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Brain regions associated with psychological pain: implications for a neural network and its relationship to physical pain

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Abstract

Research on brain areas involved in experiencing emotion and physical pain is abundant; however, psychological pain has received little attention in studies of the brain. The purpose of this systematic review was to provide an overview of studies on brain function related to psychological pain. The review was limited to studies in which participants experienced actual psychological pain or recalled a significant autobiographical event that may be assumed to have involved psychological pain. Based on results of the studies (N = 18), a tentative neural network for psychological pain is proposed that includes the thalamus, anterior and posterior cingulate cortex, the prefrontal cortex, cerebellum, and parahippocampal gyrus. Results indicated that grief may be a more accurate exemplar of psychological pain than recalled sadness, with indications of greater arousal during psychological pain. The proposed neural network for psychological pain overlaps to some extent with brain regions involved in physical pain, but results suggest a markedly reduced role for the insula, caudate, and putamen during psychological pain. Psychological pain is well known for its association with depression and as a precursor of suicidal behavior. Thus, identification of brain areas involved in psychological pain may help guide development of interventions to decrease mortality and morbidity.

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References

  • Apkarian, A. V., Bushnell, M. C., Treede, R. D., & Zubieta, J. K. (2005). Human brain mechanisms of pain perception and regulation in health and disease. European Journal of Pain, 9(4), 463–484. doi:10.1016/j.ejpain.2004.11.001.

    Article  PubMed  Google Scholar 

  • Apkarian, A. V., Baliki, M. N., & Geha, P. Y. (2009). Towards a theory of chronic pain. Progress in Neurobiology, 87(2), 81–97. doi:10.1016/j.pneurobio.2008.09.018.

    Article  PubMed  Google Scholar 

  • Biro, D. (2010). Is there such a thing as psychological pain? and why It matters. Culture, Medicine and Psychiatry. doi:10.1007/s11013-010-9190-y.

  • Borsook, D., Moulton, E. A., Tully, S., Schmahmann, J. D., & Becerra, L. (2008). Human cerebellar responses to brush and heat stimuli in healthy and neuropathic pain subjects. Cerebellum, 7(3), 252–272. doi:10.1007/s12311-008-0011-6.

    Article  PubMed  CAS  Google Scholar 

  • Bush, G., Luu, P., & Posner, M. I. (2000). Cognitive and emotional influences in anterior cingulate cortex. Trends in Cognitive Sciences, 4(6), 215–222.

    Article  PubMed  Google Scholar 

  • Chavez-Hernandez, A. M., Leenaars, A. A., Chavez-de Sanchez, M. I., & Leenaars, L. (2009). Suicide notes from Mexico and the United States: a thematic analysis. Salud Pública de México, 51(4), 314–320.

    Article  PubMed  Google Scholar 

  • Colibazzi, T., Posner, J., Wang, Z., Gorman, D., Gerber, A., Yu, S., et al. (2010). Neural systems subserving valence and arousal during the experience of induced emotions. Emotion, 10(3), 377–389. doi:10.1037/a0018484.

    Article  PubMed  Google Scholar 

  • Collins, D. L., Neelin, P., Peters, T. M., & Evans, A. C. (1994). Automatic 3D intersubject registration of MR volumetric data in standardized Talairach space. Journal of Computer Assisted Tomography, 18(2), 192–205.

    Article  PubMed  CAS  Google Scholar 

  • Davidson, R. J., & Irwin, W. (1999). The functional neuroanatomy of emotion and affective style. Trends in Cognitive Sciences, 3(1), 11–21.

    Article  PubMed  Google Scholar 

  • Drevets, W. C., & Raichle, M. E. (1998). Reciprocal suppression of regional cerebral blood flow during emotional versus higher cognitive processes: implications for interactions between emotion and cognition. Cognition and Emotion. Special Issue: Neuropsychological perspectives on affective and anxiety disorders, 12(3), 353–385.

