Default mode network connectivity encodes clinical pain: An arterial spin labeling study. Pain 2013; 154(1): 24– 33.
[36] Baliki MN, Baria AT, Vania Apkarian A. The cortical rhythms of chronic back pain. J Neurosci 2011; 31(39): 13981–13990.
[37] Napadow V, LaCount L, Park K, As-Sanie S, Clauw DJ, Harris RE. Intrinsic brain connectivity in fibromyalgia is associated with chronic pain intensity. Arthritis Rheum 2010; 62(8): 2545–2555.
[38] Van Ettinger-Veenstra H, Lundberg P, Alföldi P, Södermark M, Graven-Nielsen T, Sjörs A, et al. Chronic widespread pain patients show disrupted cortical connectivity in default mode and salience networks, modulated by pain sensitivity. J Pain Res 2019; 12: 1743–1755.
[39] Bolwerk A, Seifert F, Maihöfner C. Altered restingstate functional connectivity in complex regional pain syndrome. J Pain 2013; 14(10): 1107–1115.e8.
[40] Kucyi A, Moayedi M, Weissman-Fogel I, Goldberg MB, Freeman BV, Tenenbaum HC, et al. Enhanced medial prefrontal-default mode network functional connectivity in chronic pain and its association with pain rumination. J Neurosci 2014; 34(11): 3969–3975.
[41] Kim J, Mawla I, Kong J, Lee J, Gerber J, Ortiz A, et al. Somatotopically specific primary somatosensory connectivity to salience and default mode networks encodes clinical pain. Pain 2019; 160(7): 1594–1605.
[42] Menon V, Uddin LQ. Saliency, switching, attention and control: A network model of insula function. Brain Struct Funct 2010; 214(5–6): 655–667.
[43] Sridharan D, Levitin DJ, Menon V. A critical role for the right fronto-insular cortex in switching between centralexecutive and default-mode networks. Proc Natl Acad Sci U S A 2008; 105(34): 12569–12574.
[44] Goulden N, Khusnulina A, Davis NJ, Bracewell RM, Bokde AL, McNulty JP, et al. The salience network is responsible for switching between the default mode network and the central executive network: Replication from DCM. Neuroimage 2014; 99: 180–190.
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[46] Čeko M, Gracely JL, Fitzcharles MA, Seminowicz DA, Schweinhardt P, Bushnell MC. Is a responsive default mode network required for successful working memory task performance? J Neurosci 2015; 35(33): 11595–11605.
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[48] Weissman-Fogel I, Moayedi M, Tenenbaum HC, Goldberg MB, Freeman BV, Davis KD. Abnormal cortical activity in patients with temporomandibular disorder evoked by cognitive and emotional tasks. Pain 2011; 152(2): 384–396.
[49] Marstaller L, Burianová H, Reutens DC. Adaptive contextualization: A new role for the default mode network in affective learning. Hum Brain Mapp 2017; 38(2): 1082–1091.
[50] Wiech K, Lin CS, Brodersen KH, Bingel U, Ploner M, Tracey I. Anterior insula integrates information about salience into perceptual decisions about pain. J Neurosci 2010; 30(48): 16324–16331.
[51] Ploner M, Lee MC, Wiech K, Bingel U, Tracey I. Prestimulus functional connectivity determines pain perception in humans. Proc Natl Acad Sci U S A 2010; 107(1): 355–360.
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[53] Fullana MA, Harrison BJ, Soriano-Mas C, Vervliet B, Cardoner N, Àvila-Parcet A, et al. Neural signatures of human fear conditioning: An updated and extended metaanalysis of f MRI studies. Mol Psychiatry 2016; 21(4): 500– 508.
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[56] Wager TD, Atlas LY. The neuroscience of placebo effects: Connecting context, learning and health. Nat Rev Neurosci 2015; 16(7): 403–418.
[57] Ashar YK, Chang LJ, Wager TD. Brain mechanisms of the placebo effect: An affective appraisal account. Annu Rev Clin Psychol 2017; 13: 73–89.
