Mental Health Comorbidities in Pediatric Chronic Pain: A Narrative Review of Epidemiology, Models, Neurobiological Mechanisms and Treatment

Jillian Vinall, Maria Pavlova, Gordon J G Asmundson, Nivez Rasic, Melanie Noel, Jillian Vinall, Maria Pavlova, Gordon J G Asmundson, Nivez Rasic, Melanie Noel

Abstract

Chronic pain during childhood and adolescence can lead to persistent pain problems and mental health disorders into adulthood. Posttraumatic stress disorders and depressive and anxiety disorders are mental health conditions that co-occur at high rates in both adolescent and adult samples, and are linked to heightened impairment and disability. Comorbid chronic pain and psychopathology has been explained by the presence of shared neurobiology and mutually maintaining cognitive-affective and behavioral factors that lead to the development and/or maintenance of both conditions. Particularly within the pediatric chronic pain population, these factors are embedded within the broader context of the parent-child relationship. In this review, we will explore the epidemiology of, and current working models explaining, these comorbidities. Particular emphasis will be made on shared neurobiological mechanisms, given that the majority of previous research to date has centered on cognitive, affective, and behavioral mechanisms. Parental contributions to co-occurring chronic pain and psychopathology in childhood and adolescence will be discussed. Moreover, we will review current treatment recommendations and future directions for both research and practice. We argue that the integration of biological and behavioral approaches will be critical to sufficiently address why these comorbidities exist and how they can best be targeted in treatment.

Keywords: anxiety; brain; chronic pain; comorbidity; depression; intervention; neurobiology; parent; posttraumatic stress disorder; stress.

Conflict of interest statement

The authors declare no conflict of interest. The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.

Figures

Figure 1
Figure 1
Possible mechanisms underlying the shared vulnerability and mutual maintenance of pediatric chronic pain and internalizing mental health disorders. 5-HTTLPR: Serotonin-transporter-linked polymorphic region; BDNF: Brain-derived neurotrophic factor; HPA: hypothalamic–pituitary–adrenal; S allele: Short allele.

References

    1. King S., Chambers C.T., Huguet A., MacNevin R.C., McGrath P.J., Parker L., MacDonald A.J. The epidemiology of chronic pain in children and adolescents revisited: A systematic review. Pain. 2011;152:2729–2738. doi: 10.1016/j.pain.2011.07.016.
    1. Groenewald C.B., Essner B.S., Wright D., Fesinmeyer M.D., Palermo T.M. The economic costs of chronic pain among a cohort of treatment-seeking adolescents in the united states. J. Pain. 2014;15:925–933. doi: 10.1016/j.jpain.2014.06.002.
    1. Fearon P., Hotopf M. Relation between headache in childhood and physical and psychiatric symptoms in adulthood: National birth cohort study. BMJ. 2001;322:1145. doi: 10.1136/bmj.322.7295.1145.
    1. Shelby G.D., Shirkey K.C., Sherman A.L., Beck J.E., Haman K., Shears A.R., Horst S.N., Smith C.A., Garber J., Walker L.S. Functional abdominal pain in childhood and long-term vulnerability to anxiety disorders. Pediatrics. 2013;132:475–482. doi: 10.1542/peds.2012-2191.
    1. Hotopf M., Carr S., Mayou R., Wadsworth M., Wessely S. Why do children have chronic abdominal pain, and what happens to them when they grow up? Population based cohort study. BMJ. 1998;316:1196–1200. doi: 10.1136/bmj.316.7139.1196.
    1. Asmundson G.J., Coons M.J., Taylor S., Katz J. Ptsd and the experience of pain: Research and clinical implications of shared vulnerability and mutual maintenance models. Can. J. Psychiatry. 2002;47:930–937.
    1. Asmundson G.J., Katz J. Understanding the co-occurrence of anxiety disorders and chronic pain: State-of-the-art. Depress. Anxiety. 2009;26:888–901. doi: 10.1002/da.20600.
    1. Sharp T.J., Harvey A.G. Chronic pain and posttraumatic stress disorder: Mutual maintenance? Clin. Psychol. Rev. 2001;21:857–877. doi: 10.1016/S0272-7358(00)00071-4.
    1. Asmundson G.J. The emotional and physical pains of trauma: Contemporary and innovative approaches for treating co-occurring ptsd and chronic pain. Depress. Anxiety. 2014;31:717–720. doi: 10.1002/da.22285.
    1. Eccleston C. Systematic review and meta-analysis of psychological therapies for children with chronic pain. Clin. Pract. Pediatr. Psychol. 2014;39:763–782.
    1. Shipton E.A. The transition from acute to chronic post surgical pain. Anaesth. Intensive Care. 2011;39:824–836.
    1. Groenewald C.B., Wright D.R., Palermo T.M. Health care expenditures associated with pediatric pain-related conditions in the united states. Pain. 2015;156:951–957. doi: 10.1097/j.pain.0000000000000137.
    1. Palermo T.M. Impact of recurrent and chronic pain on child and family daily functioning: A critical review of the literature. J. Dev. Behav. Pediatr. 2000;21:58–69. doi: 10.1097/00004703-200002000-00011.
    1. Egger H.L., Angold A., Costello E.J. Headaches and psychopathology in children and adolescents. J. Am. Acad. Child Adolesc. Psychiatry. 1998;37:951–958. doi: 10.1097/00004583-199809000-00015.
    1. Egger H.L., Costello E.J., Erkanli A., Angold A. Somatic complaints and psychopathology in children and adolescents: Stomach aches, musculoskeletal pains, and headaches. J. Am. Acad. Child Adolesc. Psychiatry. 1999;38:852–860.
    1. Walker L.S., Sherman A.L., Bruehl S., Garber J., Smith C.A. Functional abdominal pain patient subtypes in childhood predict functional gastrointestinal disorders with chronic pain and psychiatric comorbidities in adolescence and adulthood. Pain. 2012;153:1798–1806. doi: 10.1016/j.pain.2012.03.026.
    1. Shanahan L., Zucker N., Copeland W.E., Bondy C.L., Egger H.L., Costello E.J. Childhood somatic complaints predict generalized anxiety and depressive disorders during young adulthood in a community sample. Psychol. Med. 2015;45:1721–1730. doi: 10.1017/S0033291714002840.
    1. Noel M., Groenewald C.B., Beals-Erickson S.E., Gebert J.T., Palermo T.M. Chronic pain in adolescence and internalizing mental health disorders: A nationally representative study. Pain. 2016;157:1333–1338. doi: 10.1097/j.pain.0000000000000522.
    1. Balottin U., Fusar Poli P., Termine C., Molteni S., Galli F. Psychopathological symptoms in child and adolescent migraine and tension-type headache: A meta-analysis. Cephalalgia. 2013;33:112–122. doi: 10.1177/0333102412468386.
    1. Blaauw B.A., Dyb G., Hagen K., Holmen T.L., Linde M., Wentzel-Larsen T., Zwart J.A. Anxiety, depression and behavioral problems among adolescents with recurrent headache: The young-hunt study. J. Headache Pain. 2014;15:38. doi: 10.1186/1129-2377-15-38.
    1. Coffelt T.A., Bauer B.D., Carroll A.E. Inpatient characteristics of the child admitted with chronic pain. Pediatrics. 2013;132:e422–e429. doi: 10.1542/peds.2012-1739.
    1. Noel M., Beals-Erickson S.E., Law E.F., Alberts N., Palermo T.M. Characterizing the pain narratives of parents of youth with chronic pain. Clin. J. Pain. 2016;32:849–858. doi: 10.1097/AJP.0000000000000346.
    1. Simons L.E., Sieberg C.B., Claar R.L. Anxiety and functional disability in a large sample of children and adolescents with chronic pain. Pain Res. Manag. 2012;17:93–97. doi: 10.1155/2012/420676.
