Advertisement

Chronic Back Pain Is Associated With Decreased Prefrontal and Anterior Insular Gray Matter: Results From a Population-Based Cohort Study

Published:October 14, 2015DOI:https://doi.org/10.1016/j.jpain.2015.10.003

      Highlights

      • This work is a cohort study on brain gray matter changes in chronic back pain (CBP) applying voxel-based morphometry.
      • Patients with CBP showed decreased prefrontal and anterior insular gray matter.
      • Pain intensity was associated with a decrease in prefrontal and anterior cingulate cortex gray matter.

      Abstract

      Chronic back pain (CBP) is associated with circumscribed atrophy in gray matter (GM) predominantly localized in areas of the so-called pain matrix and the prefrontal cortex (PFC). Previous studies applying voxel-based morphometry (VBM) for identifying structural brain alterations related to CBP have reported inconsistent results, were limited to small sample sizes, and often did not control for medication. We therefore used VBM for high-resolution magnetic resonance images to investigate the association of CBP and regional GM volume in 111 individuals with CBP and 432 pain-free controls derived from the representative Study of Health in Pomerania, controlling for effects of medication. CBP was associated with decreased regional GM in the ventrolateral PFC and dorsolateral PFC, both the ventral and dorsal medial PFC, and the anterior insula. Pain intensity showed a weak negative correlation with GM volume in the left dorsolateral PFC, ventrolateral PFC, and anterior cingulate cortex. The CBP sample showed alterations in regions commonly associated with pain processing and emotional demands. To our knowledge, this is the first VBM study reporting decreased regional GM volume in the medial PFC in a CBP sample. We were unable to confirm alterations in regions other than the dorsolateral PFC and the insula.

      Perspective

      Previous studies reported inconsistent results for brain areas altered in chronic pain conditions, which may be in part attributable to small sample sizes, medication use, or emotional comorbidities. This study in a large and representative cohort helps to clarify these issues.

      Key words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic and Personal

      Subscribe:

      Subscribe to The Journal of Pain
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Apkarian A.V.
        • Baliki M.N.
        • Geha P.Y.
        Towards a theory of chronic pain.
        Prog Neurobiol. 2009; 87: 81-97
        • Apkarian A.V.
        • Hashmi J.A.
        • Baliki M.N.
        Pain and the brain: specificity and plasticity of the brain in clinical chronic pain.
        Pain. 2011; 152: S49-S64
        • Apkarian A.V.
        • Sosa Y.
        • Sonty S.
        • Levy R.M.
        • Harden R.N.
        • Parrish T.B.
        • Gitelman D.R.
        Chronic back pain is associated with decreased prefrontal and thalamic gray matter density.
        J Neurosci. 2004; 24: 10410-10415
        • Ashburner J.
        • Friston K.J.
        Voxel-based morphometry–the methods.
        Neuroimage. 2000; 11: 805-821
        • Baliki M.N.
        • Chialvo D.R.
        • Geha P.Y.
        • Levy R.M.
        • Harden R.N.
        • Parrish T.B.
        • Apkarian A.V.
        Chronic pain and the emotional brain: specific brain activity associated with spontaneous fluctuations of intensity of chronic back pain.
        J Neurosci. 2006; 26: 12165-12173
        • Baliki M.N.
        • Geha P.Y.
        • Apkarian A.V.
        Parsing pain perception between nociceptive representation and magnitude estimation.
        J Neurophysiol. 2009; 101: 875-887
        • 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. 2010; 66: 149-160
        • Baliki M.N.
        • Petre B.
        • Torbey S.
        • Herrmann K.M.
        • Huang L.
        • Schnitzer T.J.
        • Fields H.L.
        • Apkarian A.V.
        Corticostriatal functional connectivity predicts transition to chronic back pain.
        Nat Neurosci. 2012; 15: 1117-1119
        • Baliki M.N.
        • Schnitzer T.J.
        • Bauer W.R.
        • Apkarian A.V.
        Brain morphological signatures for chronic pain.
        PLoS One. 2011; 6: e26010
        • Bantick S.J.
        • Wise R.G.
        • Ploghaus A.
        • Clare S.
        • Smith S.M.
        • Tracey I.
        Imaging how attention modulates pain in humans using functional MRI.
        Brain. 2002; 125: 310-319
        • Barbey A.K.
        • Koenigs M.
        • Grafman J.
        Dorsolateral prefrontal contributions to human working memory.
        Cortex. 2013; 49: 1195-1205
        • Bingel U.
        • Tracey I.
        Imaging CNS modulation of pain in humans.
        Physiology. 2008; 23: 371-380
        • Bogdanov V.B.
        • Vigano A.
        • Noirhomme Q.
        • Bogdanova O.V.
        • Guy N.
        • Laureys S.
        • Renshaw P.F.
        • Dallel R.
        • Phillips C.
        • Schoenen J.
        Cerebral responses and role of the prefrontal cortex in conditioned pain modulation: an fMRI study in healthy subjects.
        Behav Brain Res. 2015; 281: 187-198
        • Buckalew N.
        • Haut M.W.
        • Morrow L.
        • Weiner D.
        Chronic pain is associated with brain volume loss in older adults: preliminary evidence.
        Pain Med. 2008; 9: 240-248
        • Costa Lda C.
        • Maher C.G.
        • McAuley J.H.
        • Hancock M.J.
        • Herbert R.D.
        • Refshauge K.M.
        • Henschke N.
        Prognosis for patients with chronic low back pain: inception cohort study.
        BMJ. 2009; 339: b3829
        • Craig A.D.
        Emotional moments across time: a possible neural basis for time perception in the anterior insula.
        Philos Trans R Soc Lond B Biol Sci. 2009; 364: 1933-1942
        • da C.M.C.L.
        • Maher C.G.
        • Hancock M.J.
        • McAuley J.H.
        • Herbert R.D.
        • Costa L.O.
        The prognosis of acute and persistent low-back pain: a meta-analysis.
        CMAJ. 2012; 184: E613-624
        • Dolman A.J.
        • Loggia M.L.
        • Edwards R.R.
        • Gollub R.L.
        • Kong J.
        • Napadow V.
        • Wasan A.D.
        Phenotype matters: the absence of a positive association between cortical thinning and chronic low back pain when controlling for salient clinical variables.
        Clin J Pain. 2014; 30: 839-845
        • Gu X.
        • Han S.
        Attention and reality constraints on the neural processes of empathy for pain.
        Neuroimage. 2007; 36: 256-267
        • Hadjipavlou G.
        • Dunckley P.
        • Behrens T.E.
        • Tracey I.