[58] Benedetti F. Placebo effects: From the neurobiological paradigm to translational implications. Neuron 2014; 84(3): 623–637.
[59] Wager TD, Atlas LY, Leotti LA, Rilling JK. Predicting individual differences in placebo analgesia: Contributions of brain activity during anticipation and pain experience. J Neurosci 2011; 31(2): 439–452.
[60] Roy M, Shohamy D, Daw N, Jepma M, Wimmer GE, Wager TD. Representation of aversive prediction errors in the human periaqueductal gray. Nat Neurosci 2014; 17(11): 1607–1612.
[61] Roy M, Shohamy D, Wager TD. Ventromedial prefrontalsubcortical systems and the generation of affective meaning. Trends Cogn Sci 2012; 16(3): 147–156.
[62] White LK, Helfinstein SM, Reeb-Sutherland BC, Degnan KA, Fox NA. Role of attention in the regulation of fear and anxiety. Dev Neurosci 2009; 31(4): 309–317.
[63] Moseley GL. Whole of community pain education for back pain. Why does first-line care get almost no attention and what exactly are we waiting for? Br J Sports Med 2019; 53(10): 588–589.
[64] Bernstein IA, Malik Q, Carville S, Ward S. Low back pain and sciatica: Summary of NICE guidance. BMJ 2017; 356: 10–13.
[65] Harden RN, Oaklander AL, Burton AW, Perez RSGM, Richardson K, Swan M, et al. Complex regional pain syndrome: Practical diagnostic and treatment guidelines, 4th edition. Pain Med 2013; 14(2): 180–229.
[66] Lin I, Wiles L, Waller R, Goucke R, Nagree Y, Gibberd M, et al. What does best practice care for musculoskeletal pain look like? Eleven consistent recommendations from highquality clinical practice guidelines: Systematic review. Br J Sports Med 2020; 54(2): 79–86.
[67] Leake HB, Moseley GL, Stanton TR, O’Hagan ET, Heathcote LC. What do patients value learning about pain? A mixed-methods survey on the relevance of target concepts after pain science education. Pain 2021; 162(10): 2558–2568.
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[2] Apkarian A, Bushnell M, Treede R, Zubieta J. Human brain mechanisms of pain perception and regulation in health and disease. Eur J Pain 2005; 9(4): 463–484.
[3] Kuner R, Flor H. Structural plasticity and reorganisation in chronic pain. Nat Rev Neurosci 2016; 18(1): 20–30.
[4] Coppieters I, Meeus M, Kregel J, Caeyenberghs K, De Pauw R, Goubert D, et al. Relations between brain alterations and clinical pain measures in chronic musculoskeletal pain: A systematic review. J Pain 2016; 17(9): 949–962.
[5] Malfliet A, Coppieters I, Van Wilgen P, Kregel J, De Pauw R, Dolphens M, et al. Brain changes associated with cognitive and emotional factors in chronic pain: A systematic review. Eur J Pain 2017; 21(5): 769–786.
[6] Fox MD, Raichle ME. Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging. Nat Rev Neurosci 2007; 8(9): 700–711.
[7] Raichle ME, MacLeod AM, Snyder AZ, Powers WJ, Gusnard DA, Shulman GL. A default mode of brain function. Proc Natl Acad Sci U S A 2001; 98(2): 676–682.
[8] Seeley WW, Menon V, Schatzberg AF, Keller J, Glover GH, Kenna H, et al. Dissociable intrinsic connectivity networks for salience processing and executive control. J Neurosci 2007; 27(9): 2349–2356.
[9] Corbetta M, Shulman GL. Control of goal-directed and stimulus-driven attention in the brain. Nat Rev Neurosci 2002; 3(3): 201–215.
[10] Baliki MN, Mansour AR, Baria AT, Apkarian AV. Functional reorganization of the default mode network across chronic pain conditions. PLoS One 2014; 9(9).
[11] Tu Y, Jung M, Gollub RL, Napadow V, Gerber J, Ortiz A, et al. Abnormal medial prefrontal cortex functional connectivity and its association with clinical symptoms in chronic low back pain. Pain 2019; 160(6): 1308–1318.
