Advertisement

Neurobiological Phenotypes of Familial Chronic Pain in Adolescence: A Pilot fMRI Study

      Highlights

      • Emotional processing brain activity is altered in FH + Pain youth.
      • Emotional context affects inhibitory control brain response in FH + Pain youth.
      • Neural markers of chronic pain risk may be present in the absence of pain symptoms.

      Abstract

      Parental history of chronic pain has been associated with self-reported pain in adolescent offspring. This suggests that there may be neurobiological mechanisms associated with pain heritability. Because emotional circuitry is an important component of pain processing and may also influence cognition, we used functional magnetic resonance imaging to examine affective processing and cognitive control using an Emotional Go/NoGo task in youth with (FH + Pain, n = 8) and without (FH − Pain, n = 8) a parental history of chronic pain (mean age = 14.17 ± .34 years). FH + Pain youth had widespread reductions in brain activity within limbic and visual processing regions during processing of positively valenced emotional stimuli, as well as reduced frontoparietal response while processing negatively valenced emotional stimuli compared with their peers. In addition, during inhibition within a positive emotional context, FH + Pain youth had reduced cognitive control and salience-related brain activity. On the other hand, default mode–related brain response was increased during inhibitory control within a negative emotional context in these adolescents compared with their peers (P/α < .05). The current findings indicate differences in both emotional processing and cognitive control brain response in FH + Pain compared with FH − Pain youth, suggesting that both affective and executive functioning pathways may be important markers related to the intergenerational transmission of pain.

      Perspective

      This is the first study to examine neurobiological markers of pain risk in adolescents with a family history of chronic pain. These findings may aid in the identification of neural phenotypes related to vulnerability for the onset of pain in at-risk youth.

      Key words

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

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      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

        • Anttila P.
        • Metsahonkala L.
        • Helenius H.
        • Sillanpaa M.
        Predisposing and provoking factors in childhood headache.
        Headache. 2000; 40: 351-356
        • Bair M.J.
        • Poleshuck E.L.
        • Wu J.
        • Krebs E.K.
        • Damush T.M.
        • Tu W.
        • Kroenke K.
        Anxiety but not social stressors predict 12-month depression and pain severity.
        Clin J Pain. 2013; 29: 95-101
        • 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.
        • Chialvo D.R.
        Beyond feeling: chronic pain hurts the brain, disrupting the default-mode network dynamics.
        J Neurosci. 2008; 28: 1398-1403
        • Carskadon M.A.
        • Acebo C.
        A self-administered rating scale for pubertal development.
        J Adolesc Health. 1993; 14: 190-195
        • Cifre I.
        • Sitges C.
        • Fraiman D.
        • Munoz M.A.
        • Balenzuela P.
        • Gonzalez-Roldan A.
        • Martinez-Jauand M.
        • Birbaumer N.
        • Chialvo D.R.
        • Montoya P.
        Disrupted functional connectivity of the pain network in fibromyalgia.
        Psychosom Med. 2012; 74: 55-62
        • Cohen M.S.
        Parametric analysis of fMRI data using linear systems methods.
        Neuroimage. 1997; 6: 93-103
        • IBM Corp.
        IBM SPSS Statistics for Windows. Version 20.0.
        IBM Corp., Armonk, NY2011
        • Cox R.W.
        AFNI: software for analysis and visualization of functional magnetic resonance neuroimages.
        Comput Biomed Res. 1996; 29: 162-173
        • Cox R.W.
        • Jesmanowicz A.
        Real-time 3D image registration for functional MRI.
        Magn Reson Med. 1999; 42: 1014-1018
        • Cservenka A.
        • Fair D.A.
        • Nagel B.J.
        Emotional processing and brain activity in youth at high risk for alcoholism.
        Alcohol Clin Exp Res. 2014; 38: 1912-1923
        • Currie C.
        • Samdal O.
        • Boyce W.
        • Smith R.
        Health Behaviour in School-Aged Children: A WHO Cross-National Study (HBSC): Research Protocol for the 2001/2002 Survey, Child and Adolescent Research Unit.
        University of Edinburgh, Edinburgh2001
        • Dahl R.E.
        Affect regulation, brain development, and behavioral/emotional health in adolescence.
        CNS Spectr. 2001; 6: 60-72
        • Denk F.
        • McMahon S.B.
        • Tracey I.
        Pain vulnerability: a neurobiological perspective.
        Nat Neurosci. 2014; 17: 192-200
        • Eck J.
        • Richter M.
        • Straube T.
        • Miltner W.H.
        • Weiss T.
        Affective brain regions are activated during the processing of pain-related words in migraine patients.
        Pain. 2011; 152: 1104-1113
      1. Ellis LK, Rothbart MK: Revision of the Early Adolescent Temperament Questionnaire. In: Poster presented at the Biennial Meeting of the Society for Research in Child Development. Minneapolis, Minnesota, 2001

