Advertisement

Biopsychosocial Influence on Exercise-Induced Injury: Genetic and Psychological Combinations Are Predictive of Shoulder Pain Phenotypes

      Abstract

      Chronic pain is influenced by biological, psychological, social, and cultural factors. The current study investigated potential roles for combinations of genetic and psychological factors in the development and/or maintenance of chronic musculoskeletal pain. An exercise-induced shoulder injury model was used, and a priori selected genetic (ADRB2, COMT, OPRM1, AVPR1 A, GCH1, and KCNS1) and psychological (anxiety, depressive symptoms, pain catastrophizing, fear of pain, and kinesiophobia) factors were included as predictors. Pain phenotypes were shoulder pain intensity (5-day average and peak reported on numerical rating scale), upper extremity disability (5-day average and peak reported on the QuickDASH), and shoulder pain duration (in days). After controlling for age, sex, and race, the genetic and psychological predictors were entered as main effects and interaction terms in separate regression models for the different pain phenotypes. Results from the recruited cohort (N = 190) indicated strong statistical evidence for interactions between the COMT diplotype and 1) pain catastrophizing for 5-day average upper extremity disability and 2) depressive symptoms for pain duration. There was moderate statistical evidence for interactions for other shoulder pain phenotypes between additional genes (ADRB2, AVPR1 A, and KCNS1) and depressive symptoms, pain catastrophizing, or kinesiophobia. These findings confirm the importance of the combined predictive ability of COMT with psychological distress and reveal other novel combinations of genetic and psychological factors that may merit additional investigation in other pain cohorts.

      Perspective

      Interactions between genetic and psychological factors were investigated as predictors of different exercise-induced shoulder pain phenotypes. The strongest statistical evidence was for interactions between the COMT diplotype and pain catastrophizing (for upper extremity disability) or depressive symptoms (for pain duration). Other novel genetic and psychological combinations were identified that may merit further investigation.