[12] Andrews-Hanna JR, Smallwood J, Spreng RN. The default network and self-generated thought: Component processes, dynamic control, and clinical relevance. Ann N Y Acad Sci 2014; 1316(1): 29–52.
[13] Kucyi A, Davis KD. The dynamic pain connectome. Trends Neurosci 2015; 38(2): 86–95.
[14] De Ridder D, Vanneste S, Smith M, Adhia D. Pain and the Triple Network Model. Front Neurol 2022; 13(March): 1–13.
[15] Farmer MA, Baliki MN, Apkarian AV. A dynamic network perspective of chronic pain. Neurosci Lett 2012; 520(2): 197–203.
[16] Raichle ME. The brain’s default mode network. Annu Rev Neurosci 2015; 38: 433–447.
[17] Buckner RL, Andrews-Hanna JR, Schacter DL. The brain’s default network: Anatomy, function, and relevance to disease. Ann N Y Acad Sci 2008; 1124: 1–38.
[18] Andrews-Hanna JR, Reidler JS, Huang C, Buckner RL. Evidence for the default network’s role in spontaneous cognition. J Neurophysiol 2010; 104(1): 322–335.
[19] Andrews-hanna JR, Reidler JS, Sepulcre J, Poulin R, Buckner RL. Functional-anatomic fractionation of the brain’s default network. Neuron 2010; 65(4): 550–562.
[20] Buckner RL, DiNicola LM. The brain’s default network: Updated anatomy, physiology and evolving insights. Nat Rev Neurosci 2019; 20(10): 593–608.
[21] Seminowicz DA, Davis KD. Pain enhances functional connectivity of a brain network evoked by performance of a cognitive task. J Neurophysiol 2007; 97(5): 3651–3659.
[22] Kong J, Loggia ML, Zyloney C, Tu P, LaViolette P, Gollub RL. Exploring the brain in pain: Activations, deactivations and their relation. Pain 2010; 148(2): 257–267.
[23] Loggia ML, Edwards RR, Kim J, Vangel MG, Wasan AD, Gollub RL, et al. Disentangling linear and nonlinear brain responses to evoked deep tissue pain. Pain 2012; 153(10): 2140–2151.
[24] Kucyi A, Salomons TV, Davis KD. Mind wandering away from pain dynamically engages antinociceptive and default mode brain networks. Proc Natl Acad Sci U S A 2013; 110(46): 18692–18697.
[25] Alhajri N, Boudreau SA, Graven-Nielsen T. Decreased default mode network connectivity following 24 hours of capsaicin-induced pain persists during immediate pain relief and facilitation. J Pain 2022. https://doi.org/10.1016/j.jpain.2022.12.004
[26] Damascelli M, Woodward TS, Sanford N, Zahid HB, Lim R, Scott A, et al. Multiple functional brain networks related to pain perception revealed by f MRI. Neuroinformatics 2022; 20(1): 155–172.
[27] Alshelh Z, Marciszewski KK, Akhter R, Di Pietro F, Mills EP, Vickers ER, et al. Disruption of default mode network dynamics in acute and chronic pain states. NeuroImage Clin 2018; 17: 222–231.
[28] Seeley WW. The salience network: A neural system for perceiving and responding to homeostatic demands. J Neurosci 2019; 39(50): 9878–9882.
[29] Bartra O, McGuire JT, Kable JW. The valuation system: A coordinate-based meta-analysis of BOLD f MRI experiments examining neural correlates of subjective value. Neuroimage 2013; 76: 412–427.
[30] Fox MD, Corbetta M, Snyder AZ, Vincent JL, Raichle ME. Spontaneous neuronal activity distinguishes human dorsal and ventral attention systems. Proc Natl Acad Sci U S A 2006; 103(26): 10046–10051.
[31] Fox MD, Zhang D, Snyder AZ, Raichle ME. The global signal and observed anticorrelated resting state brain networks. J Neurophysiol 2009; 101(6): 3270–3283.