    1. Tegethoff M., Belardi A., Stalujanis E., Meinlschmidt G. Comorbidity of mental disorders and chronic pain: Chronology of onset in adolescents of a national representative cohort. J. Pain. 2015;16:1054–1064. doi: 10.1016/j.jpain.2015.06.009.
    1. Noel M., Wilson A.C., Holley A.L., Durkin L., Patton M., Palermo T.M. Posttraumatic stress disorder symptoms in youth with versus without chronic pain. Pain. 2016;157:2277–2284. doi: 10.1097/j.pain.0000000000000642.
    1. Korterink J.J., Diederen K., Benninga M.A., Tabbers M.M. Epidemiology of pediatric functional abdominal pain disorders: A meta-analysis. PLoS ONE. 2015;10:e0126982. doi: 10.1371/journal.pone.0126982.
    1. Egger H.L., Costello E.J., Erkanli A., Angold A. Somatic complaints and psychopathology in children and adolescents: Stomach aches, musculoskeletal pains, and headaches. J. Am. Acad. Child Adolesc. Psychiatry. 1999;38:852–860. doi: 10.1097/00004583-199907000-00015.
    1. Liedl A., Knaevelsrud C. Chronic pain and PTSD: The perpetual avoidance model and its treatment implications. Torture. 2008;18:69–76.
    1. Norman S.B., Stein M.B., Dimsdale J.E., Hoyt D.B. Pain in the aftermath of trauma is a risk factor for post-traumatic stress disorder. Psychol. Med. 2008;38:533–542. doi: 10.1017/S0033291707001389.
    1. Brown E.A., Kenardy J.A., Dow B.L. Ptsd perpetuates pain in children with traumatic brain injury. J. Pediatr. Psychol. 2014;39:512–520. doi: 10.1093/jpepsy/jsu014.
    1. Holley A.L., Wilson A.C., Noel M., Palermo T.M. Post-traumatic stress symptoms in children and adolescents with chronic pain: A topical review of the literature and a proposed framework for future research. Eur. J. Pain. 2016;20:1371–1383. doi: 10.1002/ejp.879.
    1. Chrousos G.P. Stress and disorders of the stress system. Nat. Rev. Endocrinol. 2009;5:374–381. doi: 10.1038/nrendo.2009.106.
    1. Francis D.D., Champagne F.A., Liu D., Meaney M.J. Maternal care, gene expression, and the development of individual differences in stress reactivity. Ann. N. Y. Acad. Sci. 1999;896:66–84. doi: 10.1111/j.1749-6632.1999.tb08106.x.
    1. Gunnar M., Quevedo K. The neurobiology of stress and development. Annu. Rev. Psychol. 2007;58:145–173. doi: 10.1146/annurev.psych.58.110405.085605.
    1. Heim C., Nemeroff C.B. The role of childhood trauma in the neurobiology of mood and anxiety disorders: Preclinical and clinical studies. Biol. Psychiatry. 2001;49:1023–1039. doi: 10.1016/S0006-3223(01)01157-X.
    1. Peters K.L. Neonatal stress reactivity and cortisol. J. Perinat. Neonatal Nurs. 1998;11:45–59. doi: 10.1097/00005237-199803000-00007.
    1. Shanks N., Harbuz M.S., Jessop D.S., Perks P., Moore P.M., Lightman S.L. Inflammatory disease as chronic stress. Ann. N. Y. Acad. Sci. 1998;840:599–607. doi: 10.1111/j.1749-6632.1998.tb09599.x.
    1. Lentjes E.G., Griep E.N., Boersma J.W., Romijn F.P., de Kloet E.R. Glucocorticoid receptors, fibromyalgia and low back pain. Psychoneuroendocrinology. 1997;22:603–614. doi: 10.1016/S0306-4530(97)00061-9.
    1. Heim C., Ehlert U., Hanker J.P., Hellhammer D.H. Abuse-related posttraumatic stress disorder and alterations of the hypothalamic-pituitary-adrenal axis in women with chronic pelvic pain. Psychosom. Med. 1998;60:309–318. doi: 10.1097/00006842-199805000-00017.
    1. Blumer D., Zorick F., Heilbronn M., Roth T. Biological markers for depression in chronic pain. J. Nerv. Ment. Dis. 1982;170:425–428. doi: 10.1097/00005053-198207000-00010.
    1. Tennant F., Hermann L. Normalization of serum cortisol concentration with opioid treatment of severe chronic pain. Pain Med. 2002;3:132–134. doi: 10.1046/j.1526-4637.2002.02019.x.
    1. Geiss A., Varadi E., Steinbach K., Bauer H.W., Anton F. Psychoneuroimmunological correlates of persisting sciatic pain in patients who underwent discectomy. Neurosci. Lett. 1997;237:65–68. doi: 10.1016/S0304-3940(97)00810-0.
    1. Griep E.N., Boersma J.W., Lentjes E.G., Prins A.P., van der Korst J.K., de Kloet E.R. Function of the hypothalamic-pituitary-adrenal axis in patients with fibromyalgia and low back pain. J. Rheumatol. 1998;25:1374–1381.
    1. Korszun A., Young E.A., Singer K., Carlson N.E., Brown M.B., Crofford L. Basal circadian cortisol secretion in women with temporomandibular disorders. J. Dent. Res. 2002;81:279–283. doi: 10.1177/154405910208100411.
    1. Blackburn-Munro G., Blackburn-Munro R.E. Chronic pain, chronic stress and depression: Coincidence or consequence? J. Neuroendocrinol. 2001;13:1009–1023. doi: 10.1046/j.0007-1331.2001.00727.x.
    1. Yehuda R. Biology of posttraumatic stress disorder. J. Clin. Psychiatry. 2001;62(Suppl. 17):41–46.
    1. Boyer P. Do anxiety and depression have a common pathophysiological mechanism? Acta Psychiatr. Scand. Suppl. 2000:24–29. doi: 10.1111/j.0065-1591.2000.acp29-04.x.
    1. Levitt N.S., Lindsay R.S., Holmes M.C., Seckl J.R. Dexamethasone in the last week of pregnancy attenuates hippocampal glucocorticoid receptor gene expression and elevates blood pressure in the adult offspring in the rat. Neuroendocrinology. 1996;64:412–418. doi: 10.1159/000127146.
    1. Harris A., Seckl J. Glucocorticoids, prenatal stress and the programming of disease. Horm. Behav. 2011;59:279–289. doi: 10.1016/j.yhbeh.2010.06.007.
    1. Champagne F.A., Francis D.D., Mar A., Meaney M.J. Variations in maternal care in the rat as a mediating influence for the effects of environment on development. Physiol. Behav. 2003;79:359–371. doi: 10.1016/S0031-9384(03)00149-5.
    1. Caldji C., Tannenbaum B., Sharma S., Francis D., Plotsky P.M., Meaney M.J. Maternal care during infancy regulates the development of neural systems mediating the expression of fearfulness in the rat. Proc. Natl. Acad. Sci. USA. 1998;95:5335–5340. doi: 10.1073/pnas.95.9.5335.
    1. Francis D., Diorio J., Liu D., Meaney M.J. Nongenomic transmission across generations of maternal behavior and stress responses in the rat. Science. 1999;286:1155–1158. doi: 10.1126/science.286.5442.1155.
    1. Liu D., Diorio J., Tannenbaum B., Caldji C., Francis D., Freedman A., Sharma S., Pearson D., Plotsky P.M., Meaney M.J. Maternal care, hippocampal glucocorticoid receptors, and hypothalamic-pituitary-adrenal responses to stress. Science. 1997;277:1659–1662. doi: 10.1126/science.277.5332.1659.