        Determining anatomical connectivities between cortical and brainstem pain processing regions in humans: a diffusion tensor imaging study in healthy controls.
        Pain. 2006; 123: 169-178
        • Harman K.
        • Ruyak P.
        Working through the pain: a controlled study of the impact of persistent pain on performing a computer task.
        Clin J Pain. 2005; 21: 216-222
        • Hashmi J.A.
        • Baliki M.N.
        • Huang L.
        • Baria A.T.
        • Torbey S.
        • Hermann K.M.
        • Schnitzer T.J.
        • Apkarian A.V.
        Shape shifting pain: chronification of back pain shifts brain representation from nociceptive to emotional circuits.
        Brain. 2013; 136: 2751-2768
        • Hegenscheid K.
        • Kuhn J.P.
        • Volzke H.
        • Biffar R.
        • Hosten N.
        • Puls R.
        Whole-body magnetic resonance imaging of healthy volunteers: pilot study results from the population-based SHIP study.
        Rofo. 2009; 181: 748-759
        • Hegenscheid K.
        • Seipel R.
        • Schmidt C.O.
        • Volzke H.
        • Kuhn J.P.
        • Biffar R.
        • Kroemer H.K.
        • Hosten N.
        • Puls R.
        Potentially relevant incidental findings on research whole-body MRI in the general adult population: frequencies and management.
        Eur Radiol. 2013; 23: 816-826
        • Henschke N.
        • Maher C.G.
        • Refshauge K.M.
        • Herbert R.D.
        • Cumming R.G.
        • Bleasel J.
        • York J.
        • Das A.
        • McAuley J.H.
        Prognosis in patients with recent onset low back pain in Australian primary care: inception cohort study.
        BMJ. 2008; 337: a171
        • Hoy D.
        • Bain C.
        • Williams G.
        • March L.
        • Brooks P.
        • Blyth F.
        • Woolf A.
        • Vos T.
        • Buchbinder R.
        A systematic review of the global prevalence of low back pain.
        Arthritis Rheum. 2012; 64: 2028-2037
        • IASP
        Classification of chronic pain. Descriptions of chronic pain syndromes and definitions of pain terms. Prepared by the International Association for the Study of Pain, Subcommittee on Taxonomy.
        Pain Suppl. 1986; 3: S1-S226
        • Isnard J.
        • Magnin M.
        • Jung J.
        • Mauguiere F.
        • Garcia-Larrea L.
        Does the insula tell our brain that we are in pain?.
        Pain. 2011; 152: 946-951
        • Ivo R.
        • Nicklas A.
        • Dargel J.
        • Sobottke R.
        • Delank K.S.
        • Eysel P.
        • Weber B.
        Brain structural and psychometric alterations in chronic low back pain.
        Eur Spine J. 2013; 22: 1958-1964
        • Jackson P.L.
        • Brunet E.
        • Meltzoff A.N.
        • Decety J.
        Empathy examined through the neural mechanisms involved in imagining how I feel versus how you feel pain.
        Neuropsychologia. 2006; 44: 752-761
        • Jackson P.L.
        • Meltzoff A.N.
        • Decety J.
        How do we perceive the pain of others? A window into the neural processes involved in empathy.
        Neuroimage. 2005; 24: 771-779
        • Lee D.M.
        • Pendleton N.
        • Tajar A.
        • O'Neill T.W.
        • O'Connor D.B.
        • Bartfai G.
        • Boonen S.
        • Casanueva F.F.
        • Finn J.D.
        • Forti G.
        • Giwercman A.
        • Han T.S.
        • Huhtaniemi I.T.
        • Kula K.
        • Lean M.E.
        • Punab M.
        • Silman A.J.
        • Vanderschueren D.
        • Moseley C.M.
        • Wu F.C.
        • McBeth J.
        • Group E.S.
        Chronic widespread pain is associated with slower cognitive processing speed in middle-aged and older European men.
        Pain. 2010; 151: 30-36
        • Legrain V.
        • Damme S.V.
        • Eccleston C.
        • Davis K.D.
        • Seminowicz D.A.
        • Crombez G.
        A neurocognitive model of attention to pain: behavioral and neuroimaging evidence.
        Pain. 2009; 144: 230-232
        • Lorenz J.
        • Cross D.J.
        • Minoshima S.
        • Morrow T.J.
        • Paulson P.E.
        • Casey K.L.
        A unique representation of heat allodynia in the human brain.
        Neuron. 2002; 35: 383-393
        • Lorenz J.
        • Minoshima S.
        • Casey K.L.
        Keeping pain out of mind: the role of the dorsolateral prefrontal cortex in pain modulation.