[32] Eccleston C, Crombez G. Pain demands attention: A cognitive-affective model of the interruptive function of pain. Psychol Bull 1999; 125(3): 356–366.
[33] Čeko M, Frangos E, Gracely J, Richards E, Wang B, Schweinhardt P, et al. Default mode network changes in fibromyalgia patients are largely dependent on current clinical pain. Neuroimage 2020; 216: 116877.
[34] Hemington KS, Wu Q, Kucyi A, Inman RD, Davis KD. Abnormal cross-network functional connectivity in chronic pain and its association with clinical symptoms. Brain Struct Funct 2016; 221(8): 4203–4219.
[35] Loggia ML, Kim J, Gollub RL, Vangel MG, Kirsch I, Kong J, et al. Default mode network connectivity encodes clinical pain: An arterial spin labeling study. Pain 2013; 154(1): 24– 33.
[36] Baliki MN, Baria AT, Vania Apkarian A. The cortical rhythms of chronic back pain. J Neurosci 2011; 31(39): 13981–13990.
[37] Napadow V, LaCount L, Park K, As-Sanie S, Clauw DJ, Harris RE. Intrinsic brain connectivity in fibromyalgia is associated with chronic pain intensity. Arthritis Rheum 2010; 62(8): 2545–2555.
[38] Van Ettinger-Veenstra H, Lundberg P, Alföldi P, Södermark M, Graven-Nielsen T, Sjörs A, et al. Chronic widespread pain patients show disrupted cortical connectivity in default mode and salience networks, modulated by pain sensitivity. J Pain Res 2019; 12: 1743–1755.
[39] Bolwerk A, Seifert F, Maihöfner C. Altered restingstate functional connectivity in complex regional pain syndrome. J Pain 2013; 14(10): 1107–1115.e8.
[40] Kucyi A, Moayedi M, Weissman-Fogel I, Goldberg MB, Freeman BV, Tenenbaum HC, et al. Enhanced medial prefrontal-default mode network functional connectivity in chronic pain and its association with pain rumination. J Neurosci 2014; 34(11): 3969–3975.
[41] Kim J, Mawla I, Kong J, Lee J, Gerber J, Ortiz A, et al. Somatotopically specific primary somatosensory connectivity to salience and default mode networks encodes clinical pain. Pain 2019; 160(7): 1594–1605.
[42] Menon V, Uddin LQ. Saliency, switching, attention and control: A network model of insula function. Brain Struct Funct 2010; 214(5–6): 655–667.
[43] Sridharan D, Levitin DJ, Menon V. A critical role for the right fronto-insular cortex in switching between centralexecutive and default-mode networks. Proc Natl Acad Sci U S A 2008; 105(34): 12569–12574.
[44] Goulden N, Khusnulina A, Davis NJ, Bracewell RM, Bokde AL, McNulty JP, et al. The salience network is responsible for switching between the default mode network and the central executive network: Replication from DCM. Neuroimage 2014; 99: 180–190.
[45] Sullivan M, Bishop S, Pivik J. The pain catastrophizing scale: Development and validation. Psychol Assess 1995; 7(4): 524–532.
[46] Čeko M, Gracely JL, Fitzcharles MA, Seminowicz DA, Schweinhardt P, Bushnell MC. Is a responsive default mode network required for successful working memory task performance? J Neurosci 2015; 35(33): 11595–11605.
[47] Baliki MN, Geha PY, Apkarian AV, Chialvo DR. Beyond feeling: Chronic pain hurts the brain, disrupting the default-mode network dynamics. J Neurosci 2008; 28(6): 1398–1403.
[48] Weissman-Fogel I, Moayedi M, Tenenbaum HC, Goldberg MB, Freeman BV, Davis KD. Abnormal cortical activity in patients with temporomandibular disorder evoked by cognitive and emotional tasks. Pain 2011; 152(2): 384–396.
[49] Marstaller L, Burianová H, Reutens DC. Adaptive contextualization: A new role for the default mode network in affective learning. Hum Brain Mapp 2017; 38(2): 1082–1091.