    1. Menard J.L., Champagne D.L., Meaney M.J. Variations of maternal care differentially influence ‘fear’ reactivity and regional patterns of cfos immunoreactivity in response to the shock-probe burying test. Neuroscience. 2004;129:297–308. doi: 10.1016/j.neuroscience.2004.08.009.
    1. van Hasselt F.N., Cornelisse S., Zhang T.Y., Meaney M.J., Velzing E.H., Krugers H.J., Joels M. Adult hippocampal glucocorticoid receptor expression and dentate synaptic plasticity correlate with maternal care received by individuals early in life. Hippocampus. 2012;22:255–266. doi: 10.1002/hipo.20892.
    1. Weaver I.C., Cervoni N., Champagne F.A., D’Alessio A.C., Sharma S., Seckl J.R., Dymov S., Szyf M., Meaney M.J. Epigenetic programming by maternal behavior. Nat. Neurosci. 2004;7:847–854. doi: 10.1038/nn1276.
    1. Zhang T.Y., Bagot R., Parent C., Nesbitt C., Bredy T.W., Caldji C., Fish E., Anisman H., Szyf M., Meaney M.J. Maternal programming of defensive responses through sustained effects on gene expression. Biol. Psychol. 2006;73:72–89. doi: 10.1016/j.biopsycho.2006.01.009.
    1. Liu D., Diorio J., Day J.C., Francis D.D., Meaney M.J. Maternal care, hippocampal synaptogenesis and cognitive development in rats. Nat. Neurosci. 2000;3:799–806.
    1. Pena C.J., Neugut Y.D., Calarco C.A., Champagne F.A. Effects of maternal care on the development of midbrain dopamine pathways and reward-directed behavior in female offspring. Eur. J. Neurosci. 2014;39:946–956. doi: 10.1111/ejn.12479.
    1. Starr-Phillips E.J., Beery A.K. Natural variation in maternal care shapes adult social behavior in rats. Dev. Psychobiol. 2014;56:1017–1026. doi: 10.1002/dev.21182.
    1. Essex M.J., Klein M.H., Cho E., Kalin N.H. Maternal stress beginning in infancy may sensitize children to later stress exposure: Effects on cortisol and behavior. Biol. Psychiatry. 2002;52:776–784. doi: 10.1016/S0006-3223(02)01553-6.
    1. Barry T.J., Murray L., Fearon R.M., Moutsiana C., Cooper P., Goodyer I.M., Herbert J., Halligan S.L. Maternal postnatal depression predicts altered offspring biological stress reactivity in adulthood. Psychoneuroendocrinology. 2015;52:251–260. doi: 10.1016/j.psyneuen.2014.12.003.
    1. McCauley J., Kern D.E., Kolodner K., Dill L., Schroeder A.F., DeChant H.K., Ryden J., Derogatis L.R., Bass E.B. Clinical characteristics of women with a history of childhood abuse: Unhealed wounds. JAMA. 1997;277:1362–1368. doi: 10.1001/jama.1997.03540410040028.
    1. Yaari A., Eisenberg E., Adler R., Birkhan J. Chronic pain in holocaust survivors. J. Pain Symptom Manag. 1999;17:181–187. doi: 10.1016/S0885-3924(98)00122-5.
    1. Young Casey C., Greenberg M.A., Nicassio P.M., Harpin R.E., Hubbard D. Transition from acute to chronic pain and disability: A model including cognitive, affective, and trauma factors. Pain. 2008;134:69–79. doi: 10.1016/j.pain.2007.03.032.
    1. Young E.A., Haskett R.F., Murphy-Weinberg V., Watson S.J., Akil H. Loss of glucocorticoid fast feedback in depression. Arch. Gen. Psychiatry. 1991;48:693–699. doi: 10.1001/archpsyc.1991.01810320017003.
    1. Yehuda R. Biology of posttraumatic stress disorder. J Clin Psychiatry. 2000;61(Suppl. 7):14–21.
    1. Muhtz C., Rodriguez-Raecke R., Hinkelmann K., Moeller-Bertram T., Kiefer F., Wiedemann K., May A., Otte C. Cortisol response to experimental pain in patients with chronic low back pain and patients with major depression. Pain Med. 2013;14:498–503. doi: 10.1111/j.1526-4637.2012.01514.x.
    1. Grunau R.E., Cepeda I.L., Chau C.M., Brummelte S., Weinberg J., Lavoie P.M., Ladd M., Hirschfeld A.F., Russell E., Koren G., et al. Neonatal pain-related stress and nfkbia genotype are associated with altered cortisol levels in preterm boys at school age. PLoS ONE. 2013;8:e73926. doi: 10.1371/journal.pone.0073926.
    1. Brummelte S., Chau C.M., Cepeda I.L., Degenhardt A., Weinberg J., Synnes A.R., Grunau R.E. Cortisol levels in former preterm children at school age are predicted by neonatal procedural pain-related stress. Psychoneuroendocrinology. 2015;51:151–163. doi: 10.1016/j.psyneuen.2014.09.018.
    1. McCormack K., Sanchez M.M., Bardi M., Maestripieri D. Maternal care patterns and behavioral development of rhesus macaque abused infants in the first 6 months of life. Dev. Psychobiol. 2006;48:537–550. doi: 10.1002/dev.20157.
    1. Kaufman J., Birmaher B., Perel J., Dahl R.E., Moreci P., Nelson B., Wells W., Ryan N.D. The corticotropin-releasing hormone challenge in depressed abused, depressed nonabused, and normal control children. Biol. Psychiatry. 1997;42:669–679. doi: 10.1016/S0006-3223(96)00470-2.
    1. De Bellis M.D., Chrousos G.P., Dorn L.D., Burke L., Helmers K., Kling M.A., Trickett P.K., Putnam F.W. Hypothalamic-pituitary-adrenal axis dysregulation in sexually abused girls. J. Clin. Endocrinol. Metab. 1994;78:249–255.
    1. Weems C.F., Carrion V.G. The association between ptsd symptoms and salivary cortisol in youth: The role of time since the trauma. J. Trauma. Stress. 2007;20:903–907. doi: 10.1002/jts.20251.
    1. Laplante P., Diorio J., Meaney M.J. Serotonin regulates hippocampal glucocorticoid receptor expression via a 5-ht7 receptor. Brain Res. Dev. Brain Res. 2002;139:199–203. doi: 10.1016/S0165-3806(02)00550-3.
    1. Charnay Y., Leger L. Brain serotonergic circuitries. Dialogues Clin. Neurosci. 2010;12:471–487.
    1. Suzuki R., Rygh L.J., Dickenson A.H. Bad news from the brain: Descending 5-ht pathways that control spinal pain processing. Trends Pharmacol. Sci. 2004;25:613–617. doi: 10.1016/j.tips.2004.10.002.
    1. Sommer C. Is serotonin hyperalgesic or analgesic? Curr. Pain Headache Rep. 2006;10:101–106. doi: 10.1007/s11916-006-0020-4.
    1. Wolfe F., Russell I.J., Vipraio G., Ross K., Anderson J. Serotonin levels, pain threshold, and fibromyalgia symptoms in the general population. J. Rheumatol. 1997;24:555–559.
    1. Russell I.J., Vaeroy H., Javors M., Nyberg F. Cerebrospinal fluid biogenic amine metabolites in fibromyalgia/fibrositis syndrome and rheumatoid arthritis. Arthritis Rheumatol. 1992;35:550–556. doi: 10.1002/art.1780350509.
    1. Aira Z., Buesa I., Salgueiro M., Bilbao J., Aguilera L., Zimmermann M., Azkue J.J. Subtype-specific changes in 5-ht receptor-mediated modulation of c fibre-evoked spinal field potentials are triggered by peripheral nerve injury. Neuroscience. 2010;168:831–841. doi: 10.1016/j.neuroscience.2010.04.032.
