title: Inflammatory genes and psychological factors predict induced shoulder pain phenotype.
abstract: OBJECTIVE
  The pain experience has multiple influences, but little is known about how specific biological and psychological factors interact to influence pain responses. The current study investigated the combined influences of genetic (pro-inflammatory) and psychological factors on several preclinical shoulder pain phenotypes.
  
  
  METHODS
  An exercise-induced shoulder injury model was used, and a priori selected genetic (IL1B, TNF/LTA region, and IL6 single nucleotide polymorphisms (SNP)) and psychological (anxiety, depression symptoms, pain catastrophizing, fear of pain, and kinesiophobia) factors were included as the predictors of interest. The phenotypes were pain intensity (5-d average and peak reported on numerical rating scale), upper extremity disability (5-d average and peak reported on the Quick Disabilities of the Arm, Shoulder and Hand instrument), and duration of shoulder pain (d).
  
  
  RESULTS
  After controlling for age, sex, and race, the genetic and psychological predictors were entered separately as main effects and interaction terms in regression models for each pain phenotype. Results from the recruited cohort (n = 190) indicated strong statistical evidence for the interactions between 1) TNF/LTA SNP rs2229094 and depression symptoms for average pain intensity and duration and 2) IL1B two SNP diplotype and kinesiophobia for average shoulder pain intensity. Moderate statistical evidence for prediction of additional shoulder pain phenotypes included interactions of kinesiophobia, fear of pain, or depressive symptoms with TNF/LTA rs2229094 and IL1B.
  
  
  CONCLUSIONS
  These findings support the combined predictive ability of specific genetic and psychological factors for shoulder pain phenotypes by revealing novel combinations that may merit further investigation in clinical cohorts to determine their involvement in the transition from acute to chronic pain conditions.
authors.affiliation: 1Department of Physical Therapy, Center for Pain Research and Behavioral Health, University of Florida, Gainesville, FL; 2Department of Sports Medicine and Nutrition, University of Pittsburgh, Pittsburgh, PA; 3Department of Molecular Genetics and Microbiology, Center for Epigenetics, Genetics Institute, University of Florida, Gainesville, FL; 4Department of Biostatistics, University of Florida, Gainesville, FL; 5Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL; and 6Department of Community Dentistry and Behavioral Science, University of Florida, Gainesville, FL.
authors.forename: Steven Z
authors.initials: SZ
authors.lastname: George
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Parr
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Wallace
authors.forename: Samuel S
authors.initials: SS
authors.lastname: Wu
authors.forename: Paul A
authors.initials: PA
authors.lastname: Borsa
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Dai
authors.forename: Roger B
authors.initials: RB
authors.lastname: Fillingim
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D053583:Interleukin-1beta / Q000235:genetics; D008233:Lymphotoxin-alpha / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012782:Shoulder / Q000503:physiopathology; D000070599:Shoulder Injuries; D020069:Shoulder Pain / Q000235:genetics* / Q000523:psychology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D055815:Young Adult
chemical_list: C508585:IL1B protein, human; D053583:Interleukin-1beta; D008233:Lymphotoxin-alpha; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha