Inflammatory Genes and Psychological Factors Predict Induced Shoulder Pain Phenotype

Abstract

Purpose 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 pre-clinical shoulder pain phenotypes. Methods An exercise-induced shoulder injury model was used, and a priori selected genetic (IL1B, TNF/LTA region, IL6 single nucleotide polymorphisms, SNPs) and psychological (anxiety, depressive symptoms, pain catastrophizing, fear of pain, kinesiophobia) factors were included as the predictors of interest. The phenotypes were pain intensity (5-day average and peak reported on numerical rating scale), upper-extremity disability (5-day average and peak reported on the QuickDASH instrument), and duration of shoulder pain (in days). 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 depressive 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. Conclusion 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.

Biopsychosocial influence on shoulder pain

“…Participants were recruited into a preclinical exercise-induced shoulder injury (EISI) or clinical POSP cohort as appropriate. The EISI cohort has been described in our previous preclinical studies, 19,20 while this study is the first to report postoperative outcomes from the POSP cohort.…”

“…Genetic and psychological factors that comprised the risk subgroups were identified in an a priori manner based on the results from our previous preclinical studies. 19,20 …”

“…Fear of pain and pain catastrophizing consistently interacted with genes in our previous studies 19,20 and were included as psychological components of the risk subgroups. Fear of pain was assessed with the Fear of Pain Questionnaire (FPQ), a 30-item instrument that measures fear of specific situations that normally produce pain.…”

“…19,20 We selected a priori candidate genes known to be involved in pain modulation (eg, COMT and AVPR1A ) or proinflammatory (eg, TNF/LTA and IL1B ) responses and psychological constructs (eg, fear of pain and pain catastrophizing) that are established precursors to chronic pain conditions. Our preclinical findings identified multiple interactions between genes and psychological factors that improved prediction of exercise-induced shoulder pain beyond each individual factor.…”

“…Our preclinical findings identified multiple interactions between genes and psychological factors that improved prediction of exercise-induced shoulder pain beyond each individual factor. 19,20 These findings spurred interest in risk subgroups comprised genetic and psychological factors to determine the clinical relevance of these preclinical findings. Previous studies were completed in this preclinical model because it allowed for controlled muscle injury to the rotator cuff, which is a frequent target for shoulder surgery.…”