    1. Nicholl B.I., Holliday K.L., Macfarlane G.J., Thomson W., Davies K.A., O’Neill T.W., Bartfai G., Boonen S., Casanueva F.F., Finn J.D., et al. Association of htr2a polymorphisms with chronic widespread pain and the extent of musculoskeletal pain: Results from two population-based cohorts. Arthritis Rheumatol. 2011;63:810–818. doi: 10.1002/art.30185.
    1. Hanley G.E., Oberlander T.F. Neurodevelopmental outcomes following prenatal exposure to serotonin reuptake inhibitor antidepressants: A "social teratogen" or moderator of developmental risk? Birth Defects Res. A Clin. Mol. Teratol. 2012;94:651–659. doi: 10.1002/bdra.23032.
    1. Heils A., Teufel A., Petri S., Stober G., Riederer P., Bengel D., Lesch K.P. Allelic variation of human serotonin transporter gene expression. J. Neurochem. 1996;66:2621–2624. doi: 10.1046/j.1471-4159.1996.66062621.x.
    1. Offenbaecher M., Bondy B., de Jonge S., Glatzeder K., Kruger M., Schoeps P., Ackenheil M. Possible association of fibromyalgia with a polymorphism in the serotonin transporter gene regulatory region. Arthritis Rheumatol. 1999;42:2482–2488. doi: 10.1002/1529-0131(199911)42:11<2482::AID-ANR27>;2-B.
    1. Cohen H., Buskila D., Neumann L., Ebstein R.P. Confirmation of an association between fibromyalgia and serotonin transporter promoter region (5- httlpr) polymorphism, and relationship to anxiety-related personality traits. Arthritis Rheumatol. 2002;46:845–847. doi: 10.1002/art.10103.
    1. Homberg J.R., Lesch K.P. Looking on the bright side of serotonin transporter gene variation. Biol. Psychiatry. 2011;69:513–519. doi: 10.1016/j.biopsych.2010.09.024.
    1. Miller R., Wankerl M., Stalder T., Kirschbaum C., Alexander N. The serotonin transporter gene-linked polymorphic region (5-httlpr) and cortisol stress reactivity: A meta-analysis. Mol. Psychiatry. 2013;18:1018–1024. doi: 10.1038/mp.2012.124.
    1. Hariri A.R., Mattay V.S., Tessitore A., Kolachana B., Fera F., Goldman D., Egan M.F., Weinberger D.R. Serotonin transporter genetic variation and the response of the human amygdala. Science. 2002;297:400–403. doi: 10.1126/science.1071829.
    1. Heinz A., Braus D.F., Smolka M.N., Wrase J., Puls I., Hermann D., Klein S., Grusser S.M., Flor H., Schumann G., et al. Amygdala-prefrontal coupling depends on a genetic variation of the serotonin transporter. Nat. Neurosci. 2005;8:20–21. doi: 10.1038/nn1366.
    1. Hariri A.R., Holmes A. Genetics of emotional regulation: The role of the serotonin transporter in neural function. Trends Cogn. Sci. 2006;10:182–191. doi: 10.1016/j.tics.2006.02.011.
    1. Canli T., Lesch K.P. Long story short: The serotonin transporter in emotion regulation and social cognition. Nat. Neurosci. 2007;10:1103–1109. doi: 10.1038/nn1964.
    1. Huang E.J., Reichardt L.F. Neurotrophins: Roles in neuronal development and function. Annu. Rev. Neurosci. 2001;24:677–736. doi: 10.1146/annurev.neuro.24.1.677.
    1. Rasmusson A.M., Shi L., Duman R. Downregulation of bdnf mrna in the hippocampal dentate gyrus after re-exposure to cues previously associated with footshock. Neuropsychopharmacology. 2002;27:133–142. doi: 10.1016/S0893-133X(02)00286-5.
    1. Govindarajan A., Rao B.S., Nair D., Trinh M., Mawjee N., Tonegawa S., Chattarji S. Transgenic brain-derived neurotrophic factor expression causes both anxiogenic and antidepressant effects. Proc. Natl. Acad. Sci. USA. 2006;103:13208–13213. doi: 10.1073/pnas.0605180103.
    1. Lakshminarasimhan H., Chattarji S. Stress leads to contrasting effects on the levels of brain derived neurotrophic factor in the hippocampus and amygdala. PLoS ONE. 2012;7:e30481. doi: 10.1371/journal.pone.0030481.
    1. Mutso A.A., Petre B., Huang L., Baliki M.N., Torbey S., Herrmann K.M., Schnitzer T.J., Apkarian A.V. Reorganization of hippocampal functional connectivity with transition to chronic back pain. J. Neurophysiol. 2014;111:1065–1076. doi: 10.1152/jn.00611.2013.
    1. Jiang Y., Oathes D., Hush J., Darnall B., Charvat M., Mackey S., Etkin A. Perturbed connectivity of the amygdala and its subregions with the central executive and default mode networks in chronic pain. Pain. 2016;157:1970–1978. doi: 10.1097/j.pain.0000000000000606.
    1. Duric V., McCarson K.E. Effects of analgesic or antidepressant drugs on pain- or stress-evoked hippocampal and spinal neurokinin-1 receptor and brain-derived neurotrophic factor gene expression in the rat. J. Pharmacol. Exp. Ther. 2006;319:1235–1243. doi: 10.1124/jpet.106.109470.
    1. Heldt S.A., Stanek L., Chhatwal J.P., Ressler K.J. Hippocampus-specific deletion of bdnf in adult mice impairs spatial memory and extinction of aversive memories. Mol. Psychiatry. 2007;12:656–670. doi: 10.1038/sj.mp.4001957.
    1. Fukuhara K., Ishikawa K., Yasuda S., Kishishita Y., Kim H.K., Kakeda T., Yamamoto M., Norii T., Ishikawa T. Intracerebroventricular 4-methylcatechol (4-mc) ameliorates chronic pain associated with depression-like behavior via induction of brain-derived neurotrophic factor (bdnf) Cell. Mol. Neurobiol. 2012;32:971–977. doi: 10.1007/s10571-011-9782-2.
    1. Egan M.F., Goldberg T.E., Kolachana B.S., Callicott J.H., Mazzanti C.M., Straub R.E., Goldman D., Weinberger D.R. Effect of comt val108/158 met genotype on frontal lobe function and risk for schizophrenia. Proc. Natl. Acad. Sci. USA. 2001;98:6917–6922. doi: 10.1073/pnas.111134598.
    1. Egan M.F., Kojima M., Callicott J.H., Goldberg T.E., Kolachana B.S., Bertolino A., Zaitsev E., Gold B., Goldman D., Dean M., et al. The bdnf val66met polymorphism affects activity-dependent secretion of bdnf and human memory and hippocampal function. Cell. 2003;112:257–269. doi: 10.1016/S0092-8674(03)00035-7.
    1. Pezawas L., Verchinski B.A., Mattay V.S., Callicott J.H., Kolachana B.S., Straub R.E., Egan M.F., Meyer-Lindenberg A., Weinberger D.R. The brain-derived neurotrophic factor val66met polymorphism and variation in human cortical morphology. J. Neurosci. 2004;24:10099–10102. doi: 10.1523/JNEUROSCI.2680-04.2004.
    1. Kennedy K.M., Rodrigue K.M., Land S.J., Raz N. Bdnf val66met polymorphism influences age differences in microstructure of the corpus callosum. Front. Hum. Neurosci. 2009;3:19. doi: 10.3389/neuro.09.019.2009.
    1. Montag C., Weber B., Fliessbach K., Elger C., Reuter M. The bdnf val66met polymorphism impacts parahippocampal and amygdala volume in healthy humans: Incremental support for a genetic risk factor for depression. Psychol. Med. 2009;39:1831–1839. doi: 10.1017/S0033291709005509.