    Google Scholar 

  • Eickhoff, S. B., Laird, A. R., Grefkes, C., Wang, L. E., Zilles, K., & Fox, P. T. (2009). Coordinate-based activation likelihood estimation meta-analysis of neuroimaging data: a random-effects approach based on empirical estimates of spatial uncertainty. Human Brain Mapping, 30(9), 2907–2926. doi:10.1002/hbm.20718.

    Article  PubMed  Google Scholar 

  • Eisenberger, N. I., Lieberman, M. D., & Williams, K. D. (2003). Does rejection hurt? An FMRI study of social exclusion. Science, 302(5643), 290–292. doi:10.1126/science.1089134.

    Article  PubMed  CAS  Google Scholar 

  • Friston, K. J., Holmes, A. P., Worsley, K. J., Poline, J. B., Frith, C. D., & Frackowiak, R. S. J. (1995). Statistical parametric maps in functional imaging: a general linear approach. Human Brain Mapping, 2(4), 189–210.

    Article  Google Scholar 

  • George, M. S., Ketter, T. A., Parekh, P. I., Herscovitch, P., & Post, R. M. (1996). Gender differences in regional cerebral blood flow during transient self-induced sadness or happiness. Biological Psychiatry, 40(9), 859–871. doi:10.1016/0006-3223(95)00572-2.

    Article  PubMed  CAS  Google Scholar 

  • Gerber, A. J., Posner, J., Gorman, D., Colibazzi, T., Yu, S., Wang, Z., et al. (2008). An affective circumplex model of neural systems subserving valence, arousal, and cognitive overlay during the appraisal of emotional faces. Neuropsychologia, 46(8), 2129–2139. doi:10.1016/j.neuropsychologia.2008.02.032.

    Article  PubMed  Google Scholar 

  • Gündel, H., O’Connor, M. F., Littrell, L., Fort, C., & Lane, R. D. (2003). Functional neuroanatomy of grief: an FMRI study. The American Journal of Psychiatry, 160(11), 1946–1953.

    Article  PubMed  Google Scholar 

  • Hilz, M. J., Devinsky, O., Szczepanska, H., Borod, J. C., Marthol, H., & Tutaj, M. (2006). Right ventromedial prefrontal lesions result in paradoxical cardiovascular activation with emotional stimuli. Brain, 129(Pt 12), 3343–3355. doi:10.1093/brain/awl299.

    Article  PubMed  Google Scholar 

  • Hudson, A. J. (2000). Pain perception and response: central nervous system mechanisms. Canadian Journal of Neurological Sciences, 27(1), 2–16.

    PubMed  CAS  Google Scholar 

  • Keedwell, P. A., Andrew, C., Williams, S. C., Brammer, M. J., & Phillips, M. L. (2005). A double dissociation of ventromedial prefrontal cortical responses to sad and happy stimuli in depressed and healthy individuals. Biological Psychiatry, 58(6), 495–503. doi:10.1016/j.biopsych.2005.04.035.

    Article  PubMed  Google Scholar 

  • Kersting, A., Ohrmann, P., Pedersen, A., Kroker, K., Samberg, D., Bauer, J., et al. (2009). Neural activation underlying acute grief in women after the loss of an unborn child. The American Journal of Psychiatry, 166(12), 1402–1410. doi:10.1176/appi.ajp.2009.08121875.

    Article  PubMed  Google Scholar 

  • Kilpatrick, L., & Cahill, L. (2003). Amygdala modulation of parahippocampal and frontal regions during emotionally influenced memory storage. NeuroImage, 20(4), 2091–2099.

    Article  PubMed  Google Scholar 

  • Lancaster, J. L., Rainey, L. H., Summerlin, J. L., Freitas, C. S., Fox, P. T., Evans, A. C., et al. (1997). Automated labeling of the human brain: a preliminary report on the development and evaluation of a forward-transform method. Human Brain Mapping, 5(4), 238–242. doi:10.1002/(SICI)1097-0193(1997)5:4<238::AID-HBM6>3.0.CO;2-4.