      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

        • Albaret M.C.
        • Munoz Sastre M.T.
        • Cottencin A.
        • Mullet E.
        The Fear of Pain questionnaire: Factor structure in samples of young, middle-aged and elderly European people.
        Eur J Pain. 2004; 8: 273-281
        • Belfer I.
        • Wu T.
        • Kingman A.
        • Krishnaraju R.K.
        • Goldman D.
        • Max M.B.
        Candidate gene studies of human pain mechanisms: Methods for optimizing choice of polymorphisms and sample size.
        Anesthesiology. 2004; 100: 1562-1572
        • Bishop M.D.
        • Horn M.E.
        • George S.Z.
        Exercise-induced pain intensity predicted by pre-exercise fear of pain and pain sensitivity.
        Clin J Pain. 2011; 27: 398-404
        • Bishop M.D.
        • Horn M.E.
        • George S.Z.
        • Robinson M.E.
        Self-reported pain and disability outcomes from an endogenous model of muscular back pain.
        BMC Musculoskelet Disord. 2011; 12: 35
        • Campbell C.M.
        • Edwards R.R.
        • Carmona C.
        • Uhart M.
        • Wand G.
        • Carteret A.
        • Kim Y.K.
        • Frost J.
        • Campbell J.N.
        Polymorphisms in the GTP cyclohydrolase gene (GCH1) are associated with ratings of capsaicin pain.
        Pain. 2009; 141: 114-118
        • Clarkson P.M.
        • Hubal M.J.
        Exercise-induced muscle damage in humans.
        Am J Phys Med Rehabil. 2002; 81: S52-S69
        • Costigan M.
        • Belfer I.
        • Griffin R.S.
        • Dai F.
        • Barrett L.B.
        • Coppola G.
        • Wu T.
        • Kiselycznyk C.
        • Poddar M.
        • Lu Y.
        • Diatchenko L.
        • Smith S.
        • Cobos E.J.
        • Zaykin D.
        • Allchorne A.
        • Gershon E.
        • Livneh J.
        • Shen P.H.
        • Nikolajsen L.
        • Karppinen J.
        • Männikkö M.
        • Kelempisioti A.
        • Goldman D.
        • Maixner W.
        • Geschwind D.H.
        • Max M.B.
        • Seltzer Z.
        • Woolf C.J.
        Multiple chronic pain states are associated with a common amino acid-changing allele in KCNS1.
        Brain. 2010; 133: 2519-2527
        • Desmeules J.
        • Piguet V.
        • Besson M.
        • Chabert J.
        • Rapiti E.
        • Rebsamen M.
        • Rossier M.F.
        • Curtin F.
        • Dayer P.
        • Cedraschi C.
        Psychological distress in fibromyalgia patients: A role for catechol-O-methyl-transferase Val158met polymorphism.
        Health Psychol. 2012; 31: 242-249
        • Diatchenko L.
        • Anderson A.D.
        • Slade G.D.
        • Fillingim R.B.
        • Shabalina S.A.
        • Higgins T.J.
        • Sama S.
        • Belfer I.
        • Goldman D.
        • Max M.B.
        • Weir B.S.
        • Maixner W.
        Three major haplotypes of the beta2 adrenergic receptor define psychological profile, blood pressure, and the risk for development of a common musculoskeletal pain disorder.
        Am J Med Genet B Neuropsychiatr Genet. 2006; 141B: 449-462
        • Diatchenko L.
        • Nackley A.G.
        • Slade G.D.
        • Bhalang K.
        • Belfer I.
        • Max M.B.
        • Goldman D.
        • Maixner W.
        Catechol-O-methyltransferase gene polymorphisms are associated with multiple pain-evoking stimuli.
        Pain. 2006; 125: 216-224
        • Diatchenko L.
        • Nackley A.G.
        • Slade G.D.
        • Fillingim R.B.
        • Maixner W.
        Idiopathic pain disorders—Pathways of vulnerability.
        Pain. 2006; 123: 226-230
        • Diatchenko L.
        • Slade G.D.
        • Nackley A.G.
        • Bhalang K.
        • Sigurdsson A.
        • Belfer I.
        • Goldman D.
        • Xu K.
        • Shabalina S.A.
        • Shagin D.
        • Max M.B.
        • Makarov S.S.
        • Maixner W.
        Genetic basis for individual variations in pain perception and the development of a chronic pain condition.
        Hum Mol Genet. 2005; 14: 135-143
        • Fillingim R.B.
        • Kaplan L.
        • Staud R.
        • Ness T.J.
        • Glover T.L.
        • Campbell C.M.
        • Mogil J.S.
        • Wallace M.R.
        The a118g single nucleotide polymorphism of the ì-opioid receptor gene (OPRM1) is associated with pressure pain sensitivity in humans.
        J Pain. 2005; 6: 159-167
        • Finan P.H.
        • Zautra A.J.
        • Davis M.C.
        • Lemery-Chalfant K.
        • Covault J.
        • Tennen H.
        COMT moderates the relation of daily maladaptive coping and pain in fibromyalgia.
        Pain. 2011; 152: 300-307
        • George S.Z.
        • Dover G.C.
        • Fillingim R.B.