        • Erpelding N.
        • Sava S.
        • Simons L.E.
        • Lebel A.
        • Serrano P.
        • Becerra L.
        • Borsook D.
        Habenula functional resting-state connectivity in pediatric CRPS.
        J Neurophysiol. 2014; 111: 239-247
        • Fearon P.
        • Hotopf M.
        Relation between headache in childhood and physical and psychiatric symptoms in adulthood: national birth cohort study.
        BMJ. 2001; 322: 1145
        • Fischl B.
        FreeSurfer.
        Neuroimage. 2012; 62: 774-781
        • Forman S.D.
        • Cohen J.D.
        • Fitzgerald M.
        • Eddy W.F.
        • Mintun M.A.
        • Noll D.C.
        Improved assessment of significant activation in functional magnetic resonance imaging (fMRI): use of a cluster-size threshold.
        Magn Reson Med. 1995; 33: 636-647
        • Gatchel R.J.
        • Okifuji A.
        Evidence-based scientific data documenting the treatment and cost-effectiveness of comprehensive pain programs for chronic nonmalignant pain.
        J Pain. 2006; 7: 779-793
        • Glass J.M.
        • Williams D.A.
        • Fernandez-Sanchez M.L.
        • Kairys A.
        • Barjola P.
        • Heitzeg M.M.
        • Clauw D.J.
        • Schmidt-Wilcke T.
        Executive function in chronic pain patients and healthy controls: different cortical activation during response inhibition in fibromyalgia.
        J Pain. 2011; 12: 1219-1229
        • Gogtay N.
        • Giedd J.N.
        • Lusk L.
        • Hayashi K.M.
        • Greenstein D.
        • Vaituzis A.C.
        • Nugent 3rd, T.F.
        • Herman D.H.
        • Clasen L.S.
        • Toga A.W.
        • Rapoport J.L.
        • Thompson P.M.
        Dynamic mapping of human cortical development during childhood through early adulthood.
        Proc Natl Acad Sci U S A. 2004; 101: 8174-8179
        • Gureje O.
        • Von Korff M.
        • Simon G.E.
        • Gater R.
        Persistent pain and well-being: a World Health Organization Study in Primary Care.
        JAMA. 1998; 280: 147-151
        • Hare T.A.
        • Tottenham N.
        • Galvan A.
        • Voss H.U.
        • Glover G.H.
        • Casey B.J.
        Biological substrates of emotional reactivity and regulation in adolescence during an emotional go-nogo task.
        Biol Psychiatry. 2008; 63: 927-934
        • Hocking L.J.
        • Morris A.D.
        • Dominiczak A.F.
        • Porteous D.J.
        • Smith B.H.
        Heritability of chronic pain in 2195 extended families.
        Eur J Pain. 2012; 16: 1053-1063
        • Hollingshead A.B.
        Two Factor Index of Social Position.
        Privately printed, New Haven, CT1957
        • Ichesco E.
        • Quintero A.
        • Clauw D.J.
        • Peltier S.
        • Sundgren P.M.
        • Gerstner G.E.
        • Schmidt-Wilcke T.
        Altered functional connectivity between the insula and the cingulate cortex in patients with temporomandibular disorder: a pilot study.
        Headache. 2012; 52: 441-454
        • Ichesco E.
        • Schmidt-Wilcke T.
        • Bhavsar R.
        • Clauw D.J.
        • Peltier S.J.
        • Kim J.
        • Napadow V.
        • Hampson J.P.
        • Kairys A.E.
        • Williams D.A.
        • Harris R.E.
        Altered resting state connectivity of the insular cortex in individuals with fibromyalgia.
        J Pain. 2014; 15: 815-826.e1
        • Johannes C.B.
        • Le T.K.
        • Zhou X.
        • Johnston J.A.
        • Dworkin R.H.
        The prevalence of chronic pain in United States adults: results of an Internet-based survey.
        J Pain. 2010; 11: 1230-1239
        • Junqueira D.R.
        • Ferreira M.L.
        • Refshauge K.
        • Maher C.G.
        • Hopper J.L.
        • Hancock M.
        • Carvalho M.G.
        • Ferreira P.H.
        Heritability and lifestyle factors in chronic low back pain: results of the Australian Twin Low Back Pain Study (the AUTBACK study).
        Eur J Pain. 2014; 18: 1410-1418
        • Kashikar-Zuck S.
        • Goldschneider K.R.