    Article  PubMed  CAS  Google Scholar 

  • Lancaster, J. L., Woldorff, M. G., Parsons, L. M., Liotti, M., Freitas, C. S., Rainey, L., et al. (2000). Automated Talairach atlas labels for functional brain mapping. Human Brain Mapping, 10(3), 120–131. doi:10.1002/1097-0193(200007)10:3<120::AID-HBM30>3.0.CO;2-8.

    Article  PubMed  CAS  Google Scholar 

  • Lane, R. D., Reiman, E. M., Ahern, G. L., Schwartz, G. E., & Davidson, R. J. (1997). Neuroanatomical correlates of happiness, sadness, and disgust. The American Journal of Psychiatry, 154(7), 926–933.

    PubMed  CAS  Google Scholar 

  • Liotti, M., Mayberg, H. S., McGinnis, S., Brannan, S. L., & Jerabek, P. (2002). Unmasking disease-specific cerebral blood flow abnormalities: mood challenge in patients with remitted unipolar depression. The American Journal of Psychiatry, 159(11), 1830–1840.

    Article  PubMed  Google Scholar 

  • Macdonald, G., & Leary, M. R. (2005). Why does social exclusion hurt? The relationship between social and physical pain. Psychological Bulletin, 131(2), 202–223. doi:10.1037/0033-2909.131.2.202.

    Article  PubMed  Google Scholar 

  • Martin, M. (1990). On the induction of mood. Clinical Psychology Review, 10(6), 669–697.

    Article  Google Scholar 

  • Mee, S., Bunney, B. G., Reist, C., Potkin, S. G., & Bunney, W. E. (2006). Psychological pain: a review of evidence. Journal of Psychiatric Research, 40(8), 680–690. doi:10.1016/j.jpsychires.2006.03.003.

    Article  PubMed  Google Scholar 

  • Mee, S., Bunney, B. G., Bunney, W. E., Hetrick, W., Potkin, S. G., & Reist, C. (2011). Assessment of psychological pain in major depressive episodes. Journal of Psychiatric Research, 45(11), 1504–1510. doi:10.1016/j.jpsychires.2011.06.011.

    Article  PubMed  Google Scholar 

  • Meerwijk, E. L., & Weiss, S. J. (2011). Toward a unifying definition of psychological pain. Journal of Loss & Trauma, 16(5), 402–412, doi:10.1080/15325024.2011.572044.

    Google Scholar 

  • Moulton, E. A., Elman, I., Pendse, G., Schmahmann, J., Becerra, L., & Borsook, D. (2011). Aversion-related circuitry in the cerebellum: responses to noxious heat and unpleasant images. Journal of Neuroscience, 31(10), 3795–3804. doi:10.1523/JNEUROSCI.6709-10.2011.

    Article  PubMed  CAS  Google Scholar 

  • Munro, B. H. (2005). Statistical methods for health care research (5th ed.). Philadelphia, PA: Lippincott Williams & Wilkins.

    Google Scholar 

  • Murray, H. A. (2008). Explorations in personality (70th ed.). New York, NY: Oxford University Press.

    Google Scholar 

  • Najib, A., Lorberbaum, J. P., Kose, S., Bohning, D. E., & George, M. S. (2004). Regional brain activity in women grieving a romantic relationship breakup. The American Journal of Psychiatry, 161(12), 2245–2256. doi:10.1176/appi.ajp.161.12.2245.

    Article  PubMed  Google Scholar 

  • Nielen, M. M., Heslenfeld, D. J., Heinen, K., Van Strien, J. W., Witter, M. P., Jonker, C., et al. (2009). Distinct brain systems underlie the processing of valence and arousal of affective pictures. Brain and Cognition, 71(3), 387–396. doi:10.1016/j.bandc.2009.05.007.