        Fear of pain influences outcomes after exercise-induced delayed onset muscle soreness at the shoulder.
        Clin J Pain. 2007; 23: 76-84
        • George S.Z.
        • Dover G.C.
        • Wallace M.R.
        • Sack B.K.
        • Herbstman D.M.
        • Aydog E.
        • Fillingim R.B.
        Biopsychosocial influence on exercise-induced delayed onset muscle soreness at the shoulder: Pain catastrophizing and catechol-O-methyltransferase (COMT) diplotype predict pain ratings.
        Clin J Pain. 2008; 24: 793-801
        • George S.Z.
        • Wallace M.R.
        • Wright T.W.
        • Moser M.W.
        • Greenfield III, W.H.
        • Sack B.K.
        • Herbstman D.M.
        • Fillingim R.B.
        Evidence for a biopsychosocial influence on shoulder pain: Pain catastrophizing and catechol-O-methyltransferase (COMT) diplotype predict clinical pain ratings.
        Pain. 2008; 136: 53-61
        • Goubert L.
        • Crombez G.
        • Van Damme S.
        • Vlaeyen J.W.
        • Bijttebier P.
        • Roelofs J.
        Confirmatory factor analysis of the Tampa Scale for Kinesiophobia: Invariant two-factor model across low back pain patients and fibromyalgia patients.
        Clin J Pain. 2004; 20: 103-110
        • Gummesson C.
        • Ward M.M.
        • Atroshi I.
        The shortened disabilities of the arm, shoulder and hand questionnaire (QuickDASH): Validity and reliability based on responses within the full-length DASH.
        BMC Musculoskelet Disord. 2006; 7: 44
        • Hastie B.A.
        • Riley III, J.L.
        • Kaplan L.
        • Herrera D.G.
        • Campbell C.M.
        • Virtusio K.
        • Mogil J.S.
        • Wallace M.R.
        • Fillingim R.B.
        Ethnicity interacts with the OPRM1 gene in experimental pain sensitivity.
        Pain. 2012; 153: 1610-1619
        • Henker R.A.
        • Lewis A.
        • Dai F.
        • Lariviere W.R.
        • Meng L.
        • Gruen G.S.
        • Sereika S.M.
        • Pape H.
        • Tarkin I.S.
        • Gowda I.
        • Conley Y.P.
        The associations between OPRM1 and COMT genotypes and postoperative pain, opioid use, and opioid-induced sedation.
        Biol Res Nurs. 2012; 15: 309-317
        • Hirsh A.T.
        • George S.Z.
        • Riley III, J.L.
        • Robinson M.E.
        An evaluation of the measurement of pain catastrophizing by the Coping Strategies Questionnaire.
        Eur J Pain. 2007; 11: 75-81
        • Hocking L.J.
        • Smith B.H.
        • Jones G.T.
        • Reid D.M.
        • Strachan D.P.
        • Macfarlane G.J.
        Genetic variation in the beta2-adrenergic receptor but not catecholamine-O-methyltransferase predisposes to chronic pain: Results from the 1958 British Birth Cohort Study.
        Pain. 2010; 149: 143-151
        • Huang F.Y.
        • Chung H.
        • Kroenke K.
        • Delucchi K.L.
        • Spitzer R.L.
        Using the Patient Health Questionnaire-9 to measure depression among racially and ethnically diverse primary care patients.
        J Gen Intern Med. 2006; 21: 547-552
        • Hudak P.L.
        • Amadio P.C.
        • Bombardier C.
        Development of an upper extremity outcome measure: The DASH (disabilities of the arm, shoulder and hand) [corrected]. The Upper Extremity Collaborative Group (UECG).
        Am J Ind Med. 1996; 29: 602-608
        • IOM (Institute of Medicine)
        Relieving Pain in America: A Blueprint for Transforming Prevention, Care, Education, and Research.
        National Academies Press, Washington, DC2011
        • Kang E.H.
        • Yu B.H.
        Anxiety and beta-adrenergic receptor function in a normal population.
        Prog Neuropsychopharmacol Biol Psychiatry. 2005; 29: 733-737
        • Keller S.
        • Bann C.M.
        • Dodd S.L.
        • Schein J.
        • Mendoza T.R.
        • Cleeland C.S.
        Validity of the Brief Pain Inventory for use in documenting the outcomes of patients with noncancer pain.
        Clin J Pain. 2004; 20: 309-318
        • Kroenke K.
        • Spitzer R.L.
        The PHQ-9: A new depression diagnostic and severity measure.
        Psychiatr Ann. 2002; 32: 509-521
        • Leeuw M.
        • Goossens M.E.
        • Linton S.J.
        • Crombez G.
        • Boersma K.
        • Vlaeyen J.W.
        The fear-avoidance model of musculoskeletal pain: Current state of scientific evidence.
        J Behav Med. 2007; 30: 77-94
        • Linton S.J.
        • Shaw W.S.
        Impact of psychological factors in the experience of pain.
        Phys Ther. 2011; 91: 700-711
        • Lotsch J.
        • Geisslinger G.
        Relevance of frequent mu-opioid receptor polymorphisms for opioid activity in healthy volunteers.
        Pharmacogenomics J. 2006; 6: 200-210
        • McLean R.C.
        • Baird S.W.