        Brain. 2003; 126: 1079-1091
        • Luerding R.
        • Weigand T.
        • Bogdahn U.
        • Schmidt-Wilcke T.
        Working memory performance is correlated with local brain morphology in the medial frontal and anterior cingulate cortex in fibromyalgia patients: structural correlates of pain-cognition interaction.
        Brain. 2008; 131: 3222-3231
        • 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. 2005; 25: 46-59
        • Phan K.L.
        • Wager T.
        • Taylor S.F.
        • Liberzon I.
        Functional neuroanatomy of emotion: a meta-analysis of emotion activation studies in PET and fMRI.
        Neuroimage. 2002; 16: 331-348
        • Porro C.A.
        • Baraldi P.
        • Pagnoni G.
        • Serafini M.
        • Facchin P.
        • Maieron M.
        • Nichelli P.
        Does anticipation of pain affect cortical nociceptive systems?.
        J Neurosci. 2002; 22: 3206-3214
        • Salomons T.V.
        • Johnstone T.
        • Backonja M.M.
        • Shackman A.J.
        • Davidson R.J.
        Individual differences in the effects of perceived controllability on pain perception: critical role of the prefrontal cortex.
        J Cogn Neurosci. 2007; 19: 993-1003
        • Schmidt-Wilcke T.
        • Leinisch E.
        • Ganssbauer S.
        • Draganski B.
        • Bogdahn U.
        • Altmeppen J.
        • May A.
        Affective components and intensity of pain correlate with structural differences in gray matter in chronic back pain patients.
        Pain. 2006; 125: 89-97
        • Seminowicz D.A.
        • Shpaner M.
        • Keaser M.L.
        • Krauthamer G.M.
        • Mantegna J.
        • Dumas J.A.
        • Newhouse P.A.
        • Filippi C.G.
        • Keefe F.J.
        • Naylor M.R.
        Cognitive-behavioral therapy increases prefrontal cortex gray matter in patients with chronic pain.
        J Pain. 2013; 14: 1573-1584
        • Seminowicz D.A.
        • Wideman T.H.
        • Naso L.
        • Hatami-Khoroushahi Z.
        • Fallatah S.
        • Ware M.A.
        • Jarzem P.
        • Bushnell M.C.
        • Shir Y.
        • Ouellet J.A.
        • Stone L.S.
        Effective treatment of chronic low back pain in humans reverses abnormal brain anatomy and function.
        J Neurosci. 2011; 31: 7540-7550
        • Stanton T.R.
        • Henschke N.
        • Maher C.G.
        • Refshauge K.M.
        • Latimer J.
        • McAuley J.H.
        After an episode of acute low back pain, recurrence is unpredictable and not as common as previously thought.
        Spine. 2008; 33: 2923-2928
        • Tzourio-Mazoyer N.
        • Landeau B.
        • Papathanassiou D.
        • Crivello F.
        • Etard O.
        • Delcroix N.
        • Mazoyer B.
        • Joliot M.
        Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain.
        Neuroimage. 2002; 15: 273-289
        • Volzke H.
        • Alte D.
        • Schmidt C.O.
        • Radke D.
        • Lorbeer R.
        • Friedrich N.
        • Aumann N.
        • Lau K.
        • Piontek M.
        • Born G.
        • Havemann C.
        • Ittermann T.
        • Schipf S.
        • Haring R.
        • Baumeister S.E.
        • Wallaschofski H.
        • Nauck M.
        • Frick S.
        • Arnold A.
        • Junger M.
        • Mayerle J.
        • Kraft M.
        • Lerch M.M.
        • Dorr M.
        • Reffelmann T.
        • Empen K.
        • Felix S.B.
        • Obst A.
        • Koch B.
        • Glaser S.
        • Ewert R.
        • Fietze I.
        • Penzel T.
        • Doren M.
        • Rathmann W.
        • Haerting J.
        • Hannemann M.
        • Ropcke J.
        • Schminke U.
        • Jurgens C.
        • Tost F.
        • Rettig R.
        • Kors J.A.
        • Ungerer S.
        • Hegenscheid K.
        • Kuhn J.P.
        • Kuhn J.
        • Hosten N.
        • Puls R.
        • Henke J.
        • Gloger O.
        • Teumer A.
        • Homuth G.
        • Volker U.
        • Schwahn C.
        • Holtfreter B.
        • Polzer I.
        • Kohlmann T.
        • Grabe H.J.
        • Rosskopf D.
        • Kroemer H.K.
        • Kocher T.
        • Biffar R.
        • John U.
        • Hoffmann W.
        Cohort profile: the study of health in Pomerania.
        Int J Epidemiol. 2011; 40: 294-307
        • Vos T.