        • Powers S.W.
        • Vaught M.H.
        • Hershey A.D.
        Depression and functional disability in chronic pediatric pain.
        Clin J Pain. 2001; 17: 341-349
        • Kovacs M.
        The Children's Depression Inventory (CDI).
        Psychopharmacol Bull. 1985; 21: 995-998
        • Kucyi A.
        • Moayedi M.
        • Weissman-Fogel I.
        • Goldberg M.B.
        • Freeman B.V.
        • Tenenbaum H.C.
        • Davis K.D.
        Enhanced medial prefrontal-default mode network functional connectivity in chronic pain and its association with pain rumination.
        J Neurosci. 2014; 34: 3969-3975
        • Laurell K.
        • Larsson B.
        • Eeg-Olofsson O.
        Headache in schoolchildren: association with other pain, family history and psychosocial factors.
        Pain. 2005; 119: 150-158
        • Lebel A.
        • Becerra L.
        • Wallin D.
        • Moulton E.A.
        • Morris S.
        • Pendse G.
        • Jasciewicz J.
        • Stein M.
        • Aiello-Lammens M.
        • Grant E.
        • Berde C.
        • Borsook D.
        fMRI reveals distinct CNS processing during symptomatic and recovered complex regional pain syndrome in children.
        Brain. 2008; 131: 1854-1879
        • Manning J.S.
        • Jackson W.C.
        Depression, pain, and comorbid medical conditions.
        J Clin Psychiatry. 2013; 74: e03
        • Mikail S.F.
        • von Baeyer C.L.
        Pain, somatic focus, and emotional adjustment in children of chronic headache sufferers and controls.
        Soc Sci Med. 1990; 31: 51-59
        • Napadow V.
        • LaCount L.
        • Park K.
        • As-Sanie S.
        • Clauw D.J.
        • Harris R.E.
        Intrinsic brain connectivity in fibromyalgia is associated with chronic pain intensity.
        Arthritis Rheum. 2010; 62: 2545-2555
        • Oldfield R.C.
        The assessment and analysis of handedness: the Edinburgh inventory.
        Neuropsychologia. 1971; 9: 97-113
        • Otti A.
        • Guendel H.
        • Wohlschlager A.
        • Zimmer C.
        • Noll-Hussong M.
        Frequency shifts in the anterior default mode network and the salience network in chronic pain disorder.
        BMC Psychiatry. 2013; 13: 84
        • Pessoa L.
        • McKenna M.
        • Gutierrez E.
        • Ungerleider L.G.
        Neural processing of emotional faces requires attention.
        Proc Natl Acad Sci U S A. 2002; 99: 11458-11463
        • Petersen A.
        • Crockett L.
        • Richards M.
        • Boxer A.
        A self-report measure of pubertal status: reliability, validity, and initial norms.
        J Youth Adolesc. 1988; 17: 117-133
        • Piira T.
        • Pullukat R.
        Are the children of chronic pain patients more likely to develop pain?.
        Enfance. 2006; 58: 20-25
        • Rice J.P.
        • Reich T.
        • Bucholz K.K.
        • Neuman R.J.
        • Fishman R.
        • Rochberg N.
        • Hesselbrock V.M.
        • Nurnberger Jr., J.I.
        • Schuckit M.A.
        • Begleiter H.
        Comparison of direct interview and family history diagnoses of alcohol dependence.
        Alcohol Clin Exp Res. 1995; 19: 1018-1023
        • Rickard K.
        The occurrence of maladaptive health-related behaviors and teacher-rated conduct problems in children of chronic low back pain patients.
        J Behav Med. 1988; 11: 107-116
        • Rosenthal R.
        • Rosnow R.L.
        Essentials of Behavioral Research: Methods and Data Analysis.
        in: 2nd ed. McGraw-Hill, New York1991
        • Sava S.
        • Lebel A.A.
        • Leslie D.S.
        • Drosos A.
        • Berde C.
        • Becerra L.
        • Borsook D.
        Challenges of functional imaging research of pain in children.
        Mol Pain. 2009; 5: 30
        • Schweinhardt P.
        • Kalk N.
        • Wartolowska K.
        • Chessell I.
        • Wordsworth P.
        • Tracey I.
        Investigation into the neural correlates of emotional augmentation of clinical pain.
        Neuroimage. 2008; 40: 759-766