    1. Soliman F., Glatt C.E., Bath K.G., Levita L., Jones R.M., Pattwell S.S., Jing D., Tottenham N., Amso D., Somerville L.H., et al. A genetic variant bdnf polymorphism alters extinction learning in both mouse and human. Science. 2010;327:863–866. doi: 10.1126/science.1181886.
    1. Hajek T., Kopecek M., Hoschl C. Reduced hippocampal volumes in healthy carriers of brain-derived neurotrophic factor val66met polymorphism: Meta-analysis. World J. Biol. Psychiatry. 2012;13:178–187. doi: 10.3109/15622975.2011.580005.
    1. Molendijk M.L., Bus B.A., Spinhoven P., Kaimatzoglou A., Oude Voshaar R.C., Penninx B.W., van I.M.H., Elzinga B.M. A systematic review and meta-analysis on the association between bdnf val(66)met and hippocampal volume--a genuine effect or a winners curse? Am. J. Med. Genet. B Neuropsychiatr. Genet. 2012;159B:731–740. doi: 10.1002/ajmg.b.32078.
    1. Kim S.N., Kang D.H., Yun J.Y., Lee T.Y., Jung W.H., Jang J.H., Kwon J.S. Impact of the bdnf val66met polymorphism on regional brain gray matter volumes: Relevance to the stress response. Psychiatry Investig. 2013;10:173–179. doi: 10.4306/pi.2013.10.2.173.
    1. Xu H., Qing H., Lu W., Keegan D., Richardson J.S., Chlan-Fourney J., Li X.M. Quetiapine attenuates the immobilization stress-induced decrease of brain-derived neurotrophic factor expression in rat hippocampus. Neurosci. Lett. 2002;321:65–68. doi: 10.1016/S0304-3940(02)00034-4.
    1. Chen Z.Y., Jing D., Bath K.G., Ieraci A., Khan T., Siao C.J., Herrera D.G., Toth M., Yang C., McEwen B.S., et al. Genetic variant bdnf (val66met) polymorphism alters anxiety-related behavior. Science. 2006;314:140–143. doi: 10.1126/science.1129663.
    1. Garcia L.S., Comim C.M., Valvassori S.S., Reus G.Z., Barbosa L.M., Andreazza A.C., Stertz L., Fries G.R., Gavioli E.C., Kapczinski F., et al. Acute administration of ketamine induces antidepressant-like effects in the forced swimming test and increases bdnf levels in the rat hippocampus. Prog. Neuropsychopharmacol. Biol. Psychiatry. 2008;32:140–144. doi: 10.1016/j.pnpbp.2007.07.027.
    1. Pivac N., Kozaric-Kovacic D., Grubisic-Ilic M., Nedic G., Rakos I., Nikolac M., Blazev M., Muck-Seler D. The association between brain-derived neurotrophic factor val66met variants and psychotic symptoms in posttraumatic stress disorder. World J. Biol. Psychiatry. 2012;13:306–311. doi: 10.3109/15622975.2011.582883.
    1. Gao S., Cui Y.L., Yu C.Q., Wang Q.S., Zhang Y. Tetrandrine exerts antidepressant-like effects in animal models: Role of brain-derived neurotrophic factor. Behav. Brain Res. 2013;238:79–85. doi: 10.1016/j.bbr.2012.10.015.
    1. Lee L.C., Tu C.H., Chen L.F., Shen H.D., Chao H.T., Lin M.W., Hsieh J.C. Association of brain-derived neurotrophic factor gene val66met polymorphism with primary dysmenorrhea. PLoS ONE. 2014;9:e112766. doi: 10.1371/journal.pone.0112766.
    1. Reddy S.Y., Rasmussen N.A., Fourie N.H., Berger R.S., Martino A.C., Gill J., Longchamps R., Wang X.M., Heitkemper M.M., Henderson W.A. Sleep quality, bdnf genotype and gene expression in individuals with chronic abdominal pain. BMC Med. Genom. 2014;7:61. doi: 10.1186/s12920-014-0061-1.
    1. Zhang L., Benedek D.M., Fullerton C.S., Forsten R.D., Naifeh J.A., Li X.X., Hu X.Z., Li H., Jia M., Xing G.Q., et al. Ptsd risk is associated with bdnf val66met and bdnf overexpression. Mol. Psychiatry. 2014;19:8–10. doi: 10.1038/mp.2012.180.
    1. Generaal E., Milaneschi Y., Jansen R., Elzinga B.M., Dekker J., Penninx B.W. The brain-derived neurotrophic factor pathway, life stress, and chronic multi-site musculoskeletal pain. Mol. Pain. 2016;12 doi: 10.1177/1744806916646783.
    1. Trang T., Beggs S., Salter M.W. Brain-derived neurotrophic factor from microglia: A molecular substrate for neuropathic pain. Neuron. Glia Biol. 2011;7:99–108. doi: 10.1017/S1740925X12000087.
    1. Watkins L.R., Hutchinson M.R., Ledeboer A., Wieseler-Frank J., Milligan E.D., Maier S.F. Norman cousins lecture. Glia as the “bad guys”: Implications for improving clinical pain control and the clinical utility of opioids. Brain Behav. Immun. 2007;21:131–146. doi: 10.1016/j.bbi.2006.10.011.
    1. Uceyler N., Sommer C. Cytokine-related and histological biomarkers for neuropathic pain assessment. Pain Manag. 2012;2:391–398. doi: 10.2217/pmt.12.28.
    1. Ransohoff R.M. How neuroinflammation contributes to neurodegeneration. Science. 2016;353:777–783. doi: 10.1126/science.aag2590.
    1. Pankratz S., Bittner S., Kehrel B.E., Langer H.F., Kleinschnitz C., Meuth S.G., Gobel K. The inflammatory role of platelets: Translational insights from experimental studies of autoimmune disorders. Int. J. Mol. Sci. 2016;17 doi: 10.3390/ijms17101723.
    1. Benson S., Engler H., Schedlowski M., Elsenbruch S. Experimental endotoxemia as a model to study neuroimmune mechanisms in human visceral pain. Ann. N. Y. Acad. Sci. 2012;1262:108–117. doi: 10.1111/j.1749-6632.2012.06622.x.
    1. Del Valle L., Schwartzman R.J., Alexander G. Spinal cord histopathological alterations in a patient with longstanding complex regional pain syndrome. Brain Behav. Immun. 2009;23:85–91. doi: 10.1016/j.bbi.2008.08.004.
    1. Shi Y., Gelman B.B., Lisinicchia J.G., Tang S.J. Chronic-pain-associated astrocytic reaction in the spinal cord dorsal horn of human immunodeficiency virus-infected patients. J. Neurosci. 2012;32:10833–10840. doi: 10.1523/JNEUROSCI.5628-11.2012.
    1. Brisby H., Olmarker K., Rosengren L., Cederlund C.G., Rydevik B. Markers of nerve tissue injury in the cerebrospinal fluid in patients with lumbar disc herniation and sciatica. Spine. 1999;24:742–746. doi: 10.1097/00007632-199904150-00003.
    1. Kadetoff D., Lampa J., Westman M., Andersson M., Kosek E. Evidence of central inflammation in fibromyalgia-increased cerebrospinal fluid interleukin-8 levels. J. Neuroimmunol. 2012;242:33–38. doi: 10.1016/j.jneuroim.2011.10.013.
    1. Loggia M.L., Chonde D.B., Akeju O., Arabasz G., Catana C., Edwards R.R., Hill E., Hsu S., Izquierdo-Garcia D., Ji R.R., et al. Evidence for brain glial activation in chronic pain patients. Brain. 2015;138:604–615. doi: 10.1093/brain/awu377.
    1. Fiore N.T., Austin P.J. Are the emergence of affective disturbances in neuropathic pain states contingent on supraspinal neuroinflammation? Brain Behav. Immun. 2016;56:397–411. doi: 10.1016/j.bbi.2016.04.012.