        • Flaxman A.D.
        • Naghavi M.
        • Lozano R.
        • Michaud C.
        • Ezzati M.
        • Shibuya K.
        • Salomon J.A.
        • Abdalla S.
        • Aboyans V.
        • Abraham J.
        • Ackerman I.
        • Aggarwal R.
        • Ahn S.Y.
        • Ali M.K.
        • Alvarado M.
        • Anderson H.R.
        • Anderson L.M.
        • Andrews K.G.
        • Atkinson C.
        • Baddour L.M.
        • Bahalim A.N.
        • Barker-Collo S.
        • Barrero L.H.
        • Bartels D.H.
        • Basanez M.G.
        • Baxter A.
        • Bell M.L.
        • Benjamin E.J.
        • Bennett D.
        • Bernabe E.
        • Bhalla K.
        • Bhandari B.
        • Bikbov B.
        • Bin Abdulhak A.
        • Birbeck G.
        • Black J.A.
        • Blencowe H.
        • Blore J.D.
        • Blyth F.
        • Bolliger I.
        • Bonaventure A.
        • Boufous S.
        • Bourne R.
        • Boussinesq M.
        • Braithwaite T.
        • Brayne C.
        • Bridgett L.
        • Brooker S.
        • Brooks P.
        • Brugha T.S.
        • Bryan-Hancock C.
        • Bucello C.
        • Buchbinder R.
        • Buckle G.
        • Budke C.M.
        • Burch M.
        • Burney P.
        • Burstein R.
        • Calabria B.
        • Campbell B.
        • Canter C.E.
        • Carabin H.
        • Carapetis J.
        • Carmona L.
        • Cella C.
        • Charlson F.
        • Chen H.
        • Cheng A.T.
        • Chou D.
        • Chugh S.S.
        • Coffeng L.E.
        • Colan S.D.
        • Colquhoun S.
        • Colson K.E.
        • Condon J.
        • Connor M.D.
        • Cooper L.T.
        • Corriere M.
        • Cortinovis M.
        • de Vaccaro K.C.
        • Couser W.
        • Cowie B.C.
        • Criqui M.H.
        • Cross M.
        • Dabhadkar K.C.
        • Dahiya M.
        • Dahodwala N.
        • Damsere-Derry J.
        • Danaei G.
        • Davis A.
        • De Leo D.
        • Degenhardt L.
        • Dellavalle R.
        • Delossantos A.
        • Denenberg J.
        • Derrett S.
        • Des Jarlais D.C.
        • Dharmaratne S.D.
        • Dherani M.
        • Diaz-Torne C.
        • Dolk H.
        • Dorsey E.R.
        • Driscoll T.
        • Duber H.
        • Ebel B.
        • Edmond K.
        • Elbaz A.
        • Ali S.E.
        • Erskine H.
        • Erwin P.J.
        • Espindola P.
        • Ewoigbokhan S.E.
        • Farzadfar F.
        • Feigin V.
        • Felson D.T.
        • Ferrari A.
        • Ferri C.P.
        • Fevre E.M.
        • Finucane M.M.
        • Flaxman S.
        • Flood L.
        • Foreman K.
        • Forouzanfar M.H.
        • Fowkes F.G.
        • Franklin R.
        • Fransen M.
        • Freeman M.K.
        • Gabbe B.J.
        • Gabriel S.E.
        • Gakidou E.
        • Ganatra H.A.
        • Garcia B.
        • Gaspari F.
        • Gillum R.F.
        • Gmel G.
        • Gosselin R.
        • Grainger R.
        • Groeger J.
        • Guillemin F.
        • Gunnell D.
        • Gupta R.
        • Haagsma J.
        • Hagan H.
        • Halasa Y.A.
        • Hall W.
        • Haring D.
        • Haro J.M.
        • Harrison J.E.
        • Havmoeller R.
        • Hay R.J.
        • Higashi H.
        • Hill C.
        • Hoen B.
        • Hoffman H.
        • Hotez P.J.
        • Hoy D.
        • Huang J.J.
        • Ibeanusi S.E.
        • Jacobsen K.H.
        • James S.L.
        • Jarvis D.
        • Jasrasaria R.
        • Jayaraman S.
        • Johns N.
        • Jonas J.B.
        • Karthikeyan G.
        • Kassebaum N.
        • Kawakami N.
        • Keren A.
        • Khoo J.P.
        • King C.H.
        • Knowlton L.M.
        • Kobusingye O.
        • Koranteng A.
        • Krishnamurthi R.
        • Lalloo R.
        • Laslett L.L.
        • Lathlean T.
        • Leasher J.L.
        • Lee Y.Y.
        • Leigh J.
        • Lim S.S.
        • Limb E.
        • Lin J.K.
        • Lipnick M.
        • Lipshultz S.E.
        • Liu W.
        • Loane M.
        • Ohno S.L.
        • Lyons R.
        • Ma J.
        • Mabweijano J.
        • MacIntyre M.F.
        • Malekzadeh R.
        • Mallinger L.
        • Manivannan S.
        • Marcenes W.
        • March L.
        • Margolis D.J.
        • Marks G.B.
        • Marks R.
        • Matsumori A.
        • Matzopoulos R.
        • Mayosi B.M.