        • 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
        • Sherman A.L.
        • Bruehl S.
        • Smith C.A.
        • Walker L.S.
        Individual and additive effects of mothers' and fathers' chronic pain on health outcomes in young adults with a childhood history of functional abdominal pain.
        J Pediatr Psychol. 2013; 38: 365-375
        • Simons L.E.
        • Pielech M.
        • Erpelding N.
        • Linnman C.
        • Moulton E.
        • Sava S.
        • Lebel A.
        • Serrano P.
        • Sethna N.
        • Berde C.
        • Becerra L.
        • Borsook D.
        The responsive amygdala: treatment-induced alterations in functional connectivity in pediatric complex regional pain syndrome.
        Pain. 2014; 155: 1727-1742
        • Stanford E.A.
        • Chambers C.T.
        • Biesanz J.C.
        • Chen E.
        The frequency, trajectories and predictors of adolescent recurrent pain: a population-based approach.
        Pain. 2008; 138: 11-21
        • Stoltenberg S.F.
        • Mudd S.A.
        • Blow F.C.
        • Hill E.M.
        Evaluating measures of family history of alcoholism: density versus dichotomy.
        Addiction. 1998; 93: 1511-1520
        • Tagliazucchi E.
        • Balenzuela P.
        • Fraiman D.
        • Chialvo D.R.
        Brain resting state is disrupted in chronic back pain patients.
        Neurosci Lett. 2010; 485: 26-31
        • Talairach J.
        • Tournoux P.
        Coplanar Stereotaxic Atlas of the Human Brain. Three-Dimensional Proportional System: An Approach to Cerebral Imaging.
        Thieme, New York1988
        • Thomas K.M.
        • Drevets W.C.
        • Whalen P.J.
        • Eccard C.H.
        • Dahl R.E.
        • Ryan N.D.
        • Casey B.J.
        Amygdala response to facial expressions in children and adults.
        Biol Psychiatry. 2001; 49: 309-316
        • Tottenham N.
        • Tanaka J.W.
        • Leon A.C.
        • McCarry T.
        • Nurse M.
        • Hare T.A.
        • Marcus D.J.
        • Westerlund A.
        • Casey B.J.
        • Nelson C.
        The NimStim set of facial expressions: judgments from untrained research participants.
        Psychiatry Res. 2009; 168: 242-249
        • Vehof J.
        • Zavos H.M.
        • Lachance G.
        • Hammond C.J.
        • Williams F.M.
        Shared genetic factors underlie chronic pain syndromes.
        Pain. 2014; 155: 1562-1568
        • Verhaak P.F.
        • Kerssens J.J.
        • Dekker J.
        • Sorbi M.J.
        • Bensing J.M.
        Prevalence of chronic benign pain disorder among adults: a review of the literature.
        Pain. 1998; 77: 231-239
        • Von Korff M.
        • Crane P.
        • Lane M.
        • Miglioretti D.L.
        • Simon G.
        • Saunders K.
        • Stang P.
        • Brandenburg N.
        • Kessler R.
        Chronic spinal pain and physical-mental comorbidity in the United States: results from the national comorbidity survey replication.
        Pain. 2005; 113: 331-339
        • Wechsler D.
        Wechsler Abbreviated Scale of Intelligence.
        Psychological Corporation, San Antonio, TX1999
        • Weissman-Fogel I.
        • Moayedi M.
        • Tenenbaum H.C.
        • Goldberg M.B.
        • Freeman B.V.
        • Davis K.D.
        Abnormal cortical activity in patients with temporomandibular disorder evoked by cognitive and emotional tasks.
        Pain. 2011; 152: 384-396
        • Wolfson A.R.
        • Carskadon M.A.
        Sleep schedules and daytime functioning in adolescents.
        Child Dev. 1998; 69: 875-887
        • Zautra A.J.
        • Fasman R.
        • Reich J.W.
        • Harakas P.
        • Johnson L.M.
        • Olmsted M.E.
        • Davis M.C.
        Fibromyalgia: evidence for deficits in positive affect regulation.
        Psychosom Med. 2005; 67: 147-155
        • Zautra A.J.
        • Johnson L.M.
        • Davis M.C.
        Positive affect as a source of resilience for women in chronic pain.
        J Consult Clin Psychol. 2005; 73: 212-220