    Article  PubMed  CAS  Google Scholar 

  • O’Connor, M. F., Gündel, H., McRae, K., & Lane, R. D. (2007). Baseline vagal tone predicts BOLD response during elicitation of grief. Neuropsychopharmacology, 32(10), 2184–2189. doi:10.1038/sj.npp.1301342.

    Article  PubMed  Google Scholar 

  • O’Connor, M. F., Wellisch, D. K., Stanton, A. L., Eisenberger, N. I., Irwin, M. R., & Lieberman, M. D. (2008). Craving love? Enduring grief activates brain’s reward center. NeuroImage, 42(2), 969–972. doi:10.1016/j.neuroimage.2008.04.256.

    Article  PubMed  Google Scholar 

  • Olié, E., Guillaume, S., Jaussent, I., Courtet, P., & Jollant, F. (2010). Higher psychological pain during a major depressive episode may be a factor of vulnerability to suicidal ideation and act. Journal of Affective Disorders, 120(1–3), 226–230. doi:10.1016/j.jad.2009.03.013.

    Article  PubMed  Google Scholar 

  • Onoda, K., Okamoto, Y., Nakashima, K., Nittono, H., Ura, M., & Yamawaki, S. (2009). Decreased ventral anterior cingulate cortex activity is associated with reduced social pain during emotional support. Social Neuroscience, 4(5), 443–454. doi:10.1080/17470910902955884.

    Article  PubMed  Google Scholar 

  • Orbach, I., Mikulincer, M., Gilboa-Schechtman, E., & Sirota, P. (2003). Mental pain and its relationship to suicidality and life meaning. Suicide & Life-Threatening Behavior, 33(3), 231–241.

    Article  Google Scholar 

  • Orbach, I., Mikulincer, M., Sirota, P., & Gilboa-Schechtman, E. (2003). Mental pain: a multidimensional operationalization and definition. Suicide & Life-Threatening Behavior, 33(3), 219–230.

    Article  Google Scholar 

  • Pardo, J. V., Pardo, P. J., & Raichle, M. E. (1993). Neural correlates of self-induced dysphoria. The American Journal of Psychiatry, 150(5), 713–719.

    PubMed  CAS  Google Scholar 

  • Pelletier, M., Bouthillier, A., Levesque, J., Carrier, S., Breault, C., Paquette, V., et al. (2003). Separate neural circuits for primary emotions? Brain activity during self-induced sadness and happiness in professional actors. Neuroreport, 14(8), 1111–1116. doi:10.1097/01.wnr.0000075421.59944.69.

    Article  PubMed  Google Scholar 

  • Phan, K. L., Wager, T., Taylor, S. F., & Liberzon, I. (2002). Functional neuroanatomy of emotion: a meta-analysis of emotion activation studies in PET and fMRI. NeuroImage, 16(2), 331–348. doi:10.1006/nimg.2002.1087.

    Article  PubMed  Google Scholar 

  • Pompili, M., Lester, D., Leenaars, A. A., Tatarelli, R., & Girardi, P. (2008). Psychache and suicide: a preliminary investigation. Suicide & Life-Threatening Behavior, 38(1), 116–121.

    Article  Google Scholar 

  • Price, D. D. (2000). Psychological and neural mechanisms of the affective dimension of pain. Science, 288(5472), 1769–1772.

    Article  PubMed  CAS  Google Scholar 

  • Prince, M., Patel, V., Saxena, S., Maj, M., Maselko, J., Phillips, M. R., et al. (2007). No health without mental health. Lancet, 370(9590), 859–877. doi:10.1016/S0140-6736(07)61238-0.

    Article  PubMed  Google Scholar 

  • Ramnani, N. (2006). The primate cortico-cerebellar system: anatomy and function. Nature Reviews Neuroscience, 7(7), 511–522. doi:10.1038/nrn1953.