    1. Goshen I., Kreisel T., Ben-Menachem-Zidon O., Licht T., Weidenfeld J., Ben-Hur T., Yirmiya R. Brain interleukin-1 mediates chronic stress-induced depression in mice via adrenocortical activation and hippocampal neurogenesis suppression. Mol. Psychiatry. 2008;13:717–728. doi: 10.1038/sj.mp.4002055.
    1. Goshen I., Kreisel T., Ounallah-Saad H., Renbaum P., Zalzstein Y., Ben-Hur T., Levy-Lahad E., Yirmiya R. A dual role for interleukin-1 in hippocampal-dependent memory processes. Psychoneuroendocrinology. 2007;32:1106–1115. doi: 10.1016/j.psyneuen.2007.09.004.
    1. Besedovsky H.O., del Rey A. Immune-neuro-endocrine interactions: Facts and hypotheses. Endocr. Rev. 1996;17:64–102. doi: 10.1210/edrv-17-1-64.
    1. Pace T.W., Hu F., Miller A.H. Cytokine-effects on glucocorticoid receptor function: Relevance to glucocorticoid resistance and the pathophysiology and treatment of major depression. Brain Behav. Immun. 2007;21:9–19. doi: 10.1016/j.bbi.2006.08.009.
    1. Vogelzangs N., de Jonge P., Smit J.H., Bahn S., Penninx B.W. Cytokine production capacity in depression and anxiety. Transl. Psychiatry. 2016;6:e825. doi: 10.1038/tp.2016.92.
    1. Lasselin J., Kemani M.K., Kanstrup M., Olsson G.L., Axelsson J., Andreasson A., Lekander M., Wicksell R.K. Low-grade inflammation may moderate the effect of behavioral treatment for chronic pain in adults. J. Behav. Med. 2016 doi: 10.1007/s10865-016-9769-z.
    1. Beggs S., Currie G., Salter M.W., Fitzgerald M., Walker S.M. Priming of adult pain responses by neonatal pain experience: Maintenance by central neuroimmune activity. Brain. 2012;135:404–417. doi: 10.1093/brain/awr288.
    1. Mitchell R.H., Goldstein B.I. Inflammation in children and adolescents with neuropsychiatric disorders: A systematic review. J. Am. Acad. Child Adolesc. Psychiatry. 2014;53:274–296. doi: 10.1016/j.jaac.2013.11.013.
    1. Ganguly P., Brenhouse H.C. Broken or maladaptive? Altered trajectories in neuroinflammation and behavior after early life adversity. Dev. Cogn. Neurosci. 2015;11:18–30. doi: 10.1016/j.dcn.2014.07.001.
    1. Gill J., Luckenbaugh D., Charney D., Vythilingam M. Sustained elevation of serum interleukin-6 and relative insensitivity to hydrocortisone differentiates posttraumatic stress disorder with and without depression. Biol. Psychiatry. 2010;68:999–1006. doi: 10.1016/j.biopsych.2010.07.033.
    1. Lerman I., Davis B.A., Bertram T.M., Proudfoot J., Hauger R.L., Coe C.L., Patel P.M., Baker D.G. Posttraumatic stress disorder influences the nociceptive and intrathecal cytokine response to a painful stimulus in combat veterans. Psychoneuroendocrinology. 2016;73:99–108. doi: 10.1016/j.psyneuen.2016.07.202.
    1. Kopf M., Bachmann M.F., Marsland B.J. Averting inflammation by targeting the cytokine environment. Nat. Rev. Drug Discov. 2010;9:703–718. doi: 10.1038/nrd2805.
    1. Apkarian A.V., Bushnell M.C., Treede R.D., Zubieta J.K. Human brain mechanisms of pain perception and regulation in health and disease. Eur. J. Pain. 2005;9:463–484. doi: 10.1016/j.ejpain.2004.11.001.
    1. Bushnell M.C., Ceko M., Low L.A. Cognitive and emotional control of pain and its disruption in chronic pain. Nat. Rev. Neurosci. 2013;14:502–511. doi: 10.1038/nrn3516.
    1. Duerden E.G., Albanese M.C. Localization of pain-related brain activation: A meta-analysis of neuroimaging data. Hum. Brain Mapp. 2013;34:109–149. doi: 10.1002/hbm.21416.
    1. Iadarola M.J., Coghill R.C. Imaging of pain: Recent developments. Curr. Opin. Anaesthesiol. 1999;12:583–589. doi: 10.1097/00001503-199910000-00016.
    1. Willis W.D., Westlund K.N. Neuroanatomy of the pain system and of the pathways that modulate pain. J. Clin. Neurophysiol. 1997;14:2–31. doi: 10.1097/00004691-199701000-00002.
    1. Atlas L.Y., Lindquist M.A., Bolger N., Wager T.D. Brain mediators of the effects of noxious heat on pain. Pain. 2014;155:1632–1648. doi: 10.1016/j.pain.2014.05.015.
    1. Coghill R.C., Sang C.N., Maisog J.M., Iadarola M.J. Pain intensity processing within the human brain: A bilateral, distributed mechanism. J. Neurophysiol. 1999;82:1934–1943.
    1. Wager T.D., Atlas L.Y., Lindquist M.A., Roy M., Woo C.W., Kross E. An fmri-based neurologic signature of physical pain. N. Engl. J. Med. 2013;368:1388–1397. doi: 10.1056/NEJMoa1204471.
    1. Hubbard C.S., Khan S.A., Xu S., Cha M., Masri R., Seminowicz D.A. Behavioral, metabolic and functional brain changes in a rat model of chronic neuropathic pain: A longitudinal mri study. Neuroimage. 2015;107:333–344. doi: 10.1016/j.neuroimage.2014.12.024.
    1. Jensen K.B., Regenbogen C., Ohse M.C., Frasnelli J., Freiherr J., Lundstrom J.N. Brain activations during pain: A neuroimaging meta-analysis of patients with pain and healthy controls. Pain. 2016;157:1279–1286. doi: 10.1097/j.pain.0000000000000517.
    1. 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. doi: 10.1038/nn.3153.
    1. Hubbard C.S., Becerra L., Heinz N., Ludwick A., Rasooly T., Wu R., Johnson A., Schechter N.L., Borsook D., Nurko S. Abdominal pain, the adolescent and altered brain structure and function. PLoS ONE. 2016;11:e0156545. doi: 10.1371/journal.pone.0156545.
    1. Simons L.E., Pielech M., Erpelding N., Linnman C., Moulton E., Sava S., Lebel A., Serrano P., Sethna N., Berde C., et al. The responsive amygdala: Treatment-induced alterations in functional connectivity in pediatric complex regional pain syndrome. Pain. 2014;155:1727–1742. doi: 10.1016/j.pain.2014.05.023.
    1. Simons L.E., Erpelding N., Hernandez J., Serrano P., Zhang K., Lebel A., Sethna N., Berde C., Prabhu S., Becerra L., et al. Fear and reward circuit alterations in pediatric crps. Front. Hum. Neurosci. 2016;9:1–13. doi: 10.3389/fnhum.2015.00703.
    1. Lebel A., Becerra L., Wallin D., Moulton E.A., Morris S., Pendse G., Jasciewicz J., Stein M., Aiello-Lammens M., Grant E., et al. Fmri reveals distinct cns processing during symptomatic and recovered complex regional pain syndrome in children. Brain. 2008;131:1854–1879. doi: 10.1093/brain/awn123.
    1. McEwen B.S., Kalia M. The role of corticosteroids and stress in chronic pain conditions. Metabolism. 2010;59(Suppl. 1):S9–S15. doi: 10.1016/j.metabol.2010.07.012.
    1. Karatsoreos I.N., McEwen B.S. Psychobiological allostasis: Resistance, resilience and vulnerability. Trends Cogn. Sci. 2011;15:576–584. doi: 10.1016/j.tics.2011.10.005.