[50] Wiech K, Lin CS, Brodersen KH, Bingel U, Ploner M, Tracey I. Anterior insula integrates information about salience into perceptual decisions about pain. J Neurosci 2010; 30(48): 16324–16331.
[51] Ploner M, Lee MC, Wiech K, Bingel U, Tracey I. Prestimulus functional connectivity determines pain perception in humans. Proc Natl Acad Sci U S A 2010; 107(1): 355–360.
[52] Mechias ML, Etkin A, Kalisch R. A meta-analysis of instructed fear studies: Implications for conscious appraisal of threat. Neuroimage 2010; 49(2): 1760–1768.
[53] Fullana MA, Harrison BJ, Soriano-Mas C, Vervliet B, Cardoner N, Àvila-Parcet A, et al. Neural signatures of human fear conditioning: An updated and extended metaanalysis of f MRI studies. Mol Psychiatry 2016; 21(4): 500– 508.
[54] Etkin A, Egner T, Kalisch R. Emotional processing in anterior cingulate and medial prefrontal cortex. Trends Cogn Sci 2011; 15(2): 85–93.
[55] Raja SN, Carr DB, Cohen M, Finnerup NB, Flor H, Gibson S, et al. The revised International Association for the Study of Pain definition of pain: Concepts, challenges, and compromises. Pain 2020; 161(9): 1976–1982.
[56] Wager TD, Atlas LY. The neuroscience of placebo effects: Connecting context, learning and health. Nat Rev Neurosci 2015; 16(7): 403–418.
[57] Ashar YK, Chang LJ, Wager TD. Brain mechanisms of the placebo effect: An affective appraisal account. Annu Rev Clin Psychol 2017; 13: 73–89.
[58] Benedetti F. Placebo effects: From the neurobiological paradigm to translational implications. Neuron 2014; 84(3): 623–637.
[59] Wager TD, Atlas LY, Leotti LA, Rilling JK. Predicting individual differences in placebo analgesia: Contributions of brain activity during anticipation and pain experience. J Neurosci 2011; 31(2): 439–452.
[60] Roy M, Shohamy D, Daw N, Jepma M, Wimmer GE, Wager TD. Representation of aversive prediction errors in the human periaqueductal gray. Nat Neurosci 2014; 17(11): 1607–1612.
[61] Roy M, Shohamy D, Wager TD. Ventromedial prefrontalsubcortical systems and the generation of affective meaning. Trends Cogn Sci 2012; 16(3): 147–156.
[62] White LK, Helfinstein SM, Reeb-Sutherland BC, Degnan KA, Fox NA. Role of attention in the regulation of fear and anxiety. Dev Neurosci 2009; 31(4): 309–317.
[63] Moseley GL. Whole of community pain education for back pain. Why does first-line care get almost no attention and what exactly are we waiting for? Br J Sports Med 2019; 53(10): 588–589.
[64] Bernstein IA, Malik Q, Carville S, Ward S. Low back pain and sciatica: Summary of NICE guidance. BMJ 2017; 356: 10–13.
[65] Harden RN, Oaklander AL, Burton AW, Perez RSGM, Richardson K, Swan M, et al. Complex regional pain syndrome: Practical diagnostic and treatment guidelines, 4th edition. Pain Med 2013; 14(2): 180–229.
[66] Lin I, Wiles L, Waller R, Goucke R, Nagree Y, Gibberd M, et al. What does best practice care for musculoskeletal pain look like? Eleven consistent recommendations from highquality clinical practice guidelines: Systematic review. Br J Sports Med 2020; 54(2): 79–86.
[67] Leake HB, Moseley GL, Stanton TR, O’Hagan ET, Heathcote LC. What do patients value learning about pain? A mixed-methods survey on the relevance of target concepts after pain science education. Pain 2021; 162(10): 2558–2568.
[68] Moseley G, Butler D. Explain pain supercharged. 1st ed. Adelaide: Noigroup publications; 2017.