        • Becker L.C.
        • Townsend S.N.
        • Gerstenblith G.
        • Kass D.A.
        • Tomaselli G.F.
        • Schulman S.P.
        Response to catecholamine stimulation of polymorphisms of the beta-1 and beta-2 adrenergic receptors.
        Am J Cardiol. 2012; 110: 1001-1007
        • McNeil D.W.
        • Rainwater A.J.
        Development of the Fear of Pain Questionnaire–III.
        J Behav Med. 1998; 21: 389-410
        • Mogil J.S.
        Pain genetics: Past, present and future.
        Trends Genet. 2012; 28: 258-266
        • Mogil J.S.
        • Sorge R.E.
        • LaCroix-Fralish M.L.
        • Smith S.B.
        • Fortin A.
        • Sotocinal S.G.
        • Ritchie J.
        • Austin J.S.
        • Schorscher-Petcu A.
        • Melmed K.
        • Czerminski J.
        • Bittong R.A.
        • Mokris J.B.
        • Neubert J.K.
        • Campbell C.M.
        • Edwards R.R.
        • Campbell J.N.
        • Crawley J.N.
        • Lariviere W.R.
        • Wallace M.R.
        • Sternberg W.F.
        • Balaban C.D.
        • Belfer I.
        • Fillingim R.B.
        Pain sensitivity and vasopressin analgesia are mediated by a gene-sex-environment interaction.
        Nat Neurosci. 2011; 14: 1569-1573
        • Moller A.T.
        • Jensen T.S.
        Pain and genes: Genetic contribution to pain variability, chronic pain and analgesic responses.
        Eur J Pain Suppl. 2010; 4: 197-201
        • Munafo M.R.
        • Stevenson J.
        Anxiety and surgical recovery. Reinterpreting the literature.
        J Psychosom Res. 2001; 51: 589-596
        • Osman A.
        • Breitenstein J.L.
        • Barrios F.X.
        • Gutierrez P.M.
        • Kopper B.A.
        The Fear of Pain Questionnaire-III: Further reliability and validity with nonclinical samples.
        J Behav Med. 2002; 25: 155-173
        • Parr J.J.
        • Borsa P.A.
        • Fillingim R.B.
        • Tillman M.D.
        • Manini T.M.
        • Gregory C.M.
        • George S.Z.
        Pain-related fear and catastrophizing predict pain intensity and disability independently using an induced muscle injury model.
        J Pain. 2012; 13: 370-378
        • Skouen J.S.
        • Smith A.J.
        • Warrington N.M.
        • O'Sullivan P.B.
        • McKenzie L.
        • Pennell C.E.
        • Straker L.M.
        Genetic variation in the beta-2 adrenergic receptor is associated with chronic musculoskeletal complaints in adolescents.
        Eur J Pain. 2012; 16: 1232-1242
        • Smith S.B.
        • Maixner D.W.
        • Greenspan J.D.
        • Dubner R.
        • Fillingim R.B.
        • Ohrbach R.
        • Knott C.
        • Slade G.D.
        • Bair E.
        • Gibson D.G.
        • Zaykin D.V.
        • Weir B.S.
        • Maixner W.
        • Diatchenko L.
        Potential genetic risk factors for chronic TMD: Genetic associations from the OPPERA case control study.
        J Pain. 2011; 12: T92-T101
        • Spielberger C.D.
        • Gorsuch R.L.
        • Lushene R.E.
        • Vagg P.R.
        • Jacobs G.A.
        Manual for the State and Trait Anxiety Inventory (Form Y).
        Consulting Psychologists Press, Palo Alto, CA1983
        • Sullivan M.J.L.
        • Bishop S.R.
        • Pivik J.
        The Pain Catastrophizing Scale: Development and validation.
        Psychol Assess. 1995; 7: 524-532
        • Tammimaki A.
        • Mannisto P.T.
        Catechol-O-methyltransferase gene polymorphism and chronic human pain: A systematic review and meta-analysis.
        Pharmacogenet Genomics. 2012; 22: 673-691
        • Van Damme S.
        • Crombez G.
        • Bijttebier P.
        • Goubert L.
        • Van Houdenhove B.
        A confirmatory factor analysis of the Pain Catastrophizing Scale: Invariant factor structure across clinical and non-clinical populations.
        Pain. 2002; 96: 319-324
        • Vaughn F.
        • Wichowski H.
        • Bosworth G.
        Does preoperative anxiety level predict postoperative pain?.
        AORN J. 2007; 85: 589-604
        • Woby S.R.
        • Roach N.K.
        • Urmston M.
        • Watson P.J.
        Psychometric properties of the TSK-11: A shortened version of the Tampa Scale for Kinesiophobia.
        Pain. 2005; 117: 137-144
        • Yu B.H.
        • Dimsdale J.E.
        • Mills P.J.
        Psychological states and lymphocyte beta-adrenergic receptor responsiveness.
        Neuropsychopharmacology. 1999; 21: 147-152
        • Zubieta J.K.
        • Heitzeg M.M.
        • Smith Y.R.
        • Bueller J.A.
        • Xu K.
        • Xu Y.
        • Koeppe R.A.
        • Stohler C.S.
        • Goldman D.
        COMT val158met genotype affects mu-opioid neurotransmitter responses to a pain stressor.
        Science. 2003; 21: 1240-1243