    1. Becerra L., Sava S., Simons L.E., Drosos A.M., Sethna N., Berde C., Lebel A.A., Borsook D. Intrinsic brain networks normalize with treatment in pediatric complex regional pain syndrome. Neuroimage Clin. 2014;6:347–369. doi: 10.1016/j.nicl.2014.07.012.
    1. Coutinho J.F., Fernandesl S.V., Soares J.M., Maia L., Goncalves O.F., Sampaio A. Default mode network dissociation in depressive and anxiety states. Brain Imaging Behav. 2016;10:147–157. doi: 10.1007/s11682-015-9375-7.
    1. Geng H., Li X., Chen J., Li X., Gu R. Decreased intra- and inter-salience network functional connectivity is related to trait anxiety in adolescents. Front. Behav. Neurosci. 2015;9:350. doi: 10.3389/fnbeh.2015.00350.
    1. Lei D., Li L., Li L., Suo X., Huang X., Lui S., Li J., Bi F., Kemp G.J., Gong Q. Microstructural abnormalities in children with post-traumatic stress disorder: A diffusion tensor imaging study at 3.0t. Sci. Rep. 2015;5:8933. doi: 10.1038/srep08933.
    1. Pannekoek J.N., van der Werff S.J., Meens P.H., van den Bulk B.G., Jolles D.D., Veer I.M., van Lang N.D., Rombouts S.A., van der Wee N.J., Vermeiren R.R. Aberrant resting-state functional connectivity in limbic and salience networks in treatment--naive clinically depressed adolescents. J. Child Psychol. Psychiatry. 2014;55:1317–1327. doi: 10.1111/jcpp.12266.
    1. Schanberg L.E., Anthony K.K., Gil K.M., Lefebvre J.C., Kredich D.W., Macharoni L.M. Family pain history predicts child health status in children with chronic rheumatic disease. Pediatrics. 2001;108:E47. doi: 10.1542/peds.108.3.e47.
    1. Garber J., Zeman J., Walker L.S. Recurrent abdominal pain in children: Psychiatric diagnoses and parental psychopathology. J. Am. Acad. Child Adolesc. Psychiatry. 1990;29:648–656. doi: 10.1097/00004583-199007000-00021.
    1. Hoftun G.B., Romundstad P.R., Rygg M. Factors associated with adolescent chronic non-specific pain, chronic multisite pain, and chronic pain with high disability: The young-hunt study 2008. J. Pain. 2012 doi: 10.1016/j.jpain.2012.06.001.
    1. Morgan J.E., Hammen C., Lee S.S. Parental serotonin transporter polymorphism (5-httlpr) moderates associations of stress and child behavior with parenting behavior. J. Clin. Child Adolesc. Psychol. 2016:1–12. doi: 10.1080/15374416.2016.1152550.
    1. Roth T.L., Lubin F.D., Funk A.J., Sweatt J.D. Lasting epigenetic influence of early-life adversity on the bdnf gene. Biol. Psychiatry. 2009;65:760–769. doi: 10.1016/j.biopsych.2008.11.028.
    1. van der Doelen R.H., Arnoldussen I.A., Ghareh H., van Och L., Homberg J.R., Kozicz T. Early life adversity and serotonin transporter gene variation interact to affect DNA methylation of the corticotropin-releasing factor gene promoter region in the adult rat brain. Dev. Psychopathol. 2015;27:123–135. doi: 10.1017/S0954579414001345.
    1. Walker L.S., Greene J.W. Children with recurrent abdominal pain and their parents: More somatic complaints, anxiety, and depression than other patient families? J. Pediatr. Psychol. 1989;14:231–243. doi: 10.1093/jpepsy/14.2.231.
    1. Campo J.V., Bridge J., Lucas A., Savorelli S., Walker L., Di Lorenzo C., Iyengar S., Brent D.A. Physical and emotional health of mothers of youth with functional abdominal pain. Arch. Pediatr. Adolesc. Med. 2007;161:131–137. doi: 10.1001/archpedi.161.2.131.
    1. Williamson G.M., Walters A.S., Shaffer D.R. Caregiver models of self and others, coping, and depression: Predictors of depression in children with chronic pain. Health Psychol. 2002;21:405–410. doi: 10.1037/0278-6133.21.4.405.
    1. Wolff N., Darlington A.S., Hunfeld J., Verhulst F., Jaddoe V., Hofman A., Passchier J., Tiemeier H. Determinants of somatic complaints in 18-month-old children: The generation r study. J. Pediatr. Psychol. 2010;35:306–316. doi: 10.1093/jpepsy/jsp058.
    1. Higgins K.S., Birnie K.A., Chambers C.T., Wilson A.C., Caes L., Clark A.J., Lynch M., Stinson J., Campbell-Yeo M. Offspring of parents with chronic pain: A systematic review and meta-analysis of pain, health, psychological, and family outcomes. Pain. 2015;156:2256–2266. doi: 10.1097/j.pain.0000000000000293.
    1. Levy R.L., Whitehead W.E., Von Korff M.R., Feld A.D. Intergenerational transmission of gastrointestinal illness behavior. Am. J. Gastroenterol. 2000;95:451–456. doi: 10.1111/j.1572-0241.2000.01766.x.
    1. van Tilburg M.A., Levy R.L., Walker L.S., Von Korff M., Feld L.D., Garner M., Feld A.D., Whitehead W.E. Psychosocial mechanisms for the transmission of somatic symptoms from parents to children. World J. Gastroenterol. 2015;21:5532–5541. doi: 10.3748/wjg.v21.i18.5532.
    1. Stone A.L., Wilson A.C. Transmission of risk from parents with chronic pain to offspring: An integrative conceptual model. Pain. 2016 doi: 10.1097/j.pain.0000000000000637.
    1. Palermo T.M., Law E.F., Fales J., Bromberg M.H., Jessen-Fiddick T., Tai G. Internet-delivered cognitive-behavioral treatment for adolescents with chronic pain and their parents: A randomized controlled multicenter trial. Pain. 2016;157:174–185. doi: 10.1097/j.pain.0000000000000348.
    1. Palermo T.M., Valrie C.R., Karlson C.W. Family and parent influences on pediatric chronic pain: A developmental perspective. Am. Psychol. 2014;69:142–152. doi: 10.1037/a0035216.
    1. Fisher E., Law E., Palermo T.M., Eccleston C. Psychological therapies (remotely delivered) for the management of chronic and recurrent pain in children and adolescents. Cochrane Database Syst. Rev. 2014;2014
    1. Cunningham N.R., Jagpal A., Tran S.T., Kashikar-Zuck S., Goldschneider K.R., Coghill R.C., Lynch-Jordan A.M. Anxiety adversely impacts response to cognitive behavioral therapy in children with chronic pain. J. Pediatr. 2016;171:227–233. doi: 10.1016/j.jpeds.2016.01.018.
    1. Benore E., D'Auria A., Banez G.A., Worley S., Tang A. The influence of anxiety reduction on clinical response to pediatric chronic pain rehabilitation. Clin. J. Pain. 2015;31:375–383. doi: 10.1097/AJP.0000000000000127.
    1. Sullivan A., Goodison-Farnsworth E., Jaaniste T. Posttraumatic stress disorder in children with chronic pain. Pediatr. Pain Lett. 2015;17:35–39.
    1. Nelson S.M., Cunningham N.R., Kashikar-Zuck S. A conceptual framework for understanding the role of adverse childhood experiences in pediatric chronic pain. Clin. J. Pain. 2016 doi: 10.1097/AJP.0000000000000397.
    1. Bosco M.A., Gallinati J.L., Clark M.E. Conceptualizing and treating comorbid chronic pain and ptsd. Pain Res. Treat. 2013;2013:174728. doi: 10.1155/2013/174728.