    Article  PubMed  CAS  Google Scholar 

  • Reisch, T., Seifritz, E., Esposito, F., Wiest, R., Valach, L., & Michel, K. (2010). An fMRI study on mental pain and suicidal behavior. Journal of Affective Disorders. doi:10.1016/j.jad.2010.03.005.

  • Sackeim, H. A., Greenberg, M. S., Weiman, A. L., Gur, R. C., Hungerbuhler, J. P., & Geschwind, N. (1982). Hemispheric asymmetry in the expression of positive and negative emotions. Neurologic evidence. Archives of Neurology, 39(4), 210–218.

    Article  PubMed  CAS  Google Scholar 

  • Schmahl, C. G., Vermetten, E., Elzinga, B. M., & Bremner, J. D. (2004). A positron emission tomography study of memories of childhood abuse in borderline personality disorder. Biological Psychiatry, 55(7), 759–765. doi:10.1016/j.biopsych.2003.11.007.

    Article  PubMed  Google Scholar 

  • Schmahmann, J. D. (2004). Disorders of the cerebellum: ataxia, dysmetria of thought, and the cerebellar cognitive affective syndrome. The Journal of Neuropsychiatry and Clinical Neurosciences, 16(3), 367–378. doi:10.1176/appi.neuropsych.16.3.367.

    Article  PubMed  Google Scholar 

  • Schmahmann, J. D., & Pandya, D. N. (1997). The cerebrocerebellar system. International Review of Neurobiology, 41, 31–60.

    Article  PubMed  CAS  Google Scholar 

  • Schnitzler, A., & Ploner, M. (2000). Neurophysiology and functional neuroanatomy of pain perception. Journal of Clinical Neurophysiology, 17(6), 592–603.

    Article  PubMed  CAS  Google Scholar 

  • Sergent, J. (1994). Brain-imaging studies of cognitive functions. Trends in Neurosciences, 17(6), 221–227.

    Article  PubMed  CAS  Google Scholar 

  • Shackman, A. J., Salomons, T. V., Slagter, H. A., Fox, A. S., Winter, J. J., & Davidson, R. J. (2011). The integration of negative affect, pain and cognitive control in the cingulate cortex. Nature Reviews Neuroscience, 12(3), 154–167. doi:10.1038/nrn2994.

    Article  PubMed  CAS  Google Scholar 

  • Sherwood, L. (2010). Human physiology: from cells to systems (7th ed.). Belmont, CA: Cengage Learning.

    Google Scholar 

  • Shneidman, E. S. (1998). Perspectives on suicidology: further reflections on suicide and psychache. Suicide & Life-Threatening Behavior, 28(3), 245–250.

    CAS  Google Scholar 

  • Soumani, A., Damigos, D., Oulis, P., Masdrakis, V., Ploumpidis, D., Mavreas, V., et al. (2011). Mental pain and suicide risk: application of the greek version of the Mental Pain and the Tolerance of Mental Pain scale. Psychiatriki, 22(4), 330–340.

    PubMed  CAS  Google Scholar 

  • Strotzer, M. (2009). One century of brain mapping using Brodmann areas. Klinische Neuroradiologie, 19(3), 179–186. doi:10.1007/s00062-009-9002-3.

    Article  PubMed  Google Scholar 

  • Talairach, J., & Tournoux, P. (1988). Co-planar stereotaxic atlas of the human brain. 3-dimensional proportional system: an approach to cerebral imaging. New York: Thieme. Thieme Classics.

    Google Scholar 

  • Tanida, M., Sakatani, K., Takano, R., & Tagai, K. (2004). Relation between asymmetry of prefrontal cortex activities and the autonomic nervous system during a mental arithmetic task: near infrared spectroscopy study. Neuroscience Letters, 369(1), 69–74. doi:10.1016/j.neulet.2004.07.076.