        • McAnulty J.H.
        • McDermott M.M.
        • McGill N.
        • McGrath J.
        • Medina-Mora M.E.
        • Meltzer M.
        • Mensah G.A.
        • Merriman T.R.
        • Meyer A.C.
        • Miglioli V.
        • Miller M.
        • Miller T.R.
        • Mitchell P.B.
        • Mocumbi A.O.
        • Moffitt T.E.
        • Mokdad A.A.
        • Monasta L.
        • Montico M.
        • Moradi-Lakeh M.
        • Moran A.
        • Morawska L.
        • Mori R.
        • Murdoch M.E.
        • Mwaniki M.K.
        • Naidoo K.
        • Nair M.N.
        • Naldi L.
        • Narayan K.M.
        • Nelson P.K.
        • Nelson R.G.
        • Nevitt M.C.
        • Newton C.R.
        • Nolte S.
        • Norman P.
        • Norman R.
        • O'Donnell M.
        • O'Hanlon S.
        • Olives C.
        • Omer S.B.
        • Ortblad K.
        • Osborne R.
        • Ozgediz D.
        • Page A.
        • Pahari B.
        • Pandian J.D.
        • Rivero A.P.
        • Patten S.B.
        • Pearce N.
        • Padilla R.P.
        • Perez-Ruiz F.
        • Perico N.
        • Pesudovs K.
        • Phillips D.
        • Phillips M.R.
        • Pierce K.
        • Pion S.
        • Polanczyk G.V.
        • Polinder S.
        • Pope 3rd, C.A.
        • Popova S.
        • Porrini E.
        • Pourmalek F.
        • Prince M.
        • Pullan R.L.
        • Ramaiah K.D.
        • Ranganathan D.
        • Razavi H.
        • Regan M.
        • Rehm J.T.
        • Rein D.B.
        • Remuzzi G.
        • Richardson K.
        • Rivara F.P.
        • Roberts T.
        • Robinson C.
        • De Leon F.R.
        • Ronfani L.
        • Room R.
        • Rosenfeld L.C.
        • Rushton L.
        • Sacco R.L.
        • Saha S.
        • Sampson U.
        • Sanchez-Riera L.
        • Sanman E.
        • Schwebel D.C.
        • Scott J.G.
        • Segui-Gomez M.
        • Shahraz S.
        • Shepard D.S.
        • Shin H.
        • Shivakoti R.
        • Singh D.
        • Singh G.M.
        • Singh J.A.
        • Singleton J.
        • Sleet D.A.
        • Sliwa K.
        • Smith E.
        • Smith J.L.
        • Stapelberg N.J.
        • Steer A.
        • Steiner T.
        • Stolk W.A.
        • Stovner L.J.
        • Sudfeld C.
        • Syed S.
        • Tamburlini G.
        • Tavakkoli M.
        • Taylor H.R.
        • Taylor J.A.
        • Taylor W.J.
        • Thomas B.
        • Thomson W.M.
        • Thurston G.D.
        • Tleyjeh I.M.
        • Tonelli M.
        • Towbin J.A.
        • Truelsen T.
        • Tsilimbaris M.K.
        • Ubeda C.
        • Undurraga E.A.
        • van der Werf M.J.
        • van Os J.
        • Vavilala M.S.
        • Venketasubramanian N.
        • Wang M.
        • Wang W.
        • Watt K.
        • Weatherall D.J.
        • Weinstock M.A.
        • Weintraub R.
        • Weisskopf M.G.
        • Weissman M.M.
        • White R.A.
        • Whiteford H.
        • Wiersma S.T.
        • Wilkinson J.D.
        • Williams H.C.
        • Williams S.R.
        • Witt E.
        • Wolfe F.
        • Woolf A.D.
        • Wulf S.
        • Yeh P.H.
        • Zaidi A.K.
        • Zheng Z.J.
        • Zonies D.
        • Lopez A.D.
        • Murray C.J.
        • AlMazroa M.A.
        • Memish Z.A.
        Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010.
        Lancet. 2012; 380: 2163-2196
        • Wiech K.
        • Farias M.
        • Kahane G.
        • Shackel N.
        • Tiede W.
        • Tracey I.
        An fMRI study measuring analgesia enhanced by religion as a belief system.
        Pain. 2008; 139: 467-476
        • Wiech K.
        • Kalisch R.
        • Weiskopf N.
        • Pleger B.
        • Stephan K.E.
        • Dolan R.J.
        Anterolateral prefrontal cortex mediates the analgesic effect of expected and perceived control over pain.
        J Neurosci. 2006; 26: 11501-11509
        • Younger J.W.
        • Chu L.F.
        • D'Arcy N.T.
        • Trott K.E.
        • Jastrzab L.E.
        • Mackey S.C.
        Prescription opioid analgesics rapidly change the human brain.
        Pain. 2011; 152: 1803-1810
        • Yu R.
        • Gollub R.L.
        • Spaeth R.
        • Napadow V.
        • Wasan A.
        • Kong J.
        Disrupted functional connectivity of the periaqueductal gray in chronic low back pain.
        Neuroimage Clin. 2014; 6: 100-108