    1. Plagge J.M., Lu M.W., Lovejoy T.I., Karl A.I., Dobscha S.K. Treatment of comorbid pain and ptsd in returning veterans: A collaborative approach utilizing behavioral activation. Pain Med. 2013;14:1164–1172. doi: 10.1111/pme.12155.
    1. Otis J.D., Keane T.M., Kerns R.D., Monson C., Scioli E. The development of an integrated treatment for veterans with comorbid chronic pain and posttraumatic stress disorder. Pain Med. 2009;10:1300–1311. doi: 10.1111/j.1526-4637.2009.00715.x.
    1. Allen L.B., Tsao J.C.I., Seidman L.C., Ehrenreich-May J., Zeltzer L.K. A unified, transdiagnositc treatment for adolescents with chronic pain and comorbid anxiety and depression. Cogn. Behav. Pract. 2012;19:56–67. doi: 10.1016/j.cbpra.2011.04.007.
    1. Umezaki Y., Badran B.W., DeVries W.H., Moss J., Gonzales T., George M.S. The efficacy of daily prefrontal repetitive transcranial magnetic stimulation (rtms) for burning mouth syndrome (bms): A randomized controlled single-blind study. Brain Stimul. 2016;9:234–242. doi: 10.1016/j.brs.2015.10.005.
    1. Picarelli H., Teixeira M.J., de Andrade D.C., Myczkowski M.L., Luvisotto T.B., Yeng L.T., Fonoff E.T., Pridmore S., Marcolin M.A. Repetitive transcranial magnetic stimulation is efficacious as an add-on to pharmacological therapy in complex regional pain syndrome (crps) type i. J. Pain. 2010;11:1203–1210. doi: 10.1016/j.jpain.2010.02.006.
    1. Mendonca M.E., Simis M., Grecco L.C., Battistella L.R., Baptista A.F., Fregni F. Transcranial direct current stimulation combined with aerobic exercise to optimize analgesic responses in fibromyalgia: A randomized placebo-controlled clinical trial. Front. Hum. Neurosci. 2016;10:68. doi: 10.3389/fnhum.2016.00068.
    1. Short E.B., Borckardt J.J., Anderson B.S., Frohman H., Beam W., Reeves S.T., George M.S. Ten sessions of adjunctive left prefrontal rtms significantly reduces fibromyalgia pain: A randomized, controlled pilot study. Pain. 2011;152:2477–2484. doi: 10.1016/j.pain.2011.05.033.
    1. Lefaucheur J.P., Ayache S.S., Sorel M., Farhat W.H., Zouari H.G., Ciampi de Andrade D., Ahdab R., Menard-Lefaucheur I., Brugieres P., Goujon C. Analgesic effects of repetitive transcranial magnetic stimulation of the motor cortex in neuropathic pain: Influence of theta burst stimulation priming. Eur. J. Pain. 2012;16:1403–1413. doi: 10.1002/j.1532-2149.2012.00150.x.
    1. Fregni F., Boggio P.S., Lima M.C., Ferreira M.J., Wagner T., Rigonatti S.P., Castro A.W., Souza D.R., Riberto M., Freedman S.D., et al. A sham-controlled, phase ii trial of transcranial direct current stimulation for the treatment of central pain in traumatic spinal cord injury. Pain. 2006;122:197–209. doi: 10.1016/j.pain.2006.02.023.
    1. Defrin R., Grunhaus L., Zamir D., Zeilig G. The effect of a series of repetitive transcranial magnetic stimulations of the motor cortex on central pain after spinal cord injury. Arch. Phys. Med. Rehabil. 2007;88:1574–1580. doi: 10.1016/j.apmr.2007.07.025.
    1. Perera T., George M.S., Grammer G., Janicak P.G., Pascual-Leone A., Wirecki T.S. The clinical tms society consensus review and treatment recommendations for tms therapy for major depressive disorder. Brain Stimul. 2016;9:336–346. doi: 10.1016/j.brs.2016.03.010.
    1. Canadian Agency for Drugs and Technologies in Health . Transcranial Magnetic Stimulation for the Treatment of Adults with Ptsd, Gad, or Depression: A Review of Clinical Effectiveness and Guidelines. Canadian Agency for Drugs and Technologies in Health; Ottawa, ON, Canada: 2014. Cadth rapid response reports.
    1. Paes F., Machado S., Arias-Carrion O., Velasques B., Teixeira S., Budde H., Cagy M., Piedade R., Ribeiro P., Huston J.P., et al. The value of repetitive transcranial magnetic stimulation (rtms) for the treatment of anxiety disorders: An integrative review. CNS Neurol. Disord. Drug Targets. 2011;10:610–620. doi: 10.2174/187152711796234943.
    1. Naro A., Milardi D., Russo M., Terranova C., Rizzo V., Cacciola A., Marino S., Calabro R.S., Quartarone A. Non-invasive brain stimulation, a tool to revert maladaptive plasticity in neuropathic pain. Front. Hum. Neurosci. 2016;10:376. doi: 10.3389/fnhum.2016.00376.
    1. DosSantos M.F., Ferreira N., Toback R.L., Carvalho A.C., DaSilva A.F. Potential mechanisms supporting the value of motor cortex stimulation to treat chronic pain syndromes. Front. Neurosci. 2016;10 doi: 10.3389/fnins.2016.00018.
    1. Chrousos G.P. The hypothalamic-pituitary-adrenal axis and immune-mediated inflammation. N. Engl. J. Med. 1995;332:1351–1362.
    1. Elenkov I.J., Webster E.L., Torpy D.J., Chrousos G.P. Stress, corticotropin-releasing hormone, glucocorticoids, and the immune/inflammatory response: Acute and chronic effects. Ann. N. Y. Acad. Sci. 1999;876:1–11; discussion 11-13. doi: 10.1111/j.1749-6632.1999.tb07618.x.
    1. Meyer J.S. Early adrenalectomy stimulates subsequent growth and development of the rat brain. Exp. Neurol. 1983;82:432–446. doi: 10.1016/0014-4886(83)90415-6.
    1. Meaney M.J., Diorio J., Francis D., Widdowson J., LaPlante P., Caldji C., Sharma S., Seckl J.R., Plotsky P.M. Early environmental regulation of forebrain glucocorticoid receptor gene expression: Implications for adrenocortical responses to stress. Dev. Neurosci. 1996;18:49–72. doi: 10.1159/000111395.
    1. Korte S.M. Corticosteroids in relation to fear, anxiety and psychopathology. Neurosci. Biobehav. Rev. 2001;25:117–142. doi: 10.1016/S0149-7634(01)00002-1.
    1. Knook L.M., Lijmer J.G., Konijnenberg A.Y., Taminiau B., van Engeland H. The course of chronic pain with and without psychiatric disorders: A 6-year follow-up study from childhood to adolescence and young adulthood. J. Clin. Psychiatry. 2012;73:e134–e139. doi: 10.4088/JCP.10m06751.
    1. Mulak A., Tache Y., Larauche M. Sex hormones in the modulation of irritable bowel syndrome. World J. Gastroenterol. 2014;20:2433–2448. doi: 10.3748/wjg.v20.i10.2433.
    1. Karshikoff B., Lekander M., Soop A., Lindstedt F., Ingvar M., Kosek E., Olgart Hoglund C., Axelsson J. Modality and sex differences in pain sensitivity during human endotoxemia. Brain Behav. Immun. 2015;46:35–43. doi: 10.1016/j.bbi.2014.11.014.
    1. Aloisi A.M., Bachiocco V., Costantino A., Stefani R., Ceccarelli I., Bertaccini A., Meriggiola M.C. Cross-sex hormone administration changes pain in transsexual women and men. Pain. 2007;132(Suppl. 1):S60–S67. doi: 10.1016/j.pain.2007.02.006.

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