    Article  PubMed  CAS  Google Scholar 

  • Troister, T., & Holden, R. R. (2010). Comparing psychache, depression, and hopelessness in their associations with suicidality: a test of Shneidman’s theory of suicide. Personality and Individual Differences, 49(7), 689–693. doi:10.1016/j.paid.2010.06.006.

    Article  Google Scholar 

  • Tucker, D. M. (1981). Lateral brain function, emotion, and conceptualization. Psychological Bulletin, 89(1), 19–46.

    Article  PubMed  CAS  Google Scholar 

  • van Heeringen, K., Van den Abbeele, D., Vervaet, M., Soenen, L., & Audenaert, K. (2010). The functional neuroanatomy of mental pain in depression. Psychiatry Research. doi:10.1016/j.pscychresns.2009.07.011.

  • Vogt, B. A. (2005). Pain and emotion interactions in subregions of the cingulate gyrus. Nature Reviews Neuroscience, 6(7), 533–544. doi:10.1038/nrn1704.

    Article  PubMed  CAS  Google Scholar 

  • Wager, T. D., Phan, K. L., Liberzon, I., & Taylor, S. F. (2003). Valence, gender, and lateralization of functional brain anatomy in emotion: a meta-analysis of findings from neuroimaging. NeuroImage, 19(3), 513–531.

    Article  PubMed  Google Scholar 

  • Weiss, S. J., Haber, J., Horowitz, J. A., Stuart, G. W., & Wolfe, B. (2009). The inextricable nature of mental and physical health: implications for integrative care. Journal of the American Psychiatric Nurses Association, 15(6), 371–382. doi:10.1177/1078390309352513.

    Article  PubMed  Google Scholar 

  • Wolf, U., Rapoport, M. J., & Schweizer, T. A. (2009). Evaluating the affective component of the cerebellar cognitive affective syndrome. The Journal of Neuropsychiatry and Clinical Neurosciences, 21(3), 245–253. doi:10.1176/appi.neuropsych.21.3.245.

    Article  PubMed  Google Scholar 

  • Yakusheva, T. A., Shaikh, A. G., Green, A. M., Blazquez, P. M., Dickman, J. D., & Angelaki, D. E. (2007). Purkinje cells in posterior cerebellar vermis encode motion in an inertial reference frame. Neuron, 54(6), 973–985. doi:10.1016/j.neuron.2007.06.003.

    Article  PubMed  CAS  Google Scholar 

  • Zubieta, J. K., Ketter, T. A., Bueller, J. A., Xu, Y., Kilbourn, M. R., Young, E. A., et al. (2003). Regulation of human affective responses by anterior cingulate and limbic mu-opioid neurotransmission. Archives of General Psychiatry, 60(11), 1145–1153. doi:10.1001/archpsyc.60.11.1145.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Community Health Systems, University of California, San Francisco, San Francisco, CA, USA

    Esther L. Meerwijk & Sandra J. Weiss

  2. Department of Psychiatry, University of California, San Francisco, San Francisco, CA, USA

    Judith M. Ford

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  1. Esther L. Meerwijk
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Correspondence to Esther L. Meerwijk.

Appendix

Appendix

The following tables show areas of changed brain activity during the experience of psychological pain (PP), as implicated by 18 studies included in this review. Results for each study are shown for the study condition in which higher intensity of psychological pain was expected (e.g. higher vs. lower psychological pain, complicated grief vs. noncomplicated grief, sadness vs. neutral mood). The brain areas are non-overlapping and organized under the left and right hemispheres and subcortical medial areas. Green cells in the table indicate increased activity and red cells indicate decreased activity. Dotted cells indicate that a study reported a global brain area, whereas other studies may have distinguished subdivisions.

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Meerwijk, E.L., Ford, J.M. & Weiss, S.J. Brain regions associated with psychological pain: implications for a neural network and its relationship to physical pain. Brain Imaging and Behavior 7, 1–14 (2013). https://doi.org/10.1007/s11682-012-9179-y

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